tag:blogger.com,1999:blog-15545038743134614332024-03-13T03:06:52.627+02:00Protein Evolution and Other MusingsBlogging about my research on protein evolution and other stuff that interests me!Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.comBlogger36125tag:blogger.com,1999:blog-1554503874313461433.post-15012920897394316332015-02-12T14:28:00.000+02:002015-02-12T14:28:16.708+02:00post doc job opportunity on ribosome biochemistry!<div dir="ltr" style="text-align: left;" trbidi="on">
It's been sooooo long since I blogged, I'm actually ashamed to come back and post anything now! There is probably some proper term for that like "bloggers' guilt." Aha, yes, a quick google suggests this is a real term!<br />
<br />
Anyway, with one thing and another, life has been busy. And while I'd love to say I'm here to write about some exciting topic that's caught my interest (and there are many!), I'm actually back on Blogger to advertise a job opportunity to work with Vasili and I. This one:<br />
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Project description:<br />The focus of the project is biochemical analysis of Bacillus subtilis ribosome-associated stress factors. The project addresses questions generated through bioinformatic analysis of ribosomal factors, and will comprise of a biochemical research programme backed up by a complementary set of microbiological and structural investigations. The position is co-financed by funds from Ragnar Söderberg and Carl Tryggers foundations.</div>
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Our laboratory uses a combination of experimental (in vitro biochemistry in a reconstituted translational system, <span class="caps">NGS</span>-based techniques for in vivo biochemistry, as well as microbiological techniques) and in silico (molecular evolution) approaches. We are currently supported by the Swedish Research Council, Ragnar Söderberg foundation, Kempe foundation, Carl Tryggers foundation, as well as Umeå University funds.</div>
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For further information please contact Dr. Vasili Hauryliuk, <a href="mailto:vasili.hauryliuk@umu.se" style="color: #085878;">vasili.hauryliuk@umu.se</a> or Dr. Gemma C. Atkinson, <a href="mailto:gemma.atkinson@umu.se" style="color: #085878;">gemma.atkinson@umu.se</a>. See also our web page: <a href="http://www.mims.umu.se/groups/vasili-hauryliuk.html" style="color: #085878;">http://www.mims.umu.se/groups/vasili-hauryliuk.html</a></div>
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A successful candidate should meet the following criteria:</div>
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Essential:<br />- Documented proficiency in biochemical assays<br />- Strong skills in experimental design and interpretation<br />- A high level of proficiency in written and spoken English, as well as scientific writing<br />- A strong publication record in international, peer reviewed journals<br />- An ability to work effectively independently and as a group<br />- A willingness to learn new techniques</div>
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Highly desired:<br />- Experience in ribosomal biochemistry / <span class="caps">RNA</span> biochemistry<br />- Experience in bacterial genetics, particularly Bacillus subtilis</div>
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Applications should be written in English, comprise of a cover letter, CV with a publication list and contact information of at least two referees. Documents should be in MS Word or <span class="caps">PDF</span> format and submitted electronically to Dr. Vasili Hauryliuk, <a href="mailto:vasili.hauryliuk@umu.se" style="color: #085878;">vasili.hauryliuk@umu.se</a>, or Dr. Gemma Atkinson,<a href="mailto:gemma.atkinson@umu.se" style="color: #085878;">gemma.atkinson@umu.se</a>. The position is available starting spring 2015 (negotiable). </div>
Please share with anyone who might be interested!</div>
Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-9553559541180689082012-03-30T15:41:00.000+03:002012-03-30T15:41:25.634+03:00Finding a new translation factor, and verifying it with help from my experimental friends<div dir="ltr" style="text-align: left;" trbidi="on">
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Joy of joys my most recent paper has just been published in Nucleic Acids Research!<br />
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<div class="cit">
<a href="http://www.blogger.com/goog_1831453707" title="Nucleic acids research.">Nucleic Acids Res.</a><a href="http://www.blogger.com/goog_1831453707"> 2012 Mar 28. [Epub ahead of print]</a></div>
<h1>
<a href="http://www.blogger.com/goog_1831453707"><span style="font-size: small;">Evolutionary
and genetic analyses of mitochondrial translation initiation factors
identify the missing mitochondrial IF3 in S. cerevisiae.</span></a></h1>
<div class="auths">
<a href="http://www.blogger.com/goog_1831453707">Atkinson GC</a><a href="http://www.blogger.com/goog_1831453707">, </a><a href="http://www.blogger.com/goog_1831453707">Kuzmenko A</a><a href="http://www.blogger.com/goog_1831453707">, </a><a href="http://www.blogger.com/goog_1831453707">Kamenski P</a><a href="http://www.blogger.com/goog_1831453707">, </a><a href="http://www.blogger.com/goog_1831453707">Vysokikh MY</a><a href="http://www.blogger.com/goog_1831453707">, </a><a href="http://www.blogger.com/goog_1831453707">Lakunina V</a><a href="http://www.blogger.com/goog_1831453707">, </a><a href="http://www.blogger.com/goog_1831453707">Tankov S</a><a href="http://www.blogger.com/goog_1831453707">, </a><a href="http://www.blogger.com/goog_1831453707">Smirnova E</a><a href="http://www.blogger.com/goog_1831453707">, </a><a href="http://www.blogger.com/goog_1831453707">Soosaar A</a><a href="http://www.blogger.com/goog_1831453707">, </a><a href="http://www.blogger.com/goog_1831453707">Tenson T</a><a href="http://www.blogger.com/goog_1831453707">, </a><a href="http://www.blogger.com/goog_1831453707">Hauryliuk V</a><a href="http://nar.oxfordjournals.org/content/early/2012/03/28/nar.gks272.short">.</a></div>
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I'll give a little bit of background to the paper. I actually <a href="http://proteinevolution.fieldofscience.com/2011/09/molecular-biology-is-missing-trick-by.html">alluded to it last year</a> when we were in the early stages of writing up. <br />
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It started with these papers by <a href="http://www.sciencedirect.com/science/article/pii/S1097276507008003">Gaur et al</a> and <a href="http://www.pnas.org/content/108/10/3918.full">Yassin et al</a>, which claim that an insertion in mitochondrial initiation factor mIF2 evolved to compensate for a total lack of IF1 in mitochondria, which is universal in bacteria. This idea is really cute, and in fact they found that bovine mIF2 compensates for a lack of IF2+IF1 in <i>E. coli</i>. In addition, cryo-EM structures suggest the insertion occupies an overlapping site of the ribosome as IF1 does. However, I made an alignment of mIF2 from a broad distribution of eukaryotes and found there's a significant flaw with this hypothesis: mIF1 is absent in all eukaryotes, but the conserved insertion is only present in vertebrates. So somehow most eukaryotes through most of their evolutionary history have managed just fine without IF1 or the mIF2 insertion. This is a really nice example of how you really should do the comparative genomics of you want to make such sweeping claims as X evolved to replace Y. Here's the pic I made for my older blog post:<br />
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<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: 0px; margin-right: 0px; text-align: left;"><tbody>
<tr><td style="text-align: center;"><a href="http://3.bp.blogspot.com/-bhgjBtlGo3I/TnnWF5yK_lI/AAAAAAAAAMc/R4hJnKjBXyg/s1600/rainbowtree_2.png" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="176" src="http://3.bp.blogspot.com/-bhgjBtlGo3I/TnnWF5yK_lI/AAAAAAAAAMc/R4hJnKjBXyg/s640/rainbowtree_2.png" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Just replace "protein 1" with IF2 and "protein 2" with IF1. Simple! The point is, if you only look at humans and bacteria, you may jump to a conclusion that isn't supported when you sample broadly across taxa.</td></tr>
</tbody></table>
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My partner in life and crime, <a href="http://stringentresponse.blogspot.com/">Vasili</a> and I were thinking of writing up a teeny tiny paper about this, but then I started checking out more mitochondrial initiation factors... <br />
<br />
Most eukaryotes carry have an orthologue of mitochondrial mIF3, but a homologue had never been found in <i>Saccharomyces cerevisiae</i>. Considering how important IF3 is for bacterial translation, and also how human mIF3 is associated with Parkinson's disease, it was a real bummer that this wasn't present in the yeast mitochondrial system. Well, actually, people just weren't looking hard enough. mIF3 is a small protein with a very biased amino acid content, so if just searching with BlastP, you only pick up a few of the most closely related sequences. I tried the more sensitive PSI-Blast and found an <i>S. cerevisiae</i> homolog called Aim23p. Aim23p was known to be a mitochondrial protein, but its function had not been predicted. Phylogenetic analysis confirmed Aim23p is the orthologue of mIF3. Cool! So our teeny tiny paper suddenly got more substantial.<br />
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<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: 0px; margin-right: 0px; text-align: left;"><tbody>
<tr><td style="text-align: center;"><a href="http://1.bp.blogspot.com/-WyAe2HmTRpk/T3Wl_UmQMiI/AAAAAAAAAPQ/y_7qZE6nZSg/s1600/if3.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="356" src="http://1.bp.blogspot.com/-WyAe2HmTRpk/T3Wl_UmQMiI/AAAAAAAAAPQ/y_7qZE6nZSg/s640/if3.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">The two domains of mIF3. The yellow sites are those that are strongly conserved between mIF3 and Aim23p. They are mainly internal, probably important for stabilising the structure. The outer faces are more variable, possibly reflecting lineage-specific evolution of inter-molecular interactions.</td></tr>
</tbody></table>
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But the really cool stuff happened when we got our friends and collaborators from the lab of Piotr Kamenski in Moscow on board. Piotr's group showed that a knock-out of Aim23p can be complemented by <i>Schizosaccharomyces pombe </i>mIF3, strongly suggesting that Aim23 is the functional equivalent of mIF3 as well as the evolutionary orthologue.<br />
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I'm really happy about the results of this paper. It's a great feeling to predict something <i>in silico</i> that gets verified <i>in vivo</i>. Our next collaborative project with Piotr's group is a longer shot, but also bloody exciting, so fingers crossed!<br />
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<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Nucleic+Acids+Research&rft_id=info%3Adoi%2F10.1093%2Fnar%2Fgks272&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Evolutionary+and+genetic+analyses+of+mitochondrial+translation+initiation+factors+identify+the+missing+mitochondrial+IF3+in+S.+cerevisiae&rft.issn=0305-1048&rft.date=2012&rft.volume=&rft.issue=&rft.spage=&rft.epage=&rft.artnum=http%3A%2F%2Fwww.nar.oxfordjournals.org%2Fcgi%2Fdoi%2F10.1093%2Fnar%2Fgks272&rft.au=Atkinson%2C+G.&rft.au=Kuzmenko%2C+A.&rft.au=Kamenski%2C+P.&rft.au=Vysokikh%2C+M.&rft.au=Lakunina%2C+V.&rft.au=Tankov%2C+S.&rft.au=Smirnova%2C+E.&rft.au=Soosaar%2C+A.&rft.au=Tenson%2C+T.&rft.au=Hauryliuk%2C+V.&rfe_dat=bpr3.included=1;bpr3.tags=Biology">Atkinson, G., Kuzmenko, A., Kamenski, P., Vysokikh, M., Lakunina, V., Tankov, S., Smirnova, E., Soosaar, A., Tenson, T., & Hauryliuk, V. (2012). Evolutionary and genetic analyses of mitochondrial translation initiation factors identify the missing mitochondrial IF3 in S. cerevisiae <span style="font-style: italic;">Nucleic Acids Research</span> DOI: <a href="http://dx.doi.org/10.1093/nar/gks272" rev="review">10.1093/nar/gks272</a></span>
</div>
</div>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com4tag:blogger.com,1999:blog-1554503874313461433.post-82986824475365672932012-03-13T19:35:00.001+02:002012-03-16T21:59:39.095+02:00Switches and latches on the ribosome<span style="float: left; padding: 5px;"><a href="http://researchblogging.org/news/?p=3286"><img alt="This post was chosen as an Editor's Selection for ResearchBlogging.org" src="http://www.researchblogging.org/public/citation_icons/rb_editors-selection.png" style="border:0;"/></a></span><div dir="ltr" style="text-align: left;" trbidi="on">
<div style="text-align: justify;">
Call me a geek, but I'm a big fan of translational GTPases (trGTPases). They're essential factors for translation by the ribosome, highly conserved in all life and they're ancient. <i>Really</i> ancient. There were at least three (EF-Tu, IF2 and EF-G) in the ancestor of all life on earth. These have subsequently diversified through gene duplication and subfunctionalisation into the multiple trGTPase subfamilies that are known today.</div>
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Since a lot of my research is on trGTPase evolution, I was really interested to see this paper today in Nature Structural and Molecular Biology:<a href="http://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.2254.html"> A conserved proline switch on the ribosome facilitates the recruitment and binding of trGTPases. </a></div>
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In this paper, Wang <i>et al</i> have identified a universally conserved residue, Pro22 of <span class="annotation highlight-geneprot" data-related-id="entity-npg-biology-3" tabindex="0" title="Click on the name for more options">ribosomal protein L11</span> that switches conformation upon trGTPase EF-G binding, controlling the <span class="annotation highlight-geneprot" data-related-id="entity-npg-biology-3" tabindex="0" title="Click on the name for more options">L11</span> and <span class="annotation highlight-geneprot" data-related-id="entity-npg-biology-2" tabindex="0" title="Click on the name for more options">L12</span> protein interactions required for each peptide elongation cycle. They find that EF-G carries peptidyl-prolyl <i>cis</i>-<i>trans</i> isomerase (PPIase) activity<span class="annotation highlight-geneprot" data-related-id="entity-npg-biology-1" tabindex="0" title="Click on the name for more options">, </span>driving conformational switching of two adjacent prolines<span class="annotation highlight-geneprot" data-related-id="entity-npg-biology-1" tabindex="0" title="Click on the name for more options"> (PS22) </span>from a <i>trans</i> to <i>cis</i> orientation. <span class="annotation highlight-geneprot" data-related-id="entity-npg-biology-1" tabindex="0" title="Click on the name for more options"> </span></div>
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Most exciting for me is their claim that all known universal trGTPases contain an active PPIase center, and therefore that the <i>cis</i>-<i>trans</i> isomerization of PS22 is a universal event required for efficient turnover of trGTPases throughout the translation process. This is pretty cool. Hang on though... structures show that the potential PPIase motif is located in the cleft between domains G and V of EF-G, but the other trGTPases they mention in the paper (IF2, EF-Tu, EF-G, EF4 (LepA) and RF3) don't carry a domain homologous to EF-G's C-terminal domain V, so how does that work? Their structural figures of RF3, EF-Tu and LepA show their predictions of where the PPIase centre might be in these proteins. In each case, the centre is formed by residues of the GTPase (G) domain that correspond to the EF-G PPIase sites, plus nearby residues in the non-homologous C-terminal domains of these various trGTPases. So we would predict that if this is a universal mechanism, at least those residues of the G domain that are involved should be universally conserved. Unfortunately, an alignment of this region isn't presented in the paper, but fortunately I have one up my sleeve:</div>
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<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: 0px; margin-right: 0px; text-align: left;"><tbody>
<tr><td style="text-align: center;"><a href="http://2.bp.blogspot.com/-AX1gFylgK-8/T19HdHp7RQI/AAAAAAAAAPA/6IK1iwu8EVI/s1600/Screen+Shot+2012-03-13+at+15.10.50.png" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="400" src="http://2.bp.blogspot.com/-AX1gFylgK-8/T19HdHp7RQI/AAAAAAAAAPA/6IK1iwu8EVI/s400/Screen+Shot+2012-03-13+at+15.10.50.png" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">The region of the G domain containing sites proposed to be acting as a PPIase (yellow highlighting). These are just upstream of the G4 nucleotide binding motif (highlighted in turquoise). These are consensus sequences: the residue shown for each trGTPase in each position is the most common amino acid found there across all sequences of the subfamily. In essence, each sequence is an average of hundreds of sequences.</td></tr>
</tbody></table>
<div style="text-align: justify;">
The G domain is generally very well conserved across its length, with patches of universal conservation. However, the potential PPIase sites (yellow) are not universally conserved. The variability of these sites contrasts sharply with the nearby conserved G4 motif (one of the five motifs of the trGTPases - and in fact all GTPases - that coordinate the GTP/GDP nucleotides). It's disappointing, but this pattern of conservation doesn't really bear the hallmark of a universal mechanism. Indeed, Wang <i>et al</i> find that mutating the PPIase motif of EF-G has only a modest effect: a single turn of GTP hydrolysis was unaffected, but the multiple- turnover rates were inhibited by 15–40%. Similarly, mutation of PS22 did not completely abolish translation. </div>
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In fact, L11 is actually one of the few ribosomal proteins that is not essential for life, which makes L11 knock out strains useful molecular biological tools (for example <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917329/?tool=pubmed">this paper</a>). Therefore, the mechanistic details of this protein's role in translation, although very interesting of course, do not translate to an understanding of the core principles of how trGTPase work on the ribosome. </div>
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Are we really looking at something as concrete as a conserved "switch-and-latch" mechanism, or is PS22 just a trGTPase binding site with integral flexibility? Anyway, it's all interesting additional details of how trGTPases interact with the ribosome, and another plus: it got me blogging again after a long hiatus!<br />
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Reference: </div>
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Nature+structural+%26+molecular+biology&rft_id=info%3Apmid%2F22407015&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=A+conserved+proline+switch+on+the+ribosome+facilitates+the+recruitment+and+binding+of+trGTPases.&rft.issn=1545-9993&rft.date=2012&rft.volume=&rft.issue=&rft.spage=&rft.epage=&rft.artnum=&rft.au=Wang+L&rft.au=Yang+F&rft.au=Zhang+D&rft.au=Chen+Z&rft.au=Xu+RM&rft.au=Nierhaus+KH&rft.au=Gong+W&rft.au=Qin+Y&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Wang L, Yang F, Zhang D, Chen Z, Xu RM, Nierhaus KH, Gong W, & Qin Y (2012). A conserved proline switch on the ribosome facilitates the recruitment and binding of trGTPases. <span style="font-style: italic;">Nature Structural & Molecular Biology</span> PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/22407015" rev="review">22407015</a></span>
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</div>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com2tag:blogger.com,1999:blog-1554503874313461433.post-8192042457135235552012-01-04T14:21:00.000+02:002012-03-01T10:17:47.800+02:00PhD position available in Molecular Evolution!<div dir="ltr" style="text-align: left;" trbidi="on">
<b>**** EDIT </b>The position has now been filled and I'm no longer taking applications <b>****</b><br />
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<br />
Having got my Estonian Science Foundation grant funded recently, I have an open PhD position available! See below.<br />
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<br />
<div style="text-align: center;">
-----------------</div>
We are seeking a highly motivated PhD candidate to be supervised by Dr Gemma Atkinson within the group of Prof Tanel Tenson in the Institute of Technology, University of Tartu, Estonia.<br />
<br />
Dr Atkinson’s research addresses protein functional evolution, using bioinformatic approaches and primarily focusing on the ancient families of proteins involved in translation of mRNA to protein. Members of these families are often essential for life and predate the last common ancestor of all life on earth. Thus by studying these proteins we can gain understanding of the fundamental processes of life, and how these processes have evolved over billions of years.<br />
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The PhD project will take advantage of the thousands of whole genome sequences now available for the study of evolution of protein families from the origin of life to the present day. Work will involve sensitive sequence searching to identify the presence and absence of particular proteins across genomes, phylogenetic analyses to reconstruct their emergence and evolution, and sequence analyses to link domain- and site-specific patterns of amino acid substitution with molecular function. Specifically, the proposed PhD project will target the ABC superfamily of ATP-binding enzymes found in all domains of life. This superfamily comprises enigmatic proteins of diverse, and often unknown functions. Several ABC enzymes have recently been found to have important roles in regulation of translation such as ribosome recycling protein Rli1/ABCE1, yeast-specific elongation factor eEF3 and starvation response enzymes Gcn1 and Gcn20.<br />
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From the results of the PhD, it is expected that enzymes with novel roles in protein synthesis will come to light as interesting targets for subsequent experimental study. Dr Atkinson collaborates with the lab Dr Vasili Hauryliuk, also in Prof Tenson’s group, for biochemical and genetic validation of in silico results. If the candidate so wishes, there is an opportunity to gain practical lab experience in Dr Hauryliuk’s lab.<br />
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The candidate should have:<br />
<ul style="text-align: left;">
<li>a Masters degree in a biological or computational discipline</li>
<li>a strong interest in, and enthusiasm for molecular evolution</li>
<li>familiarity with basic sequence and phylogenetic analyses</li>
<li>experience in using a programming language such as Python, Perl, Java etc</li>
<li>fluency in spoken and written English</li>
</ul>
<br />
Estonia has a rich culture and beautiful natural environment, with unspoiled forests, meadows and coastlines. Enjoying warm summers and cold winters, the historical city of Tartu is the intellectual capital of Estonia, and its university is the leading research and development institution in the country. The Institute of Technology is a lively, modern centre for biological and technological research.<br />
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The PhD will be funded by a monthly stipend, with additional monies available for regular attendance at international conferences and workshops, and for visiting labs abroad. Information on funding is available by request.<br />
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Applications should contain:<br />
<ul style="text-align: left;">
<li>a full CV with detailed description of previous relevant experience</li>
<li>a statement of academic interests</li>
<li>an electronic version of the Masters thesis</li>
<li>the names and contact details of at least 2 referees </li>
</ul>
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The candidate is expected to start at the latest September 2012. Please send applications and informal enquiries to gemma.atkinson@ut.ee<br />
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Gemma Atkinson<br />
University of Tartu,<br />
Institute of Technology<br />
Nooruse 1, 50411 Tartu, Estonia<br />
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More information about the research of Dr Atkinson can be found here:<br />
http://lepo.it.da.ut.ee/~atkinson/gem_mac/gemma_c_atkinson.html<br />
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<br /></div>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-70526366321707192232011-12-22T16:43:00.000+02:002011-12-22T16:45:48.582+02:00My creative contributions to the Festive Tree of Life<div dir="ltr" style="text-align: left;" trbidi="on">
Last week I got a thick padded envelope from the Wellcome Trust. My colleagues were a bit surprised... I told them it was a grant, and well it kind of was, only not wads of cash, but lumps of modelling clay!<br />
<br />
As part of their <a href="http://wellcometrust.wordpress.com/2011/12/01/take-part-in-our-festive-tree-of-life/">Festive Tree of Life project</a>, the Wellcome trust sent out free packs of colourful modelling clay in the run up to the festive season. The idea is that you make science-inspired decorations and either hang them on their physical Christmas tree if you're somewhere in the vicinity, or post them on the <a href="http://www.flickr.com/groups/festivetreeoflife/pool/with/6542927247/">Festive Tree of Life Flicker page</a>.<br />
<br />
I had a fun afternoon the other day making my decorations. Here they are:<br />
<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="http://4.bp.blogspot.com/-9Yv4kFxqOcE/TvM5qA04u8I/AAAAAAAAAOM/jHW4mnWSmN0/s1600/DSC02726.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="233" src="http://4.bp.blogspot.com/-9Yv4kFxqOcE/TvM5qA04u8I/AAAAAAAAAOM/jHW4mnWSmN0/s320/DSC02726.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Mitochondrion</td></tr>
</tbody></table>
<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="http://3.bp.blogspot.com/-dfOxPd1B07M/TvM5sg9Qu_I/AAAAAAAAAOU/W_IdGB0TjiU/s1600/DSC02728.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="244" src="http://3.bp.blogspot.com/-dfOxPd1B07M/TvM5sg9Qu_I/AAAAAAAAAOU/W_IdGB0TjiU/s320/DSC02728.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Chloroplast</td></tr>
</tbody></table>
<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="http://3.bp.blogspot.com/-5XTXYpmHkdA/TvM5wBPeHYI/AAAAAAAAAOc/WXV0Q2DThPc/s1600/DSC02727.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="240" src="http://3.bp.blogspot.com/-5XTXYpmHkdA/TvM5wBPeHYI/AAAAAAAAAOc/WXV0Q2DThPc/s320/DSC02727.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Ribosome, with three tRNAs and EF-Tu. The pink thing is supposed to be mRNA, while the string is the nascent polypeptide chain coming out the exit tunnel... scale is overrated anyway.</td><td class="tr-caption" style="text-align: center;"></td></tr>
</tbody></table>
<br />
<br />
The clay started to dry up by the time I got to the ribosome, and got less sticky and more tricky to deal with. After a few hours, the tRNAs fell off, and the subunits have now almost dissociated. All of this in the absence of termination and ribosome recycling factors too!<br />
<br />
Happy holidays! <br />
<br /></div>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-35227448176620952692011-12-02T22:40:00.001+02:002011-12-09T22:00:39.970+02:00Bacterial genes in eukaryotes - function and phylogeny<div dir="ltr" style="text-align: left;" trbidi="on">
<div dir="ltr" style="text-align: left;" trbidi="on">
There have been a couple of interesting papers recently on those eukaryotic genes that are more closely related to bacterial, than archaeal homologues. Such proteins are often organellar (athough they may be encoded in the nucleus), having entered eukaryotes with the bacterial endosymbiosis event that gave rise to the mitochondrion (or the event that gave rise to the chloroplast in the case of plants).<br />
<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="http://2.bp.blogspot.com/-RJXnvAL18jg/TuIPEYNoSLI/AAAAAAAAAN8/1G505sLtr14/s1600/mt2.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="240" src="http://2.bp.blogspot.com/-RJXnvAL18jg/TuIPEYNoSLI/AAAAAAAAAN8/1G505sLtr14/s320/mt2.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Giant, glowing mitochondria in the Deutsches Museum, Munich</td></tr>
</tbody></table>
<br />
<br />
The first paper, published in GBE, considers humans alone: <br />
<br />
<a href="http://www.blogger.com/goog_1329887993">The human genome retains relics of its prokaryotic ancestry: human genes of archaebacterial and eubacterial origin exhibit remarkable differences.</a><br />
<a href="http://gbe.oxfordjournals.org/content/early/2011/07/26/gbe.evr073.abstract">David Alvarez-Ponce and James O. McInerney</a><br />
<br />
This paper tests whether human genes of different ancestries (bacterial versus archaeal) have different effects on phenotype, essentiality of the gene (as judged by lethality in mice), function, selective constraint, expression and position in protein-protein interaction network (PIN). Proteins were classified as bacteria- or archaea-like based on best hit scores in Blast searches.<br />
<br />
They found that human genes of archaeal ancestry, although fewer in number, tend to be have higher and broader expression levels, are more likely to be essential, are involved in core information processes, are under greater selection, and tend to be central in the PIN, as compared with bacteria-like genes.<br />
<br />
I don't think they mention whether the archaea-like genes they identified have (more distant) homologues in bacteria too... if they do, then we're likely looking at the characteristics of universal, usually essential, core information processing genes. Whether archaeal-like genes that have been lost in bacteria are just as central in eukaryotes as universal genes, it isn't clear.<br />
<br />
It's also not clear just how many of the bacteria-like genes are endosymbiotic in origin. 7,884 human genes were found to be bacteria-like, but the human mitochondrion is predicted to contain only 1000-1500 proteins. Of the remainder, while some are likely to be endosymbiotic in origin, but have acquired non-mitochondrial functions, an unknown proportion may actually be of archaeal ancestry, but have been lost in archaea, and so are actually nothing to do with mitchondria. As these proteins are not universally essential, it follows that they would have a less central role in the cell... maybe the two gene populations that are considered in this paper are more like essential for life versus non-essential for life. <br />
<br />
Anyway, it's a very interesting paper, particularly the finding that archaeal-like genes are less likely to be involved in inherited diseases. It's also surprising just how many genes did not have an identifiable homologue in either bacteria or archaea (58%).<br />
<br />
The second paper, published in MBE addresses the evolutionary history of mitochondrial genes from a broad distribution of eukaryotes: <br />
<br />
<a href="http://www.blogger.com/goog_1329887989">Rooting the eukaryotic tree with mitochondrial and bacterial proteins</a><br />
<a href="http://mbe.oxfordjournals.org/content/early/2011/12/01/molbev.msr295.short?rss=1">Romain Derelle and B. Franz Lang</a><br />
<br />
The idea here is that the endosymbiosis event happened more recently than the divergence of eukaryotes from archaea, and this can be exploited for rooting the eukaryotic tree of life with a less divergent outgroup. Usually eukaryotic phylogenies are made using archaea-like information processing genes, rooted with archaea. However, there is a problem of long branch attraction to the very distant outgroup. This is the phenomenon in molecular phylogenetics where fast evolving, and therefore long branched sequences that should be nested within the tree are pulled down to the base of the tree because of spurious similarities to the outgroup. Using mitochondrial genes to make trees rooted with bacteria theoretically reduces the distance to the outgroup and, therefore, the problem of LBA.<br />
<br />
The idea is very neat and I like it in principle. There are a couple of issues though that I think might not help the LBA problem, and in fact might exacerbate the problem.<br />
<br />
1. We don't know just how much more recently the mitochondrion was acquired after the divergence of eukaryotes from archaea. Some people might argue that this was the event was involved in the separation of the two lineages.<br />
2. Mitochondrial genes have a faster rate of evolution than their cytoplasmic counterparts. <br />
<br />
Still, its interesting to see the results of rooting the eukaryotic tree in this way. The paper doesn't use best hits as in the above paper, but specifically targets known mitochondrial and mitochondrially targeted genes, such as cytochromes and two of the three universal mitochondrial translational GTPases, mIF2 and mEF-Tu. The third, <a href="http://proteinevolution.fieldofscience.com/2010/11/evolution-of-elongation-factor-g.html">mEF-G</a> was likely excluded because it does not group with alpha-proteobacteria. Although... come to think of it, I don't see mEF-Tu or mIF2 grouping clearly with alphas in my trees... maybe EF-G was excluded because of its duplication early in eukaryotic evolution... though, mEF-Tu has also been duplicated in its history, and actually mEF-G1 is quite a conservative marker... anyway, this paper isn't about trGTPases specifically so I shouldn't drift off topic.<br />
<br />
So, the root. They find the root between monophyletic unikonts (opisthokonts and amoebozoa) and bikonts (other eukaryotes), supporting one of the most popular hypotheses. There seems to good statistical support for this topology using the Bayesian inference method, however, maximum likelihood support is only achieved with much filtering of the dataset. It's an interesting new take on rooting the eukaryotic tree, but not one that will convince everyone.<br />
<br />
As is so often the conclusion, we're just going to need more eukaryotic protist genomes!</div>
<b>Refs</b>
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Genome+biology+and+evolution&rft_id=info%3Apmid%2F21795752&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=The+human+genome+retains+relics+of+its+prokaryotic+ancestry%3A+human+genes+of+archaebacterial+and+eubacterial+origin+exhibit+remarkable+differences.&rft.issn=&rft.date=2011&rft.volume=3&rft.issue=&rft.spage=782&rft.epage=90&rft.artnum=&rft.au=Alvarez-Ponce+D&rft.au=McInerney+JO&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics"> </span><br />
<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Genome+biology+and+evolution&rft_id=info%3Apmid%2F21795752&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=The+human+genome+retains+relics+of+its+prokaryotic+ancestry%3A+human+genes+of+archaebacterial+and+eubacterial+origin+exhibit+remarkable+differences.&rft.issn=&rft.date=2011&rft.volume=3&rft.issue=&rft.spage=782&rft.epage=90&rft.artnum=&rft.au=Alvarez-Ponce+D&rft.au=McInerney+JO&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Alvarez-Ponce D, & McInerney JO (2011). The human genome retains relics of its prokaryotic ancestry: human genes of archaebacterial and eubacterial origin exhibit remarkable differences. <span style="font-style: italic;">Genome biology and evolution, 3</span>, 782-90 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/21795752" rev="review">21795752</a></span>
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Molecular+biology+and+evolution&rft_id=info%3Apmid%2F22135192&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Rooting+the+eukaryotic+tree+with+mitochondrial+and+bacterial+proteins.&rft.issn=0737-4038&rft.date=2011&rft.volume=&rft.issue=&rft.spage=&rft.epage=&rft.artnum=&rft.au=Derelle+R&rft.au=Lang+BF&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Derelle R, & Lang BF (2011). Rooting the eukaryotic tree with mitochondrial and bacterial proteins. <span style="font-style: italic;">Molecular biology and evolution</span> PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/22135192" rev="review">22135192</a></span>
</div>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com3tag:blogger.com,1999:blog-1554503874313461433.post-88727138203293858042011-10-31T15:18:00.001+02:002011-10-31T15:37:04.119+02:00Coevolution, from hummingbirds to proteins<div dir="ltr" style="text-align: left;" trbidi="on">
Coevolution (two or more biological objects evolving together) is a common feature of the evolutionary process on all levels from the molecular to the organismal. One of the most beautiful examples is that of hummingbirds and ornithophilous flowers. Hummingbirds feed on the nectar from the flowers, pollinating them in the process. In this mutually beneficial relationship, the plants have evolved flowers that attract the birds with colours that are conspicuous to the bird, and are shaped to perfectly accommodate the bird's beak. This coevolution has happened in a number of hummingbird/plant pairs.<br />
<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="http://upload.wikimedia.org/wikipedia/commons/thumb/4/46/Purple-throated_carib_hummingbird_feeding.jpg/220px-Purple-throated_carib_hummingbird_feeding.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="213" src="http://upload.wikimedia.org/wikipedia/commons/thumb/4/46/Purple-throated_carib_hummingbird_feeding.jpg/220px-Purple-throated_carib_hummingbird_feeding.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Pic from Wikipedia article on humming birds</td></tr>
</tbody></table>
<br />
For more information on hummingbird/plant coevolution, I direct you to the <a href="https://www.amherst.edu/people/facstaff/ejtemeles/selected_publications">publications of Ethan Temeles.</a> As usual though, this post will be about proteins, and not whole organisms... and it will include my own crude drawings as usual...<br />
<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="http://3.bp.blogspot.com/-RfZzSHmFs9I/Tqk2m4cksEI/AAAAAAAAAM4/64dkyr5ZeT8/s1600/coevolutionsites.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="223" src="http://3.bp.blogspot.com/-RfZzSHmFs9I/Tqk2m4cksEI/AAAAAAAAAM4/64dkyr5ZeT8/s320/coevolutionsites.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Fig 1. Ta-da! Hummingbird/plant coevolution is a nice analogy for protein receptor/ligand coevolution. Circles show residues directly involved in the interaction.</td></tr>
</tbody></table>
<div class="separator" style="clear: both; text-align: center;">
<a href="http://4.bp.blogspot.com/-XUTS6K58de8/Tqk2EKJ4CNI/AAAAAAAAAMw/spuHvoj3YaQ/s1600/coevolutionsites.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><br />
</a></div>
<div class="separator" style="clear: both; text-align: center;">
<a href="http://2.bp.blogspot.com/-NQO4Q3nVU7Y/Tqk1-9CUsMI/AAAAAAAAAMo/5S5qinKbOLQ/s1600/bindinginterfaces.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><br />
</a></div>
At the molecular level, an example of coevolution is in the establishment of receptor-ligand interactions (Fig 1). The receptor protein binding site has evolved in concert with the binding site of the ligand. In Fig 1, variation of the yelow residues in the receptor is correlated with that of the green residues in the ligand. The yellow sites are close together in the structure, but not necessarily neighboring in the sequence. For example, the amino acid sequence backbone of these imaginary proteins might be arranged like this:<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="http://3.bp.blogspot.com/-rdHTzeCNlfI/TqlR9fVF21I/AAAAAAAAANA/tHASagRKB7Y/s1600/coevolutionsites_internal.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="222" src="http://3.bp.blogspot.com/-rdHTzeCNlfI/TqlR9fVF21I/AAAAAAAAANA/tHASagRKB7Y/s320/coevolutionsites_internal.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Fig 2. Black lines show the amino acid sequence of the protein, within its structural density.</td></tr>
</tbody></table>
<br />
<br />
Thus, if
the structure of the binding interface is known, it's possible to predict
candidate coevolving sites. However from the sequence alone, it's not
so straightforward. <br />
<br />
As discussed in a recent paper of <a href="http://mbe.oxfordjournals.org/content/27/5/1181.abstract">Gloor et al in MBE</a> (and references within), there are two explanations for how covarying positions come to be (and these are actually the extremes of the distribution of possible mutational effects):<br />
<br />
1. Suppressor mutations. These arise when a mutation with a
deleterious phenotype is suppressed by another mutation at a different
position.<br />
2. Covarions. These are cases when both the original residue and the mutated residue are functionally compatible, but mutation alters the spectrum of amino acids possible at another location.<br />
<br />
Covarying sites may occur in the
same protein or in different proteins (Figs 3-4). <br />
<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="http://3.bp.blogspot.com/-Q_p5Lp26uBI/TqlbfzKCuGI/AAAAAAAAANY/nLJEA1b6dQo/s1600/coevolutionsites_focus.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="180" src="http://3.bp.blogspot.com/-Q_p5Lp26uBI/TqlbfzKCuGI/AAAAAAAAANY/nLJEA1b6dQo/s200/coevolutionsites_focus.jpg" width="200" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Fig 3. Stars show between-protein correlated mutations at two interaction sites</td><td class="tr-caption" style="text-align: center;"><br /></td></tr>
</tbody></table>
<br />
In between-protein coevolution, green sites coevolve with yellow sites in our example. But there is also within-protein coevolution among yellow site residues and among green site residues. Imagine for instance a change of green residue that multiple yellow resides interact with at different times (Fig 4). Or perhaps the middle yellow starred residue in Fig 4 mutating and causing different constraints in what residues the neighboring yellow sites can mutate to. Either way, the three yellow sites will covary. Remember that those sites are far away from each other in the sequence. So by showing that these sites co-vary, we can predict that they are functionally related, even if we don't have a structure<br />
<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="http://1.bp.blogspot.com/-fG8oYd_1PL8/Tqls5aYhwiI/AAAAAAAAANg/dsCC1M3dYPo/s1600/coevolutionsites_focus2.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="170" src="http://1.bp.blogspot.com/-fG8oYd_1PL8/Tqls5aYhwiI/AAAAAAAAANg/dsCC1M3dYPo/s200/coevolutionsites_focus2.jpg" width="200" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Fig 4. Correlated mutations can also occur within one protein </td></tr>
</tbody></table>
<br />
Prediction of co-evolving sites can be useful for understanding cases when binding site residues are unconserved in a multiple sequence alignment. It can also be useful for predicting intermolecular interaction sites, and allosteric sites (for example <a href="http://www.jbc.org/content/281/26/18184.abstract">Chen et al., 2006</a>). An allosteric site can remotely affect the evolutionary pressures on a
distant site by affecting the structural orientation of the protein (Fig 5).<br />
<br />
<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="http://1.bp.blogspot.com/-OlSdDRNjjMY/TqmbLM_gxiI/AAAAAAAAANo/YAbQlAf7D7I/s1600/coevolutionsites_focus3.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="217" src="http://1.bp.blogspot.com/-OlSdDRNjjMY/TqmbLM_gxiI/AAAAAAAAANo/YAbQlAf7D7I/s320/coevolutionsites_focus3.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Fig 5. Correlated mutations among binding site residues and an allosteric site.</td></tr>
</tbody></table>
<br />
<br />
Prediction of covarying sites is challenging, not only because they may not always be clustered together in sequence and structure, but because covariation is a combined result of structural and functional
constraints and background noise from shared phylogenetic
ancestry and random processes.<br />
<br />
There are two classes of methods for predicting covarying sites: tree-aware and tree-unaware. Tree aware methods search for sites whose covariation can not be explained by phylogenetic relationships, while tree-unaware methods ignore phylogenetic relationships, instead searching for covarying sites with the strongest signal. The two classes of methods are discussed in <a href="http://www.biomedcentral.com/1471-2148/8/327">Caporase et al (2008)</a>, in which it is concluded that tree-unaware methods perform as well as tree-unaware.<br />
<br />
Using a tree-unaware method, <a href="http://mbe.oxfordjournals.org/content/27/5/1181.abstract">Gloor et al. (2010)</a> examine covariation in phosphoglyerate kinase evolution. They identify nonconserved sites that covary, and through mutagenesis show that the sites are important for function and epistatic to each other (mutation in one affects the function of the other). They find that covarying positions
are just as as diverse within and between clades as are noncovarying positions, and suggest that most covarying positions arise from processes more like the covarion model, than the suppression mutation model.<br />
<br />
The importance of covariation in sequence evolution is of interest to people like myself who use patterns of sequence variation to predict protein function. In studying molecular evolution of function, we largely rely on the assumption that the most functionally important positions are those that are conserved over time. Although this is generally the case, it seems that some important sites that are able to covary may slip through the net.<br />
<br />
Recently, I've been experimenting with the tree-unaware code of<a href="http://bioinformatics.oxfordjournals.org/content/24/3/333.abstract"> Dunn et al., (2008)</a> to find covarying sites Preliminary results, based on the RelA family are... confusing. Residues that would be predicted to be interacting from the structure are not flagged up as covarying, while there are many pairs of predicted covaring sites that are physically distant and don't seem likely to be allostric sites from the structure. It seems like as with many real-life case studies, real biology is a little bit more complicated than naive sketches like mine would have you believe! Oh well, time to delve a little deeper into the data set... <br />
<br />
References and further reading:<br />
<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=BMC+Evolutionary+Biology&rft_id=info%3Adoi%2F10.1186%2F1471-2148-8-327&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Detecting+coevolution+without+phylogenetic+trees%3F+Tree-ignorant+metrics+of+coevolution+perform+as+well+as+tree-aware+metrics&rft.issn=1471-2148&rft.date=2008&rft.volume=8&rft.issue=1&rft.spage=327&rft.epage=&rft.artnum=http%3A%2F%2Fwww.biomedcentral.com%2F1471-2148%2F8%2F327&rft.au=Caporaso%2C+J.&rft.au=Smit%2C+S.&rft.au=Easton%2C+B.&rft.au=Hunter%2C+L.&rft.au=Huttley%2C+G.&rft.au=Knight%2C+R.&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Caporaso, J., Smit, S., Easton, B., Hunter, L., Huttley, G., & Knight, R. (2008). Detecting coevolution without phylogenetic trees? Tree-ignorant metrics of coevolution perform as well as tree-aware metrics <span style="font-style: italic;">BMC Evolutionary Biology, 8</span> (1) DOI: <a href="http://dx.doi.org/10.1186/1471-2148-8-327" rev="review">10.1186/1471-2148-8-327</a></span>
<br />
<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Evolutionary+bioinformatics+online&rft_id=info%3Apmid%2F19204805&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Why+should+we+care+about+molecular+coevolution%3F&rft.issn=&rft.date=2008&rft.volume=4&rft.issue=&rft.spage=29&rft.epage=38&rft.artnum=&rft.au=Codo%C3%B1er+FM&rft.au=Fares+MA&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Codoñer FM, & Fares MA (2008). Why should we care about molecular coevolution? <span style="font-style: italic;">Evolutionary bioinformatics online, 4</span>, 29-38 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/19204805" rev="review">19204805</a></span>
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<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Journal+of+Biological+Chemistry&rft_id=info%3Adoi%2F10.1074%2Fjbc.M600349200&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Evolutionarily+Conserved+Allosteric+Network+in+the+Cys+Loop+Family+of+Ligand-gated+Ion+Channels+Revealed+by+Statistical+Covariance+Analyses&rft.issn=0021-9258&rft.date=2006&rft.volume=281&rft.issue=26&rft.spage=18184&rft.epage=18192&rft.artnum=http%3A%2F%2Fwww.jbc.org%2Fcgi%2Fdoi%2F10.1074%2Fjbc.M600349200&rft.au=Chen%2C+Y.&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Chen,
Y. (2006). Evolutionarily Conserved Allosteric Network in the Cys Loop
Family of Ligand-gated Ion Channels Revealed by Statistical Covariance
Analyses <span style="font-style: italic;">Journal of Biological Chemistry, 281</span> (26), 18184-18192 DOI: <a href="http://dx.doi.org/10.1074/jbc.M600349200" rev="review">10.1074/jbc.M600349200</a></span><br />
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<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Bioinformatics&rft_id=info%3Adoi%2F10.1093%2Fbioinformatics%2Fbtm604&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Mutual+information+without+the+influence+of+phylogeny+or+entropy+dramatically+improves+residue+contact+prediction&rft.issn=1367-4803&rft.date=2007&rft.volume=24&rft.issue=3&rft.spage=333&rft.epage=340&rft.artnum=http%3A%2F%2Fbioinformatics.oxfordjournals.org%2Fcgi%2Fdoi%2F10.1093%2Fbioinformatics%2Fbtm604&rft.au=Dunn%2C+S.&rft.au=Wahl%2C+L.&rft.au=Gloor%2C+G.&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Dunn,
S., Wahl, L., & Gloor, G. (2007). Mutual information without the
influence of phylogeny or entropy dramatically improves residue contact
prediction <span style="font-style: italic;">Bioinformatics, 24</span> (3), 333-340 DOI: <a href="http://dx.doi.org/10.1093/bioinformatics/btm604" rev="review">10.1093/bioinformatics/btm604</a></span>
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<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Molecular+Biology+and+Evolution&rft_id=info%3Adoi%2F10.1093%2Fmolbev%2Fmsq004&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Functionally+Compensating+Coevolving+Positions+Are+Neither+Homoplasic+Nor+Conserved+in+Clades&rft.issn=0737-4038&rft.date=2010&rft.volume=27&rft.issue=5&rft.spage=1181&rft.epage=1191&rft.artnum=http%3A%2F%2Fmbe.oxfordjournals.org%2Fcgi%2Fdoi%2F10.1093%2Fmolbev%2Fmsq004&rft.au=Gloor%2C+G.&rft.au=Tyagi%2C+G.&rft.au=Abrassart%2C+D.&rft.au=Kingston%2C+A.&rft.au=Fernandes%2C+A.&rft.au=Dunn%2C+S.&rft.au=Brandl%2C+C.&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Gloor, G., Tyagi, G., Abrassart, D., Kingston, A., Fernandes, A., Dunn, S., & Brandl, C. (2010). Functionally Compensating Coevolving Positions Are Neither Homoplasic Nor Conserved in Clades <span style="font-style: italic;">Molecular Biology and Evolution, 27</span> (5), 1181-1191 DOI: <a href="http://dx.doi.org/10.1093/molbev/msq004" rev="review">10.1093/molbev/msq004</a></span>
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<br /></div>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-51213063830506316802011-10-11T17:46:00.000+03:002011-10-11T17:46:28.654+03:00PVC bacteria and the prokaryote to eukaryote transition... maybe not.<div dir="ltr" style="text-align: left;" trbidi="on">
It was an interesting hypothesis, but it seems <a href="http://proteinevolution.fieldofscience.com/2011/01/kinky-evolution-did-we-evolve-from-pvc.html">the evidence for an origin of eukaryotes in the Planctomycetes, Verrucomicrobia, Chlamydiae (PVC) bacterial superphylum</a>, as proposed by <a href="http://www.sciencemag.org/content/330/6008/1187.full"> Devos and Reynaud in a </a><a href="http://www.sciencemag.org/content/330/6008/1187.full">Science article</a> doesn't hold up to scrutiny.<br />
<br />
In a <a href="http://www.ncbi.nlm.nih.gov/pubmed/21858844">recent paper by James McInerney <i>et al.</i> in Bioessays</a>, the authors address each of the claimed eukaryote-like features and show that they are all likely to be either analogous (the result of parallel evolution, not shared ancestry), or are the result of horizontal gene transfer (HGT) events. In the words of the authors:<br />
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<blockquote>
PVC are no more intermediates in the prokaryote-to-eukaryote transition than dragonflies are intermediates in the evolutionary sequence linking bony fish and birds.</blockquote>
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The Bioessays paper is an important reminder that for any grand hypotheses about evolution, distinguishing between homologous and analogous characters is critical, as is establishing the direction of inheritance. And by far the best way to address these points is by taking advantage of the mass of genomic data available.</div>
Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-46415619562782261242011-09-21T17:44:00.001+03:002011-09-23T21:29:07.067+03:00Molecular biology in the light of comparative genomics.<div dir="ltr" style="text-align: left;" trbidi="on">
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The week before last, I was at a conference at EMBL Heidelberg on Protein Synthesis and Translational control. I found it to be a stimulating, very enjoyable meeting, despite being rather disappointed by it being dominated by eukaryotic mechanisms, with only a few talks devoted to bacterial translation (and from what I remember none on organellar or archaeal translation). Translation is a universal, ancient process, and analyses of its highly conserved components have taught us much of what we know about the evolution and diversity of life on Earth. Despite that, out of ~300 (I would guess) participants, I was the only person presenting evolution stories. I wasn't selected for a talk, but I presented two posters, one on the RelA/SpoT family of ribosome-associated starvation response enzymes and one on gain and loss of mitochondrial translational initiation factors. I'm also pretty sure I was the only blogger and tweeter there too... hmm is that connected? Anyway, that's not the point here. My point is that a little evolution goes a long way in terms of predicting functions and universality of mechanisms, and it seems to me that molecular biologists aren't taking full advantage of that. There were a few talks mentioning new factors. My immediate thoughts were what are they related to? What do
sequence comparisons suggest about them? Are they actually in any other
organisms than yeast or humans? Model organisms are unfortunately not always representative, and we need evolutionary analyses to put results in perspective.</div>
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It's not just at this protein synthesis conference that I was the one and only molecular evolutionary biologist. Except for studies on ribosome origin, which are often low on evidence, high on speculation, and conducted by non-experts in molecular evolution (<a href="http://proteinevolution.fieldofscience.com/2011/04/ancestral-ribosome-my-reservations.html">see my previous blog post</a>), it's the same in the last few conferences I've been to. The protein synthesis field is a very active, exiting field with great people who are not afraid of bioinformatics and collaborating with bioinformaticians. Just, usually not molecular evolutionary biologists. That doesn't mean that people can't be enlightened though. After the first day, a co-attendee chatted with me about my research. He'd come across my paper of <a href="http://mbe.oxfordjournals.org/content/early/2010/11/22/molbev.msq316.abstract">EF-G duplication and functional evolution</a> and was excited by it. He said "I thought evolution was really boring, but actually it's interesting and very useful." He went on to propose an interesting collaborative project.</div>
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It's not that there are no published comparative genomics
studies done at all in the protein synthesis field, just there are very few and though some are good, more often they are done badly
(for example claiming orthology seemingly without making phylogenetic
trees and getting it wrong), and with the focus on distribution without site-specific or
structural analyses to make functional inferences. Specific expertise is required to do it right. The kind of expertise found in evolutionary biologists. However, the latter tend to stick to the evolution field, and it seems to me that important
questions don't always get answered that way. I'm not sure, but I would hazard a guess that it's the same in other molecular mechanism fields (eg transcription, cell cycle/replication). There are lots of gaps in our knowledge about core cellular processes
that need filling with the help of people competent in comparative genomics. </div>
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The scarcity of other molecular evolutionary biologists within the protein synthesis field could be considered to be an advantage for me. I have my own niche afterall, and I have no shortage of work because not all experimentalists overlook the importance of evolution. However, there are many, many more interesting proteins and and questions than I have time to look at. And I don't have a lab of minions as yet. </div>
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Here's an example of how wrong conclusions can be propagated in the absence of molecular evolution analyses. It is discussed in a paper that I'm writing up at the moment. I'll blog the full story with the real proteins named in the fullness of time, but this is just for the idea.</div>
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<a href="http://3.bp.blogspot.com/-bhgjBtlGo3I/TnnWF5yK_lI/AAAAAAAAAMc/R4hJnKjBXyg/s1600/rainbowtree_2.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="176" src="http://3.bp.blogspot.com/-bhgjBtlGo3I/TnnWF5yK_lI/AAAAAAAAAMc/R4hJnKjBXyg/s640/rainbowtree_2.png" width="640" /></a></div>
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So, in an original paper, it was claimed that an insertion in human mitochondrial protein 1 in figure A, above compensates for the function of protein 2, present and essential in <i>E. coli</i>, but lost in humans. The insertion is not at all homologous to protein 2. Nevertheless, if <i>E. coli</i> protein 1 is modified to include the insertion usually only found in humans, protein 2, which is usually essential, becomes dispensable. So the authors of the original study claimed that the insertion evolved in eukaryotes to replace the function of protein 2. This is all very interesting, but I immediately had a question. Since protein 2 is universally absent in eukaryotes (this is already known), is the insertion universally present in eukaryotes? I think this is a very important question, which was not addressed in the original paper. Nevertheless, there has been a whole slew of other papers propagating the conclusion that the insertion evolved to take the place of protein 2. </div>
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I was not content with an evolutionary conclusion drawn on the comparison of three organisms (the third was archaea, also missing the insertion), so I decided to answer this question myself. The result was oops. The insertion is actually only in vertebrates (see figure B, above). So for millions of years, eukaryotes had been (and many still are) doing fine without either the insertion or protein 2. Maybe the insertion does replace the function of protein 2 in vertebrates, but there must be some other, unknown, possibly more general mechanism(s) compensating. And this is an interesting avenue worth pursuing. </div>
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That's one angle to the story, and it's a bit negative, true, but there's also a very positive angle to this particular paper that I'm writing. There is a protein 3, also universal in bacteria, and almost universal in mitochondria. It had never previously been found in yeast, however with some sensitive sequence searching (PSI-blast) I found a homologue, which I confirmed as the orthologue with phylogenetic analysis. This yeast protein 3 is very divergent though, with insertions and deletions relative to the well known ones, so whether it is the functional equivalent of protein 3 was still unknown. But that's when it becomes wonderful to be an evolutionary biologist among experimentalists, because our collaborators have been able to confirm the function of my newly identified protein <i>in vivo</i>. So we have identified a new protein in yeast, essential for mitochondrial function, and a really nice evolutionary story to go along with it.</div>
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In conclusion, it's said so many times that it's becoming a nasty cliche, but Dobzansky's quote "nothing in biology makes sense except in the light of evolution" is spot on. I would encourage experimentalists to consider whether molecular evolution can help answer some of your questions, or even raise some exciting new ones. I would also urge molecular evolutionary biologists to consider collaborating with experimentalists whenever you can, because it's so exciting and satisfying to get your predictions tested.</div>
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OK, now to finish this paper about proteins 1, 2 and 3, which I will blog about when the paper is published and available!</div>
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Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com4tag:blogger.com,1999:blog-1554503874313461433.post-9786167308615390282011-08-14T20:39:00.000+03:002011-08-14T20:39:52.963+03:00Molecular evolution of RSH proteins, lookouts and messengers of stress signalsA few days ago (the day before my 30th birthday actually), my most recent paper, along with Vasili Hauryliuk and Tanel Tenson, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023479">"The RelA/SpoT Homolog (RSH) Superfamily: Distribution and Functional Evolution of ppGpp Synthetases and Hydrolases across the Tree of Life" was published with PloS ONE</a>. Hurrah!<br />
<br />
The RSH proteins comprise a superfamily of enzymes that synthesize and/or hydrolyze the alarmone ppGpp. ppGpp is a nucleotide that acts as an alarm signal, activating the “stringent” response in bacteria during starvation conditions and regulating various other aspects of cellular metabolism, often in response to stress. <a href="http://stringentresponse.blogspot.com/search/label/stringent%20response">Vasya's blog has a wealth of information about the stringent response and the molecules involved.</a><br />
<br />
Rel, RelA and SpoT are the classical, most well known “long” RSHs. The carry the ppGpp hydrolase, synthetase, TGS and ACT domain architecture. They have been found across diverse bacteria and plant chloroplasts. Additionally, dedicated single domain ppGpp-synthesizing and -hydrolyzing RSHs have also been discovered in disparate bacteria and animals respectively. However, until now there has been considerable confusion in terms of nomenclature, and no comprehensive phylogenetic and sequence analyses have previously been carried out to classify RSHs on a genomic scale.<br />
<br />
To remedy the situation, I carried out high-throughput sensitive sequence searching of over 1000 genomes from across the tree of life, in conjunction with phylogenetic analyses, to identify and classify diverse RSHs in different organisms and unify the terminology for the field. We classify RSHs into 30 subgroups comprising three groups: long RSHs, small alarmone synthetases (SASs), and small alarmone hydrolases (SAHs). That's 19 more subgroups than were previously known. Those previously unidentified RSH subgroups, which are mostly found in bacteria, but sometimes in archaea and eukaryotes, can now be studied experimentally.<br />
<br />
<div class="separator" style="clear: both; text-align: center;"><a href="http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0023479.g001&representation=PNG_L" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0023479.g001&representation=PNG_L" width="300" /></a></div><br />
What I think is possibly the most interesting result came from comparative sequence analysis of long and small RSHs. I found exposed sites limited in conservation to the long RSHs that seem to be involved in transmitting regulatory signals. These signals may be transmitted via inter-domain interactions, or inter-molecular interactions either among individual RSH molecules or among long RSHs and other binding partners such as the ribosome. These sites in RelA can now be directly targeted with mutagenesis in order to text these predictions.<br />
<br />
<div class="separator" style="clear: both; text-align: center;"><a href="http://1.bp.blogspot.com/-bxx2uk62YU4/TkgDs9-rYSI/AAAAAAAAAMA/yw3Nyd76THo/s1600/fetchObject.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="332" src="http://1.bp.blogspot.com/-bxx2uk62YU4/TkgDs9-rYSI/AAAAAAAAAMA/yw3Nyd76THo/s400/fetchObject.png" width="400" /></a></div><br />
I have to say I'm disappointed with how the figures look in the PDF version of the paper. Lines are really not as crisp as my uploaded figures. Unfortunately the tables also don't look how they're supposed to due to them having being automatically formatted for the PLoS format. I wasn't given the opportunity to check them in a proofing stage either. Oh well, I'm just happy this story is now out there!<br />
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<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=PLoS+ONE&rft_id=info%3A%2F&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=The+RelA%2FSpoT+Homolog+%28RSH%29+Superfamily%3A+Distribution+and+Functional+Evolution+of+ppGpp+Synthetases+and+Hydrolases+across+the+Tree+of+Life&rft.issn=&rft.date=2011&rft.volume=6&rft.issue=8&rft.spage=0&rft.epage=&rft.artnum=http%3A%2F%2Fwww.plosone.org%2Farticle%2Finfo%3Adoi%2F10.1371%2Fjournal.pone.0023479&rft.au=Gemma+C.+Atkinson&rft.au=Tanel+Tenson&rft.au=Vasili+Hauryliuk&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Gemma C. Atkinson, Tanel Tenson, & Vasili Hauryliuk (2011). The RelA/SpoT Homolog (RSH) Superfamily: Distribution and Functional Evolution of ppGpp Synthetases and Hydrolases across the Tree of Life <span style="font-style: italic;">PLoS ONE, 6</span> (8)</span>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0Tartu Parish, Estonia58.3708837 26.71482820000005658.3060877 26.469824700000057 58.4356797 26.959831700000056tag:blogger.com,1999:blog-1554503874313461433.post-20967386066859147262011-07-06T15:08:00.001+03:002011-07-06T15:10:34.427+03:00Drifting towards complexity, or complexity as a crutchFinally, I will finish this blog post, which I started months ago! I've been sooo busy with various things, including writing a paper (now in submission) and finishing off work for a handful of side projects, that my blog has become seriously neglected. However, now I have a (relatively) spare afternoon that I can devote to a bit of reading and blogging. <br />
<br />
The paper that I'm hastily refreshing my memory about is <a href="http://www.nature.com/nature/journal/v474/n7352/full/nature09992.html">"Non-adaptive origins of interactome complexity"</a>. However, I'm not going to blog too much about it, because <a href="http://skepticwonder.fieldofscience.com/2011/05/sticky-proteins-complexity-drama-and.html">PsiWaveFunction has written a very detailed piece</a>, that I highly recommend checking out. However, I'm very interested in this paper, so I can't resist blogging just a little bit about it! <br />
<br />
In the paper, Ariel Fernández and Michael Lynch consider the effect of population sizes on evolution of complexity, as measured by the number of protein-protein interactions. Multicellular eukaryotes have small popualtion sizes as compared to microbes, which leaves them vulnerable to the phenomenon of genetic drift, where changes get fixed in the population because they fail to get filtered out by efficient selection. These changes can sometimes be mildly deleterious. The type of deleterious mutations considered in this study are those that increase the area of the protein in contact with water (the protein-water interface or PWI), and so reduce the stability of the protein in solution.<br />
<br />
<br />
The authors find a correlation between drift and protein structural integrity, and suggest "that the emergence of unfavourable PWIs promotes the secondary recruitment of novel protein–protein associations that restore structural stability by reducing PWI". So essentially, proteins are recruited into multi-subunit complexes not to explore some new functional space as is commonly thought, but rather to stabilise decrepit proteins that have evolved through drift, itself caused by small population sizes.<br />
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<a href="http://proteinevolution.blogspot.com/2011/01/nature-of-our-last-common-ancestor.html">Like I've blogged about previously</a>, evolution does not always lead to the optimal solution. Just as long as a system is good enough to work, that's fine. And if that means employing some elaborate hacky, complex solution, that's not a problem (<a href="http://proteinevolution.blogspot.com/2011/01/nature-of-our-last-common-ancestor.html">just as long as you can handle a flabby genome</a>).<br />
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I like coming up with silly analogies, and in this case it's complexity as a crutch. Eukaryotic proteins are careless and clumsy, They end up lame, and although they can hobble around enough to get by, its easier with molecular crutches. But the big question is what is the order of events? Was the crutch being used before or after the protein became lame. <a href="http://onlinelibrary.wiley.com/doi/10.1002/iub.489/abstract">Lukeš et al</a>. argue that eukaryotic proteins were already messing about with crutches even before they needed them. This is so-called presupression or constructive neutral evolution (CNE).<br />
<br />
Presupression is a ratchet-like process, which <a href="http://onlinelibrary.wiley.com/doi/10.1002/iub.489/abstract">Lukeš et al</a> explain as follows:<br />
<br />
"A biochemical reaction under selection is catalyzed by a cellular component A (nucleic acid or protein) that fortuitously interacts with component B either directly, by binding, or indirectly, through the products of B’s own selected activity... The interaction, though not under selection, permits (suppresses) mutations in A that would otherwise inactivate it. Under these conditions, mutations will unavoidably occur, making A dependent on B."<br />
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But actually, both these models are not mutually exclusive. Whether in some cases complexity is a crutch that overcomes the limp of an already hobbling protein, or whether it is a fortuitous accessory which eventually becomes depended upon, we are beginning to understand that increasing complexity is probably largely a non-adaptive phenomenon, and not neccessarily the function builder that was previously thought.<br />
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<a href="http://skepticwonder.fieldofscience.com/2011/05/sticky-proteins-complexity-drama-and.html">And now I'll direct you over to the fabulous Sceptic Wonder blog by PsiWaveFunction, who's done an astounding job covering the Fernández and Lynch paper.</a><br />
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Also, watch this blog space for further discussion of the <a href="http://onlinelibrary.wiley.com/doi/10.1002/iub.489/abstract">Lukeš et al</a> paper, specifically their description of ribosome evolution under CNE. <br />
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<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Nature&rft_id=info%3Apmid%2F21593762&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Non-adaptive+origins+of+interactome+complexity.&rft.issn=0028-0836&rft.date=2011&rft.volume=474&rft.issue=7352&rft.spage=502&rft.epage=5&rft.artnum=&rft.au=Fern%C3%A1ndez+A&rft.au=Lynch+M&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Fernández A, & Lynch M (2011). Non-adaptive origins of interactome complexity. <span style="font-style: italic;">Nature, 474</span> (7352), 502-5 PMID: <a rev="review" href="http://www.ncbi.nlm.nih.gov/pubmed/21593762">21593762</a></span><br />
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<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=IUBMB+life&rft_id=info%3Apmid%2F21698757&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=How+a+neutral+evolutionary+ratchet+can+build+cellular+complexity.&rft.issn=1521-6543&rft.date=2011&rft.volume=63&rft.issue=7&rft.spage=528&rft.epage=37&rft.artnum=&rft.au=Luke%C5%A1+J&rft.au=Archibald+JM&rft.au=Keeling+PJ&rft.au=Doolittle+WF&rft.au=Gray+MW&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Lukeš J, Archibald JM, Keeling PJ, Doolittle WF, & Gray MW (2011). How a neutral evolutionary ratchet can build cellular complexity. <span style="font-style: italic;">IUBMB life, 63</span> (7), 528-37 PMID: <a rev="review" href="http://www.ncbi.nlm.nih.gov/pubmed/21698757">21698757</a></span>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-20344127873561095522011-05-17T10:52:00.000+03:002011-05-17T10:52:11.566+03:00Conference on antibiotics and protein synthesisNext month in Tartu there will be a<a href="conference:%20antibiotics%20inhibiting%20protein%20synthesis%20http://www.cecb.ut.ee/indexeng_files/conference.htm"> conference on antibiotics and protein synthesis </a>organized by <a href="https://www.etis.ee/portaal/isikuCV.aspx?PersonVID=36910">Tanel Tenson.</a><br />
<br />
Registration is FREE and now open!<br />
<br />
Confirmed speakers:<br />
<br />
James Williamson (Scripps Research Institute),<br />
Alexander Mankin (University of Illinois at Chicago),<br />
Steven Douthwaite (University of South Denmark),<br />
Daniel Wilson (University of Munich),<br />
Karen Shaw (Trius Therapeutics),<br />
Ada Yonath (Weizmann Institute of Science).<br />
Birte Vester (University of Southern Denmark)<br />
Joyce Sutcliffe (Tetraphase Pharmaceuticals)<br />
Mans Ehrenberg (Uppsala University)<br />
Chaitan Khosla (Stanford University)<br />
Markus Zeitlinger (Medical University of Vienna)<br />
<br />
It's also probable that <a href="http://stringentresponse.blogspot.com/">Vasili Hauryliuk</a> and I will be speaking too.Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-14761373859929592862011-05-11T17:56:00.003+03:002011-05-13T23:48:11.079+03:00the evolutionary rate of protein–protein interactionsThis is my first post for a while, since I've been pretty busy - first I was writing a grant proposal for some research money, then I was on holiday in Bavaria and Austria, after which I was busy finishing off a manuscript on evolution of starvation response enzymes. As of yesterday, the manuscript is with my boss, so time to catch up with the world.<br />
<br />
I noticed an interesting upcoming PNAS paper: <a href="http://www.pnas.org/content/early/2011/05/04/1104695108.abstract">Measuring the evolutionary rate of protein–protein interaction. This tackles a subject close to my heart - functional evolution of proteins.</a> The authors tackle measuring the rate at which functional changes happen, with function in this case measured by gain and loss of PPIs (protein-protein interactions).<br />
<br />
They start by comparing yeast <i>S. cerevisiae</i>, which has abundant PPI data with another yeast <i>Kluyveromyces waltii</i>. These two diverged ∼150 MYA, and they are sort of special relatives since a whole genome duplication occurred in the lineage to S. cerevisiae after the divergence of <i>K. waltii</i>. This worried me that this could affect the rate of PPI change, due to the sudden influx of homologues in the S. cerevisiae lineage inflating the PPI count. However, the problem of duplicates was surmounted by only considering one to one orthologs (ie proteins related by vertical descent and not gene duplication (which would be paralogues)). In all, 43 proteins passed the yeast 2 hybrid test for PPIs, and all of these were found to be conserved in both yeasts. From this, they estimated that the 95% confidence interval of the total rate of PPI evolution is between 0 and 4.6 × 10<sup>−10</sup> per PPI per year<br />
<br />
They then went on to consider animals. Using PPI data from nemtodes, they found two of five confirmed <i>S. cerevisiae</i> PPIs are conserved in <i>C. elegans</i>. These two species diverged ~1,300 MYA, so the 95% confidence interval is 1.6 × 10<sup>−10</sup> to 2.0 × 10<sup>−9</sup>. Using transcription factor PPI data from humans and mice, which diverged 90 MYA, they found that six of six mouse PPIs are conserved in humans. From this, they estimate the 95% confidence interval is 0 to 5.5 × 10<sup>−9</sup>. Using all the dataset together, they arrive at the final value for the rate of PPI change: (2.6 ± 1.6) × 10<sup>−10</sup> per PPI per year.<br />
<br />
It's great to have a value for the rate of this sort of rare evolutionary change, and the authors are certainly very rigorous is eliminating the possibility of false positives and false positives. However, I'm left wondering whether after all this filtering, they're left with enough data to be really sure of their estimates. I count 54 PPIs in total, of which only 3 are lost, and that's in one lineage. Is that really enough data to go on? Well, I'm certainly not a statistician, so I can only assume that this was checked out thoroughly by folks much more informed on this kind of thing than I am.<br />
<br />
An interesting future route would be to compare protein substitution and PPI rates between lineages. I'm wondering whether organisms with high amino acids substituion rates (like nematodes and other parasites) have a PPI rate that's (relatively) just as high, or whether this is dampened by compensatory mutations in binding interfaces. It'd also be interesting to compare the eukaryotic PPI rate to the bacterial one.<br />
<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft_id=info%3Apmid%2F21555556&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Measuring+the+evolutionary+rate+of+protein-protein+interaction.&rft.issn=0027-8424&rft.date=2011&rft.volume=&rft.issue=&rft.spage=&rft.epage=&rft.artnum=&rft.au=Qian+W&rft.au=He+X&rft.au=Chan+E&rft.au=Xu+H&rft.au=Zhang+J&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Qian W, He X, Chan E, Xu H, & Zhang J (2011). Measuring the evolutionary rate of protein-protein interaction. <span style="font-style: italic;">Proceedings of the National Academy of Sciences of the United States of America</span> PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/21555556" rev="review">21555556</a></span>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-50593755036517298752011-04-18T21:02:00.004+03:002011-04-18T21:07:59.258+03:00Detecting mutual exclusivity of gene familiesGene networks are popularly used in systems biology to show functional associations among genes within a single genome, taking advantage of available experimental data on intermolecular interactions. Co-evolutionary networks are another way of showing functional associations among genes, in this case using presence/absence patterns of homologous genes across genomes to predict likely interaction partners. A nice example from proteins that I'm interested in are the components of the selenocysteine incorporation machinery for incorporating the amino acid selenocysteine into growing peptides. Not all organisms utilise selenonocysteine, but those who do encode a whole package of genes for its synthesis, charging onto tRNA and delivery to the ribosome. If a gene X was to be found in only that strange collection of (not always closely related) organisms with the selenocysteine machinery, chances are that X either uses selenocysteine or is also involved in its metabolism. As an aside, <a href="http://string.embl.de/">STRING</a> is a really nice web application for visualising networks of functional associations compiled from various sources of evidence (co-occurence, co-expression, gene neighbourhood, and experiments). <br />
<br />
<a href="http://gbe.oxfordjournals.org/cgi/doi/10.1093/gbe/evr030">A new paper by Zhang et al. in GBE </a>presents a new and interesting approach for analysing co-evolutionary networks, by detecting Mutually Exclusive Orthologous Modules (MEOMs). In their words: "A MEOM is composed of two sets of gene families, each including gene families that tend to appear in the same organisms, such that the two sets tend to mutually exclude each other (if one set appears in a certain organism the second set does not)."<br />
<br />
MEOMs are interesting because they reflect the replacement of one set of genes by another. This could be due to lineage-specific or environment-specific adaptations. The authors analyze a co-evolutionary network based on 383 organisms from across the tree of life and find that MEOMs most often include gene families involved in transport, energy production, metabolism, and translation. They suggest that changes in the metabolic environment of an organism require adaptation to new sources of energy, and this triggers of replacement of genes, complexes and pathways in individual lineages. They also find many outer membrane proteins in their MEOMs, suggesting that as these proteins interact with the extracellular environment, they are frequently replaced during adaptation.<br />
<br />
It's all very interesting, and I hope the authors will consider making a searchable web interface to their database of MEOMs. Their supplementary data is a bit awkward to navigate, and this kind of data is just crying out for visualisation. I would love to be able to scan proteins in my data sets for potential MEOM membership. <br />
<br />
<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Genome+Biology+and+Evolution&rft_id=info%3A%2F10.1093%2Fgbe%2Fevr030&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Analysis+of+Co-evolving+Gene+Families+Using+Mutually+Exclusive+Orthologous+Modules&rft.issn=&rft.date=2011&rft.volume=&rft.issue=&rft.spage=&rft.epage=&rft.artnum=&rft.au=Xiuwei+Zhang&rft.au=Martin+Kupiec&rft.au=Uri+Gophna&rft.au=Tamir+Tuller&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Xiuwei Zhang, Martin Kupiec, Uri Gophna, & Tamir Tuller (2011). Analysis of Co-evolving Gene Families Using Mutually Exclusive Orthologous Modules <span style="font-style: italic;">Genome Biology and Evolution</span> : <a href="http://www.blogger.com/10.1093/gbe/evr030" rev="review">10.1093/gbe/evr030</a></span>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-24026045240342779192011-04-04T20:44:00.000+03:002011-04-04T20:44:36.649+03:00The ancestral ribosome: my reservations<div><style>
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</style> </div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;">I work on deep evolution of ribosome-associated proteins, so of course I'm very much excited by research on deep evolution of ribosomal RNA. However, I have some concerns about some of the work in this field relating to the composition and structure of the ancestral ribosome, or as sometimes called, proto-ribosome. Actually, it’s less that I have concerns about the work, more that I have some small, but (at least to me) important concerns about the interpretations and subsequent speculations. Anyway, the other day, as I listed to Ada Yonath's and Loren Williamson's talks at the <a href="http://suddath.gatech.edu/node/4">Suddath Symposium on the Ribosome</a>, I was reminded about these concerns, and decided it's probably a good idea to blog about them. </span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><br />
</div><div style="text-align: justify;"></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;">Before I start moaning, I want to stress that it's really exciting that people are trying to answer such deep evolutionary questions, and I genuinely think they have made some interesting and important discoveries about the relative ages of parts of the ribosome, and about small catalytic RNAs that can behave like ribosomes, I just don't think those catalytic RNAs <i>are</i> ancestral ribosomes. I think they are perhaps some shared component of ancestral and modern ribosomes</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><br />
</div><div style="text-align: justify;"></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;">What it comes down to is that in general the people working on proto-ribosomes are assuming that evolution proceeds from small and simple to large and complex. In fact, this is not necessarily the case, as <a href="http://proteinevolution.blogspot.com/2011/01/nature-of-our-last-common-ancestor.html">I have blogged about previously.</a> Small and perfectly formed is hard to evolve, while big and clumsy with time for optimisation is less hard.</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><br />
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</span></div><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="font-family: inherit; margin-left: 0px; margin-right: 0px; text-align: left;"><tbody>
<tr><td style="text-align: center;"><span style="font-size: small;"><a href="http://4.bp.blogspot.com/-nK8u1otKCaQ/TZeHmR5oZ-I/AAAAAAAAAJs/57DDUQtca0I/s1600/protorb.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="181" src="http://4.bp.blogspot.com/-nK8u1otKCaQ/TZeHmR5oZ-I/AAAAAAAAAJs/57DDUQtca0I/s400/protorb.jpg" width="400" /></a></span></td></tr>
<tr><td class="tr-caption" style="text-align: center;"><span style="font-size: x-small;">Figure 1. My crude drawing to demonstrate evolutionary progression. Green is the modern ribosome, with the predicted ancient parts in red. Black is sequence nonhomologous to the modern ribosome. A) shows the idea that is often presented: a small protoribosome gets bigger over time. B) shows my hypothesis: continual loss and gain of sequence with some retention of a conserved core.</span></td></tr>
</tbody></table><div style="font-family: inherit; text-align: justify;"><span style="font-size: small;">Ada Yonath’s talk at the symposium on the ancestral peptidyl transferase centre (PTC, the region where peptide bonds are formed between amino acids) really captured my imagination. The PTC is buried right in the middle of the ribosome and consists of two fragments of rRNA with rotational structural symmetry between the P (peptidyl) site tRNA binding rRNA and the A (acceptor) tRNA binding rRNA. This symmetrical region is highly conserved in sequence (98% identity among organisms), but not between each symmetrical unit. Ada proposes that this symmetrical region is the oldest part of the ribosome, and that this minimal region is a functional machine on its own. In support of this, the CCA-end of tRNA fits in perfectly, and their structural studies indicate it could provide a rotary motion of tRNAs that is required get peptidyl transfer. This is a really nice story, and so far I’m totally in support. What I have problems accepting is that this minimal rRNA dimer IS all that was present of the protoribosome (as in fig 1A). Why could there not have been extra RNA around it that was replaced during evolution (as in fig 1B)? Via the online participation (which was fantastic by the way) for the symposium I asked Ada about this:</span> </div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><br />
</div><div style="text-align: justify;"><blockquote style="font-family: inherit;"><div class="MsoNormal"><span style="font-size: small;">Gem: The small symmetrical region might be the only region modern ribosomes have in common with the ancestral proto-ribosome. But it almost seems TOO streamlined. Could the protoribosome actually have been bigger than that core region, and there could have been loss as well as gain of sequence? </span></div><div class="MsoNormal"><br />
</div><div class="MsoNormal"><span style="font-size: small;"></span></div><div class="MsoNormal"><span style="font-size: small;"></span></div><div class="MsoNormal"><span style="font-size: small;"></span></div><div class="MsoNormal"><span style="font-size: small;">Ada: we haven’t thought of that… but you can speculate anything.</span></div></blockquote><span style="font-size: small;"><span style="font-family: inherit;"> </span></span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><br />
</div><div style="text-align: justify;"><span style="font-size: small;"><span style="font-family: inherit;"> </span></span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;">That’s exactly my concern, that you can speculate anything in this field. There are very few clues to go on, and they don’t give anything conclusive. Where evidence dries up, all you can do are thought experiments, based on examples we know of. And we know from extant ribosomes that there have been lineage-specific loss and gain of sequence. Good examples are <a href="http://proteinevolution.blogspot.com/2011/02/rna-is-so-passe-mitochondrial-ribosomes.html">mitochondrial ribosomes which have lost a good deal of rRNA and replaced it with protein.</a></span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><br />
</div><div style="text-align: justify;"><span style="font-size: small;"><span style="font-family: inherit;"> </span></span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;">A similar model of ribosome evolution to Ada's, proposing progressive addition of rRNA onto a minimal but functional PTC frame is presented by Bokov and Steinberg, Nature (2009). In this paper, the authors examine the inter-domain interactions and structural dependencies in the large subunit to infer relative age. Again, this is great, fascinating work, and it is also consistent with a model of replacement and optimisation, rather that the “aggrandizement” that they presume in their model.</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><br />
</div><div style="text-align: justify;"><span style="font-size: small;"><span style="font-family: inherit;"> </span></span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;">After Ada Yonath’s talk in the symposium came Loren Williams, who also works on figuring out the ancestral ribosome. Williams and colleagues compared the sequences and structures of archaeon <i>H. marismortui</i> and bacterium <i>T. thermophilus</i> ribosomes and found that sequence and conformational similarity of the rRNAs are greatest near the PTC, and diverge smoothly with distance from it. They show a beautiful figure of the ribosome as an onion, which makes their point perfectly.</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><br />
</div><div style="text-align: justify;"><span style="font-size: small;"><span style="font-family: inherit;"> </span></span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;">Again, these particular results are very clear and interesting, it’s just some of the assumptions about the evolutionary process that I have issues with. I noticed in the talk that Loren consistently equated “conserved” with “old.” In fact, “conserved” usually means “important”. Jamie Williamson who was in the audience also made this point during the talk, and Loren replied that he could not argue with that. In the case of the ribosome, the central parts are not only involved in catalysis, they are also important for maintaining the three dimensional structure. So they are very important. It’s the same reason why proteins show strong conservation of buried amino acids.</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><br />
</div><div style="text-align: justify;"><span style="font-size: small;"><span style="font-family: inherit;"> </span></span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;">Some other evolutionary statements and suppositions by Loren also were a bit iffy, such as: "mitochondrial ribosomes are running evolution backwards." Yikes. Drastically cutting down rRNA and replacing with protein independently in multiple lineages is definitely not running evolution backwards… in fact evolution is never, ever backwards. I also have a problem with supposing things that it isn’t necessary to suppose: Loren hypothesises that the ribosome binding tails of ribosomal proteins are older than the globular domains, and were originally non-coded, they then became fused to globular domains. There really is no evidence for this as far as I can see. The tails and insertions that protrude into the ribosome are very biased in amino acid content, and if they’re anything like ribosome-binding extensions of translation factors such as IF3, they readily appear and vary in length and primary sequence during evolution. These sort of structures seem easy to add.</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><br />
</div><div style="text-align: justify;"><span style="font-size: small;"><span style="font-family: inherit;"> </span></span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;">Maybe my complaints can be considered to be petty in a field that is necessarily rife with speculations, but I just think it’s important not to push the speculations too far, in order to keep our scientific integrity and not become like the cranks that publish their “evolutionary biology” in the Journal of Cosmology. For example, I loved the first half of Ada’s talk, but she finished it with a discussion of the ability of her two symmetrical fragments to dimerise, and suggested that in a population of these fragments, their non-uniform tendency to dimerise was a kind of "pre darwinian Darwinian” ribosome evolution that took place in the prebiotic world. She also suggested that these fragments may also be proto-tRNAs. For me, this is too far removed from the evidence, and these are speculations too far.</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><br />
</div><div style="text-align: justify;"><span style="font-size: small;"><span style="font-family: inherit;"> </span></span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;">BUT! Having said all that, wild speculation is bloody well fun, so I will offer my own hypothesis (see fig. 1 B). I think the first ribosome could have been big, flabby and clumsy, an amalgamation of RNAs that were perhaps already involved in some other catalysis such as nucleic acid polymerisation, that through chance flopping around, managed to catalyse (probably in a very inefficient way) peptide bond formation. The efficiency of bond formation between particular amino acids may have been influenced by the certain nucleic acids being polymerised in the active site, as in some primitive ‘code’. This protein synthesising proto-machine maybe had nothing recognisably in common with modern ribosomes, but it was subsequently fine-tuned through loss of gain of sequence until it became something resembling the ribosome that we know and love. </span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;"><br />
</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;">Refs and further reading</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;"><br />
</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: small;"><br />
</span></div><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Biochemical+Society+transactions&rft_id=info%3Apmid%2F20298195&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Ancient+machinery+embedded+in+the+contemporary+ribosome.&rft.issn=0300-5127&rft.date=2010&rft.volume=38&rft.issue=2&rft.spage=422&rft.epage=7&rft.artnum=&rft.au=Belousoff+MJ&rft.au=Davidovich+C&rft.au=Zimmerman+E&rft.au=Caspi+Y&rft.au=Wekselman+I&rft.au=Rozenszajn+L&rft.au=Shapira+T&rft.au=Sade-Falk+O&rft.au=Taha+L&rft.au=Bashan+A&rft.au=Weiss+MS&rft.au=Yonath+A&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Belousoff MJ, Davidovich C, Zimmerman E, Caspi Y, Wekselman I, Rozenszajn L, Shapira T, Sade-Falk O, Taha L, Bashan A, Weiss MS, & Yonath A (2010). Ancient machinery embedded in the contemporary ribosome. <span style="font-style: italic;">Biochemical Society transactions, 38</span> (2), 422-7 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/20298195" rev="review">20298195</a></span><br />
<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Nature&rft_id=info%3Apmid%2F19225518&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=A+hierarchical+model+for+evolution+of+23S+ribosomal+RNA.&rft.issn=0028-0836&rft.date=2009&rft.volume=457&rft.issue=7232&rft.spage=977&rft.epage=80&rft.artnum=&rft.au=Bokov+K&rft.au=Steinberg+SV&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Bokov K, & Steinberg SV (2009). A hierarchical model for evolution of 23S ribosomal RNA. <span style="font-style: italic;">Nature, 457</span> (7232), 977-80 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/19225518" rev="review">19225518</a></span><br />
<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Molecular+biology+and+evolution&rft_id=info%3Apmid%2F19628620&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Peeling+the+onion%3A+ribosomes+are+ancient+molecular+fossils.&rft.issn=0737-4038&rft.date=2009&rft.volume=26&rft.issue=11&rft.spage=2415&rft.epage=25&rft.artnum=&rft.au=Hsiao+C&rft.au=Mohan+S&rft.au=Kalahar+BK&rft.au=Williams+LD&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Hsiao C, Mohan S, Kalahar BK, & Williams LD (2009). Peeling the onion: ribosomes are ancient molecular fossils. <span style="font-style: italic;">Molecular biology and evolution, 26</span> (11), 2415-25 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/19628620" rev="review">19628620</a></span>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com1tag:blogger.com,1999:blog-1554503874313461433.post-12434353240496841012011-03-18T15:10:00.006+02:002011-05-11T17:58:15.162+03:00Promiscuous proteins<div style="text-align: left;">Gone are the days when the one protein, one function presumption prevailed. Many proteins are multifunctional and multispecific, that is they have multiple binding partners for carrying out various roles in the cell. <a href="http://pubs.acs.org.ezproxy.its.uu.se/doi/abs/10.1021/bi101563v">Here's a new review by Erijiman et al. in Biochemistry</a> about multispecifity, covering various examples of promiscuous proteins and the different ways in which they achieve their multispecificity.<br />
<br />
Proteins can interact with multiple binding partners by having distinct binding interfaces or domains. By this route, it's possible for the protein to optimise each binding site for its specific partner as the interfaces are independent (although there may be some cross-talk). An example of this from the proteins that I'm interested in is the Rel protein of bacteria. This protein has a synthesis domain for producing the alarmone ppGpp, and a hydrolysis domain for degrading it. The interfaces are on different sides of the protein, so are in some sense independent, although binding of a molecule in one site may influence the function of the other site by <a href="http://www.cell.com/retrieve/pii/S0092867404002600">switching the conformation of the protein</a>.</div><div style="text-align: left;"><div style="text-align: left;"><br />
As an alternative solution, a protein may bind through one interface that is able to interact with multiple partners. An example of this is the archaeal elongation factor EF1A, which delivers <a href="http://www.pnas.org/content/early/2010/10/19/1009599107.abstract">aminoacylated tRNA, release factor aRF1 and mRNA decay protein aDom34</a> to the ribosome, binding all three by overlapping binding sites. </div><div style="text-align: left;"><br />
</div></div><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: 0px; margin-right: auto; text-align: left;"><tbody>
<tr><td style="text-align: center;"><a href="https://lh3.googleusercontent.com/-4VZ9_ZFURys/TYNTGtHVGFI/AAAAAAAAAJg/9KJhbnAds7U/s1600/bindinginterfaces.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="102" src="https://lh3.googleusercontent.com/-4VZ9_ZFURys/TYNTGtHVGFI/AAAAAAAAAJg/9KJhbnAds7U/s320/bindinginterfaces.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">My rather simplistic representation of how a protein's binding interfaces can be distributed. A: independent binding sites eg Rel. B: overlapping binding sites eg aEF1A. </td></tr>
</tbody></table><div style="text-align: left;"><br />
</div><div style="text-align: left;">Multispecificity is great for the cell (especially cells with reduced, streamlined genomes) in that from just one gene, you get a lot of functional value. However, it also introduces some compromises for the protein, in terms of optimising its specificity for binding partners (especially true for proteins with overlapping binding sites), and brings about challenges in terms of regulating the different functions. A way to escape these problems is by gene duplication and subfunctionalisation for the different binding functions of the protein. Indeed this has occurred in some organisms for both of my examples above. In proteobacteria, Rel has been duplicated, resulting in RelA and SpoT, specialised for ppGpp synthesis and hydrolysis respectively. Similarly, in eukaryotes, two duplications of EF1A-like proteins have led to eEF1A, eRF3 and Hbs1, specialised for binding aa-tRNA, eRF1 and eDom34 respectively. However, it would be wrong to say that eEF1A now only has one function, as in fact it has <a href="http://www.ncbi.nlm.nih.gov/pubmed/11866090">many many more functions</a>... but that's another story!</div><div style="text-align: left;"><br />
</div><div style="text-align: left;">For more info on these proteins, check out my other blog posts:</div><div style="text-align: left;"><a href="http://proteinevolution.blogspot.com/2011/03/just-how-hungry-am-i-and-what-would.html">- Just how hungry am I and what should I do about it (about RelA/Rel/SpoT) </a></div><div style="text-align: left;"><a href="http://proteinevolution.blogspot.com/2010/11/testing-predictions-from-phylogenetics.html">- Testing predictions from phylogenetics: mRNA decay mechanisms in archaea (about aEF1A) </a></div><div style="text-align: left;"><br />
</div><div style="text-align: left;"><br />
</div><div style="text-align: left;">Refs</div><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Biochemistry&rft_id=info%3Apmid%2F21229991&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Multispecific+recognition%3A+mechanism%2C+evolution%2C+and+design.&rft.issn=0006-2960&rft.date=2011&rft.volume=50&rft.issue=5&rft.spage=602&rft.epage=11&rft.artnum=&rft.au=Erijman+A&rft.au=Aizner+Y&rft.au=Shifman+JM&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Erijman A, Aizner Y, & Shifman JM (2011). Multispecific recognition: mechanism, evolution, and design. <span style="font-style: italic;">Biochemistry, 50</span> (5), 602-11 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/21229991" rev="review">21229991</a></span><br />
<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Cell&rft_id=info%3Apmid%2F15066282&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Conformational+antagonism+between+opposing+active+sites+in+a+bifunctional+RelA%2FSpoT+homolog+modulates+%28p%29ppGpp+metabolism+during+the+stringent+response+%5Bcorrected%5D.&rft.issn=0092-8674&rft.date=2004&rft.volume=117&rft.issue=1&rft.spage=57&rft.epage=68&rft.artnum=&rft.au=Hogg+T&rft.au=Mechold+U&rft.au=Malke+H&rft.au=Cashel+M&rft.au=Hilgenfeld+R&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Hogg T, Mechold U, Malke H, Cashel M, & Hilgenfeld R (2004). Conformational antagonism between opposing active sites in a bifunctional RelA/SpoT homolog modulates (p)ppGpp metabolism during the stringent response [corrected]. <span style="font-style: italic;">Cell, 117</span> (1), 57-68 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/15066282" rev="review">15066282</a></span><br />
<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft_id=info%3Apmid%2F20974926&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Omnipotent+role+of+archaeal+elongation+factor+1+alpha+%28EF1%CE%B1+in+translational+elongation+and+termination%2C+and+quality+control+of+protein+synthesis.&rft.issn=0027-8424&rft.date=2010&rft.volume=107&rft.issue=45&rft.spage=19242&rft.epage=7&rft.artnum=&rft.au=Saito+K&rft.au=Kobayashi+K&rft.au=Wada+M&rft.au=Kikuno+I&rft.au=Takusagawa+A&rft.au=Mochizuki+M&rft.au=Uchiumi+T&rft.au=Ishitani+R&rft.au=Nureki+O&rft.au=Ito+K&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Saito K, Kobayashi K, Wada M, Kikuno I, Takusagawa A, Mochizuki M, Uchiumi T, Ishitani R, Nureki O, & Ito K (2010). Omnipotent role of archaeal elongation factor 1 alpha (EF1α in translational elongation and termination, and quality control of protein synthesis. <span style="font-style: italic;">Proceedings of the National Academy of Sciences of the United States of America, 107</span> (45), 19242-7 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/20974926" rev="review">20974926</a></span>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-89207432795098279332011-03-12T13:12:00.002+02:002011-03-28T12:38:33.221+03:00Tsunami and earthquake crisis - Non-Believers Giving Aid<span class="Apple-style-span" style="border-collapse: separate; color: black; font-family: Verdana; font-size: small; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px;">Because praying for Japan doesn't help anyone, but donations save lives. </span><br />
<br />
<a href="http://givingaid.richarddawkins.net/"><span class="Apple-style-span" style="border-collapse: separate; color: black; font-family: Verdana; font-size: small; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px;"> http://givingaid.richarddawkins.net/</span></a><br />
<br />
<span class="Apple-style-span" style="border-collapse: separate; color: black; font-family: Verdana; font-size: small; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px;">"Non-Believers Giving Aid and the Richard Dawkins Foundation for Reason and Science are once more partnering with the<span class="Apple-converted-space"> </span><a href="http://www.icrc.org/" style="font-family: Verdana; margin: 0px; padding: 0px; position: relative; text-decoration: none;">International Committee of the Red Cross</a><span class="Apple-converted-space"> </span>to bring much needed help to people whose lives have been torn apart by natural disaster. Every cent and penny of money donated via Non-Believers Giving Aid will be forwarded to the International Red Cross – and if you are in the UK and you complete the Gift Aid Declaration along with your donation, we will pass that on in its entirety too."<span class="Apple-converted-space"> </span></span>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-84629492669519893422011-03-04T21:02:00.001+02:002011-03-04T21:05:37.499+02:00Well, this is unexpected! Drosophila mitochondrial translation elongation Factor G1 contains a nuclear localization signal.Most eukaryote genomes encode two mitochondrial translation elongation factor Gs. I recently had a <a href="http://mbe.oxfordjournals.org/content/28/3/1281.short">paper in MBE about the origin and evolution of these factors</a>, and <a href="http://proteinevolution.blogspot.com/2010/11/evolution-of-elongation-factor-g.html">I've blogged about it previously</a>. I spotted a very surprising article in PloS One today: <a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016799%20">"The Drosophila Mitochondrial Translation Elongation Factor G1 Contains a Nuclear Localization Signal and Inhibits Growth and DPP Signaling."</a> For some reason, mtEFG1 is dual targeted to the nucleus as well as the mitochondrion. The localisation signal is proposed to be found at the C terminus, unlike the mitochondrial transit peptide, which is found at the N terminus. The authors suggest a model in which "if mitochondrial ATP synthesis is low or EF-G1 is overexpressed and import of EF-G1 proteins into mitochondria is a limiting step, some EF-G1 proteins can accumulate outside of mitochondria and translocate into the nucleus, where they inhibit cellular growth and proliferation."<br />
<br />
The authors carry out mutagenesis and subcellular localization analysis of mtEFG1, and find that although the Drosophila mtEFG1 gene is essential, it's not required in every tissue. This leads them to suggest that in some tissues, mtEFG2 and not mtEFG1 is the primary translocation factor. This would be very unexpected as neither spirochete or <a href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WSR-4X3F7BR-D&_user=651519&_coverDate=08%2F28%2F2009&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_acct=C000035158&_version=1&_urlVersion=0&_userid=651519&md5=82e33a0dce44e867d7e34610b2798387&searchtype=a">human spd/mtEFG2 can not promote translocation, and instead spd/mtEFG2 is proposed to be specialised for EF-G's role in ribosome recycling.</a> Additionally, the alignment in my paper shows mtEFG2s don't have the conserved amino acids involved in translocation functions, such as interaction with peptidyl-tRNA. However intramolecular and ribosome interaction sites are well conserved in mtEFG2, suggesting it maintains EF-G-like structural integrity and ribosome binding abilities. Maybe this is sufficient to promote translocation in some conditions? In fact, even the more distantly related EF-G2 of Thermus, which belongs to a whole other ancient subfamily<a href="http://dx.doi.org/10.1016/j.molcel.2007.01.027"> is capable of translocation</a>, hinting that although classical EF-G is very well conserved at the primary sequence level, at least in some conditions the ribosome can accommodate and translocate with more divergent homologs that maintain an EF-G-like structure.<br />
<br />
The model of mtEFG1 subcellular location being related to mitochondrial ATP synthesis proposed by <span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=PloS+one&rft_id=info%3Apmid%2F21364917&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=The+Drosophila+Mitochondrial+Translation+Elongation+Factor+G1+Contains+a+Nuclear+Localization+Signal+and+Inhibits+Growth+and+DPP+Signaling.&rft.issn=&rft.date=2011&rft.volume=6&rft.issue=2&rft.spage=&rft.epage=&rft.artnum=&rft.au=Trivigno+C&rft.au=Haerry+TE&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Trivigno and Haerry presents a paradox, which they acknowledge: "If EF-G2 functioned as an elongation factors in tissues like the heart, mitochondrial translation and ATP synthesis would occur at normal levels, and EF-G1 would be imported into mitochondria and not accumulate in the nucleus. On the other hand, in tissues like the liver, where EF-G2 cannot function as an elongation factor, mitochondrial translation would decrease, ATP levels would drop, EF-G1 import into mitochondria would decrease and accumulation in the nucleus increase, which would further exacerbate the problem."</span><br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=PloS+one&rft_id=info%3Apmid%2F21364917&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=The+Drosophila+Mitochondrial+Translation+Elongation+Factor+G1+Contains+a+Nuclear+Localization+Signal+and+Inhibits+Growth+and+DPP+Signaling.&rft.issn=&rft.date=2011&rft.volume=6&rft.issue=2&rft.spage=&rft.epage=&rft.artnum=&rft.au=Trivigno+C&rft.au=Haerry+TE&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics"><br />
</span><br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=PloS+one&rft_id=info%3Apmid%2F21364917&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=The+Drosophila+Mitochondrial+Translation+Elongation+Factor+G1+Contains+a+Nuclear+Localization+Signal+and+Inhibits+Growth+and+DPP+Signaling.&rft.issn=&rft.date=2011&rft.volume=6&rft.issue=2&rft.spage=&rft.epage=&rft.artnum=&rft.au=Trivigno+C&rft.au=Haerry+TE&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">So, in conclusion, it's all rather surprising and the model just doesn't seem quite right... it's all very well for a bioinformatician to say this I know, but more experiments needed!</span><br />
<br />
Refs <br />
<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Molecular+biology+and+evolution&rft_id=info%3Apmid%2F21097998&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Evolution+of+elongation+factor+g+and+the+origins+of+mitochondrial+and+chloroplast+forms.&rft.issn=0737-4038&rft.date=2011&rft.volume=28&rft.issue=3&rft.spage=1281&rft.epage=92&rft.artnum=&rft.au=Atkinson+GC&rft.au=Baldauf+SL&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Atkinson GC, & Baldauf SL (2011). Evolution of elongation factor g and the origins of mitochondrial and chloroplast forms. <span style="font-style: italic;">Molecular biology and evolution, 28</span> (3), 1281-92 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/21097998" rev="review">21097998</a></span><br />
<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=PloS+one&rft_id=info%3Apmid%2F21364917&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=The+Drosophila+Mitochondrial+Translation+Elongation+Factor+G1+Contains+a+Nuclear+Localization+Signal+and+Inhibits+Growth+and+DPP+Signaling.&rft.issn=&rft.date=2011&rft.volume=6&rft.issue=2&rft.spage=&rft.epage=&rft.artnum=&rft.au=Trivigno+C&rft.au=Haerry+TE&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Trivigno C, & Haerry TE (2011). The Drosophila Mitochondrial Translation Elongation Factor G1 Contains a Nuclear Localization Signal and Inhibits Growth and DPP Signaling. <span style="font-style: italic;">PloS one, 6</span> (2) PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/21364917" rev="review">21364917</a></span><br />
<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Molecular+Cell&rft_id=info%3Adoi%2F10.1016%2Fj.molcel.2009.06.028&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=EF-G2mt+Is+an+Exclusive+Recycling+Factor+in+Mammalian+Mitochondrial+Protein+Synthesis&rft.issn=10972765&rft.date=2009&rft.volume=35&rft.issue=4&rft.spage=502&rft.epage=510&rft.artnum=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1097276509004663&rft.au=Tsuboi%2C+M.&rft.au=Morita%2C+H.&rft.au=Nozaki%2C+Y.&rft.au=Akama%2C+K.&rft.au=Ueda%2C+T.&rft.au=Ito%2C+K.&rft.au=Nierhaus%2C+K.&rft.au=Takeuchi%2C+N.&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Tsuboi, M., Morita, H., Nozaki, Y., Akama, K., Ueda, T., Ito, K., Nierhaus, K., & Takeuchi, N. (2009). EF-G2mt Is an Exclusive Recycling Factor in Mammalian Mitochondrial Protein Synthesis <span style="font-style: italic;">Molecular Cell, 35</span> (4), 502-510 DOI: <a href="http://dx.doi.org/10.1016/j.molcel.2009.06.028" rev="review">10.1016/j.molcel.2009.06.028</a></span><br />
<br />
<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Molecular+Cell&rft_id=info%3Adoi%2F10.1016%2Fj.molcel.2007.01.027&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Structural+Basis+for+Interaction+of+the+Ribosome+with+the+Switch+Regions+of+GTP-Bound+Elongation+Factors&rft.issn=10972765&rft.date=2007&rft.volume=25&rft.issue=5&rft.spage=751&rft.epage=764&rft.artnum=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1097276507000500&rft.au=Connell%2C+S.&rft.au=Takemoto%2C+C.&rft.au=Wilson%2C+D.&rft.au=Wang%2C+H.&rft.au=Murayama%2C+K.&rft.au=Terada%2C+T.&rft.au=Shirouzu%2C+M.&rft.au=Rost%2C+M.&rft.au=Sch%C3%BCler%2C+M.&rft.au=Giesebrecht%2C+J.&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Connell, S., Takemoto, C., Wilson, D., Wang, H., Murayama, K., Terada, T., Shirouzu, M., Rost, M., Schüler, M., & Giesebrecht, J. (2007). Structural Basis for Interaction of the Ribosome with the Switch Regions of GTP-Bound Elongation Factors <span style="font-style: italic;">Molecular Cell, 25</span> (5), 751-764 DOI: <a href="http://dx.doi.org/10.1016/j.molcel.2007.01.027" rev="review">10.1016/j.molcel.2007.01.027</a></span>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-51923876940504638112011-03-04T17:38:00.004+02:002011-03-04T19:11:30.891+02:00"Just how hungry am I? And what should I do about it?" How bacteria decide.<div style="font-family: inherit; text-align: left;"><i>Escherichia coli</i> bacteria may lack rumbling stomachs, but they know they're hungry when their ribosomes are empty. In starvation conditions, the lack of available amino acids leads to an increase in the cellular concentration of tRNAs that are uncharged with amino acids. The presence of uncharged tRNAs on the ribosome is sensed by the protein RelA in <i>E. coli </i>and other gamma- and beta-proteobacteria, and by close homologs called Rel or RSH in other bacteria. In such starved conditions, RelA-like proteins (from here-on I'll call them RSHs (RelA/SpoT Homologs) produce the small 'alarmone' molecule ppGpp. This onsets the so-called stringent response, where ppGpp induces changes in cell physiology, down-regulating the translation machinery and up-regulating amino acid biosynthesis machinery. It's also involved in responses to other environmental inputs such as glucose and fatty acid and iron availability. <a href="http://www.annualreviews.org/doi/abs/10.1146/annurev.micro.62.081307.162903">Here's a link to great review of ppGpp synthesis, hydrolysis and effects.</a></div><div class="separator" style="clear: both; font-family: inherit; text-align: left;"></div><div class="separator" style="clear: both; font-family: inherit; text-align: left;"></div><div class="separator" style="clear: both; font-family: inherit; text-align: left;"></div><div class="separator" style="clear: both; font-family: inherit; text-align: left;"></div><div style="font-family: inherit; text-align: left;"><div class="separator" style="clear: both; text-align: center;"><br />
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<div class="separator" style="clear: both; text-align: center;"><a href="https://lh5.googleusercontent.com/-00RhnzrjxLo/TXEJk1joRZI/AAAAAAAAAJc/u_tkzAgp0qA/s1600/piiic.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="195" src="https://lh5.googleusercontent.com/-00RhnzrjxLo/TXEJk1joRZI/AAAAAAAAAJc/u_tkzAgp0qA/s320/piiic.jpg" width="320" /></a></div><br />
</div><div style="font-family: inherit; text-align: left;">It's becoming clear that there is tight and complex regulation by ppGpp, and there are a couple of recent papers to this effect, which I'll briefly discuss. Using microarrays, <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2958.2010.07498.x/abstract">Traxler et al.</a> have carried out transcriptional profiling of the stringent response in <i>E. coli, </i>the organism where most research on bacterial stress and starvation has been carried out. They studied how ppGpp effects two transcriptional regulons, Lrp (<a href="http://www.ncbi.nlm.nih.gov/pubmed/12675791">leucine responsive protein</a> that regulates amino acid biosynthesis and transport) and the <a href="http://en.wikipedia.org/wiki/Sigma_factor">σ-factor</a> <a href="http://en.wikipedia.org/wiki/Sigma_38">RpoS</a> that regulates general stress response. They found that the Lrp regulon requires only a low level of ppGpp for its induction, while the RpoS regulon is induced only in high concentrations of ppGpp (also see <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2958.2010.07521.x/abstract">comment by Carlos Balsalobre</a>). Thus, the RpoS-dependent response is only triggered as a kind of emergency measure if the induction of the Lrp-dependent response has been induced and failed to save bacterial population growth.</div><div style="font-family: inherit; text-align: left;"><br />
</div><div style="font-family: inherit; text-align: left;">It is also becoming evident that the production of ppGpp and its effects differ among different bacteria. The bacterium <i>Caulobacter crescentus</i> lives in environments where amino acid concentrations are generally low. <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2958.2011.07602.x/abstract">Boutte and Crosson</a> have found that in this organism, ppGpp is synthesised in response to glucose and ammonium starvation, but not amino acid starvation. They find the RSH of this bacterium binds the ribosome, and exhibits "AND-type signaling logic", in which detection of an uncharged tRNA on the ribosome is a necessary but alone, insufficient signal for activation of ppGpp synthesis. This hints at synergistic control, where multiple starvation signals contribute to the accumulation of ppGpp at a high levels. This is different to the "OR-type" logic of <i>E. coli,</i> suggesting the environmental niche of the bug affects how starvation is perceived and dealt with.</div><div style="font-family: inherit; text-align: left;"><br />
The circuitry for ppGpp synthesis and its downstream effects are clearly intricate, involving feedback loops and inter-molecular cross-talk. I'm writing up some bioinformatic work now on the distribution and evolution of RSHs that synthesise or hydrolyse ppGpp, or do both. My results, like those of Boute and Crosson suggest the circuitry is dynamic across bacterial taxa, being often rewired during evolution with the help of gene duplications, domain gain and loss and horizontal gene transfer. This will be blogged of course!</div><div style="font-family: inherit;"><br />
</div><div style="font-family: inherit; text-align: left;">For more posts about the stringent response, <a href="http://stringentresponse.blogspot.com/">check out Vasya's blog</a><br />
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Refs</div><div style="font-family: inherit;"><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Molecular+microbiology&rft_id=info%3Apmid%2F21299642&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Discretely+calibrated+regulatory+loops+controlled+by+ppGpp+partition+gene+induction+across+the+%27feast+to+famine%27+gradient+in+Escherichia+coli.&rft.issn=0950-382X&rft.date=2011&rft.volume=79&rft.issue=4&rft.spage=830&rft.epage=45&rft.artnum=&rft.au=Traxler+MF&rft.au=Zacharia+VM&rft.au=Marquardt+S&rft.au=Summers+SM&rft.au=Nguyen+HT&rft.au=Stark+SE&rft.au=Conway+T&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Traxler MF, Zacharia VM, Marquardt S, Summers SM, Nguyen HT, Stark SE, & Conway T (2011). Discretely calibrated regulatory loops controlled by ppGpp partition gene induction across the 'feast to famine' gradient in Escherichia coli. <span style="font-style: italic;">Molecular microbiology, 79</span> (4), 830-45 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/21299642" rev="review">21299642</a></span></div><div style="font-family: inherit;"><br />
</div><div style="font-family: inherit;"><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Molecular+microbiology&rft_id=info%3Apmid%2F21299641&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Concentration+matters%21%21+ppGpp%2C+from+a+whispering+to+a+strident+alarmone.&rft.issn=0950-382X&rft.date=2011&rft.volume=79&rft.issue=4&rft.spage=827&rft.epage=9&rft.artnum=&rft.au=Balsalobre+C&rfe_dat=bpr3.included=1;bpr3.tags=Biology">Balsalobre C (2011). Concentration matters!! ppGpp, from a whispering to a strident alarmone. <span style="font-style: italic;">Molecular microbiology, 79</span> (4), 827-9 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/21299641" rev="review">21299641</a></span></div><div style="font-family: inherit;"><br />
</div><div style="font-family: inherit;"><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Molecular+microbiology&rft_id=info%3Apmid%2F21338423&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=The+complex+logic+of+stringent+response+regulation+in+Caulobacter+crescentus%3A+starvation+signaling+in+an+oligotrophic+environment.&rft.issn=0950-382X&rft.date=2011&rft.volume=&rft.issue=&rft.spage=&rft.epage=&rft.artnum=&rft.au=Boutte+CC&rft.au=Crosson+S&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Boutte CC, & Crosson S (2011). The complex logic of stringent response regulation in Caulobacter crescentus: starvation signaling in an oligotrophic environment. <span style="font-style: italic;">Molecular microbiology</span> PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/21338423" rev="review">21338423</a></span></div>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com2tag:blogger.com,1999:blog-1554503874313461433.post-78301007295012671292011-03-02T16:00:00.002+02:002011-03-04T19:13:26.793+02:00Pets in Tartu in need of good homesWe're traveling too much at the moment to get a pet, but we're looking forward to getting a cat as soon as we're settled enough. We're flying to Sweden tomorrow for a few weeks... and then, maybe when we're back in Tartu we could ask the landlady, just hypothetically of course, whether we'd be allowed to have a cat. I have a feeling she'll say yes, in which case, maaaybe we'll head over to the <a href="http://www.loomadevarjupaik.eu/">Tartu animal shelter</a> just to have a look... They have so many lovely animals there who are in need of good homes.<br />
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They list their cats online here:<br />
<a href="http://www.loomadevarjupaik.eu/kassid-koduootel/">http://www.loomadevarjupaik.eu/kassid-koduootel/</a><br />
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And dogs here:<br />
<a href="http://www.loomadevarjupaik.eu/koerad-koduootel/">http://www.loomadevarjupaik.eu/koerad-koduootel/</a><br />
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If you're in Tartu and are thinking about getting a pet, please consider the shelter first. It's run by volunteers who do a great job of caring for the animals, with very little money available to them.Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-49573634876832229542011-02-17T12:04:00.003+02:002011-03-02T16:32:51.850+02:00Guest post on the University of Tartu blogCommunicating research to a wide audience that includes non-scientists is a tough but fun challenge. I recently gave it a go in a guest post on the UT blog:<br />
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<a href="http://blog.ut.ee/in-the-light-of-evolution/">http://blog.ut.ee/in-the-light-of-evolution/</a>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com1tag:blogger.com,1999:blog-1554503874313461433.post-30715891005627813382011-02-17T11:58:00.000+02:002011-02-17T11:58:54.728+02:00Us humans are so generous with our genes, but how exactly?There's been a lot of chatter in the blogo/twittershere this morning about contamination of genomes, which is something I'm rather interested in, simply because I use genomes from all sorts of organisms all the time and <a href="http://proteinevolution.blogspot.com/2011/01/bacterial-contamination-in-eukaryotic.html">I've come across likely contaminants several times.</a><br />
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The sudden interest is down to two papers about human sequences in other genomes: <span style="font-size: small;">"Abundant Human DNA Contamination Identified in Non-Primate Genome Databases" by Longo <i>et al</i>. </span><a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016410">in PLoS ONE</a> and <span style="font-size: small;">"<span style="font-weight: normal;">Opportunity and Means: Horizontal Gene Transfer from the Human Host to a Bacterial Pathogen" by Anderson and Seifert </span></span><a href="http://mbio.asm.org/content/2/1/e00005-11.full">in MBio</a>.<br />
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<span style="font-size: small;">Longo <i>et al</i>. found primate-specific repetitive elements in the genomes of many different non-primates, which they put down to contamination from us DNA-shedding humans during sequencing. </span><span style="font-size: small;"><span style="font-weight: normal;">Anderson and Seifert on the other hand found another element in </span></span>human pathogen <em>Neisseria gonorrhoeae, </em><span style="font-size: small;"><span style="font-weight: normal;">which they instead put down to horizontal gene transfer.</span></span><em> </em><br />
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Can they both be right? On his blog, Mark Pallen suggests the <span style="font-size: small;"><span style="font-weight: normal;">Anderson and Seifert</span></span> results <i>might</i> also be contamination, <a href="http://pathogenomics.bham.ac.uk/blog/2011/02/human-dna-in-bacterial-genomes-yes-no-maybe/">but the debate is ongoing, so check his blog post for the full story.</a>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0tag:blogger.com,1999:blog-1554503874313461433.post-17733020951044000372011-02-11T11:22:00.004+02:002011-03-04T19:14:08.028+02:00Some good thoughts about Tartu, the city of good thoughtsSo far I haven't blogged about Tartu or Estonia, although I fully intended to when I started writing the blog. So OK, no time like the present.<br />
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="http://2.bp.blogspot.com/-N1R86i33DNU/TVTt-1ZRCcI/AAAAAAAAAIU/MkDAUpcsh2E/s1600/DSC00056.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="240" src="http://2.bp.blogspot.com/-N1R86i33DNU/TVTt-1ZRCcI/AAAAAAAAAIU/MkDAUpcsh2E/s320/DSC00056.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Tartu town square</td></tr>
</tbody></table>"City of good thoughts" is the official nickname of Tartu, and I guess it's supposed to conjure some impression of optimistic musings that might be inspired by the city, or maybe it's referring to the noble academic thoughts that are being spawned in the university. Maybe both. Anyway, Tartu has plenty of quirks, but on the whole I have good, positive thoughts about the place. So that's what this post will be about.<br />
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<tr><td style="text-align: center;"><a href="http://1.bp.blogspot.com/-inOjMfuTHSg/TVTt6eD6beI/AAAAAAAAAIA/vQlEaqgYdkQ/s1600/DSC00269.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="240" src="http://1.bp.blogspot.com/-inOjMfuTHSg/TVTt6eD6beI/AAAAAAAAAIA/vQlEaqgYdkQ/s320/DSC00269.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Tartu University main building. Lots of good thoughts going on inside, I'm sure. Though mostly administrative thoughts in this particular building. </td></tr>
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I moved from the UK in 2008 and spent two years working in Uppsala, Sweden. That happens to be where I am right now incidentally, since my partner Vasya has some work on at the uni here. Although it was a bumpy ride in Uppsala and I initially, unfairly blamed the country for that, over time I mentally separated the country from the stresses, and I grew to realise that I actually love Sweden, and would not mind ending up here. The country is beautiful, the quality of life is good and the language is learnable. I also have good friends here. So, I'd got used to Sweden, and I was a bit apprehensive about moving to Tartu to be honest... no mountains or coasts nearby, dreadful food (I'd visited Vasya several times and experienced some food horrors) and a frighteningly difficult language. I was expecting ex-soviet dreariness. But, after only 5 months living there, it really feels like home, unexpectedly so. And I wasn't hugely looking forward to leaving. <br />
<br />
What helps feeling settled of course is having a job you enjoy and being with your loved one in a cosy home. I have all of those, which are after all the main things that influence happiness in life (so I heard somewhere), and so I'm very content.<br />
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<tr><td style="text-align: center;"><a href="http://1.bp.blogspot.com/-XgSKUYP8Jfk/TVTuAlB9NmI/AAAAAAAAAIc/Dw2seVjSzoM/s1600/DSC00018.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="320" src="http://1.bp.blogspot.com/-XgSKUYP8Jfk/TVTuAlB9NmI/AAAAAAAAAIc/Dw2seVjSzoM/s320/DSC00018.jpg" width="240" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Our apartment in September (you can spot Vasya playing guitar on the balcony)...</td></tr>
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<tr><td style="text-align: center;"><a href="http://1.bp.blogspot.com/-MSrPXYXpj1k/TVTt9AWkSOI/AAAAAAAAAIM/b4Shjjm1Yqg/s1600/DSC00234.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" height="240" src="http://1.bp.blogspot.com/-MSrPXYXpj1k/TVTt9AWkSOI/AAAAAAAAAIM/b4Shjjm1Yqg/s320/DSC00234.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">...and just a couple of months later (too cold for outdoor serenades)</td></tr>
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<br />
But home life and work life aren't the only things about Tartu that I like. Here are a few other things:<br />
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1. It's just so different. It's really not like Britain, and though I'm proud to be British, I feel like I know my homeland pretty well, and it's an adventure trying on a strange country for size. And Estonia really can be very strange, and therefore funny. Maybe it's my taste in surreal humour... <br />
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<tr><td style="text-align: center;"><a href="http://3.bp.blogspot.com/--gk2hMEKyK4/TVTt47-l_FI/AAAAAAAAAH8/UONBlifqzHU/s1600/DSC00271.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="240" src="http://3.bp.blogspot.com/--gk2hMEKyK4/TVTt47-l_FI/AAAAAAAAAH8/UONBlifqzHU/s320/DSC00271.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">This slightly terrifying merry-go-round appears every christmas. That's my British mate Ady, riding the filter-feeder pig.</td></tr>
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<tr><td style="text-align: center;"><a href="http://2.bp.blogspot.com/-R5zm8e0e0vY/TVTt7aOXixI/AAAAAAAAAIE/2VloKTdMBFA/s1600/DSC00251.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="240" src="http://2.bp.blogspot.com/-R5zm8e0e0vY/TVTt7aOXixI/AAAAAAAAAIE/2VloKTdMBFA/s320/DSC00251.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Last christmas a miniature galleon also suddenly appeared in town.</td></tr>
</tbody></table><br />
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2. There are plenty of pubs. I'm a Brit. I just love pubs. I also appreciate that there is no state monopoly on alcohol and ridiculous alcohol buying hours like there are in Sweden.<br />
<br />
3. Eating out in good restaurants is affordable. OK, so the food is so-so at best in the majority of places, but other places are fab, particularly the French place 'Crepe', The Italian place 'La Dolce Vita' and... I've forgotten its name, but the Georgian place. The Indian place Asian Chef is supposed to be great too, but we haven't tried it yet. By the by, <a href="http://emajoefood.blogspot.com/">here's a link a great blog on Tartu restaurants</a>.<br />
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4. It's rustic. Most things are made from wood. Houses, utensils, stuff like that. I like that. Maybe because my dad is a retired woodwork teacher. Souvenirs are genuine handicrafts, wood and wool. We have an open fire at home, and we get trailer-loads of wood delivered that we stack in our wood shed. It's so far from the stark, institution-like apartment blocks of Sweden. Snuggling by the fire when it's snowing outside is heaven!<br />
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<tr><td style="text-align: center;"><a href="http://4.bp.blogspot.com/-d9C_yxcEoMI/TVTuCLtfBvI/AAAAAAAAAIg/T2fwO07qKIo/s1600/photo.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="248" src="http://4.bp.blogspot.com/-d9C_yxcEoMI/TVTuCLtfBvI/AAAAAAAAAIg/T2fwO07qKIo/s320/photo.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">The September arrival of our wood for the winter! We've had to get another load delivered since then. </td></tr>
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<tr><td style="text-align: center;"><a href="http://3.bp.blogspot.com/-icFJ0iXvZCA/TVTt8G5cbzI/AAAAAAAAAII/6gR6eMriA8Q/s1600/DSC00240.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="240" src="http://3.bp.blogspot.com/-icFJ0iXvZCA/TVTt8G5cbzI/AAAAAAAAAII/6gR6eMriA8Q/s320/DSC00240.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">A cute, rustic cobbled street</td></tr>
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<tr><td style="text-align: center;"><a href="http://4.bp.blogspot.com/-xR7-B8bvE1o/TVTt_7mFUbI/AAAAAAAAAIY/G5ibNP6cgzg/s1600/DSC00037.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="240" src="http://4.bp.blogspot.com/-xR7-B8bvE1o/TVTt_7mFUbI/AAAAAAAAAIY/G5ibNP6cgzg/s320/DSC00037.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Wooden houses come in large size too</td></tr>
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5. It's semi-Russian. Vasya is Russian by birth, Belorussian by passport, and so I'm curious about Eastern cultures. Again, very different to Britain.<br />
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6. The snowy winters. I love snow. Our Estonian friend Arvi is "sick of this white shit", but I can't get enough of it. Hmm maybe that will all change when we buy a car though... <br />
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<tr><td style="text-align: center;"><a href="http://4.bp.blogspot.com/-I5ecDebsqN0/TVT7wqJTQaI/AAAAAAAAAIk/rEYYArKdbw0/s1600/DSC00299.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="240" src="http://4.bp.blogspot.com/-I5ecDebsqN0/TVT7wqJTQaI/AAAAAAAAAIk/rEYYArKdbw0/s320/DSC00299.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">"Snoooooowwwww!"</td></tr>
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7. The people. We know some great people in Tartu, including Vasya's and my boss Tanel, who we call the Godfather. That's less in the scary mafia way, and more in the wish-granting fairy godmother kind of way.<br />
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So those are the main things! Oh also, there's the fact that Tallinn isn't too far away, and it's beautiful. <br />
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<tr><td style="text-align: center;"><a href="http://3.bp.blogspot.com/-MsxZLDwRPdo/TVTt3do5uTI/AAAAAAAAAH4/hfevpLD3OuQ/s1600/DSC00326.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="240" src="http://3.bp.blogspot.com/-MsxZLDwRPdo/TVTt3do5uTI/AAAAAAAAAH4/hfevpLD3OuQ/s320/DSC00326.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Tallinn at Christmas</td></tr>
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<tr><td style="text-align: center;"><a href="http://3.bp.blogspot.com/-AT4yYCURkJg/TVT8GVwgUlI/AAAAAAAAAIo/pKj7gb1xgy4/s1600/DSC00307.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="240" src="http://3.bp.blogspot.com/-AT4yYCURkJg/TVT8GVwgUlI/AAAAAAAAAIo/pKj7gb1xgy4/s320/DSC00307.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Tallin city walls</td></tr>
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So there you go!<br />
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<tr><td style="text-align: center;"><a href="http://www.visittartu.com/" style="margin-left: auto; margin-right: auto;"><img border="0" src="http://www.visittartu.com/vvfiles/c/c89afb5ad8b0fee0ee23c8f7c87d6c52.gif" style="margin-left: auto; margin-right: auto;" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Pic from <a href="http://www.visittartu.com/">www.visittartu.com</a></td></tr>
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<ul></ul>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com4tag:blogger.com,1999:blog-1554503874313461433.post-62872194862138258092011-02-06T17:31:00.000+02:002011-02-06T17:31:48.327+02:00RNA is so passé. Mitochondrial ribosomes ditch rRNA in favour of proteinMitochondria are the energy-producing organelles of eukaryotes that evolved from a endosymbiotic bacterial ancestor, probably before the divergence of all known eukaryotes. They retain a minimal genome, which in humans amounts to just 37 genes: 13 for components of respiratory complexes and 24 for translation (22 transfer (t) RNAs and 2 ribosomal (r) RNAs).<br />
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Translation is pretty bizarre in mitochondria, and very different among different eukaryotic lineages in terms of mRNA features and involvement of protein factors. Vasya has covered some peculiarities of mitochondrial information processing in his blog posts <a href="http://stringentresponse.blogspot.com/2011/01/mitochondrial-mrna-utrs-insanity-lunacy.html">here</a>, <a href="http://stringentresponse.blogspot.com/2011/01/viral-nature-of-mitochondrial-rna.html">here</a> and <a href="http://stringentresponse.blogspot.com/2011/01/mitochondrial-translation-complete-mess.html">here</a>. I want to touch upon another part of it: rRNA reduction and replacement with protein.<br />
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The mammalian mitochondrial ribosome is bigger than that of its bacterial counterpart, however it contains less RNA, with the remainder of its mass being made up of ribosomal proteins (RBPs) that are encoded in the nucleus and post-translationally targeted to mitochondria. The extra RBPs that have evolved to replace the RNA tend to have no recognisable homologues in prokaryotic or eukaryotic cytoplasmic proteomes, and are evolving faster than cytoplasmic RBPs (O'Brien, 2002). <br />
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Nematode ribosomes are even more striking in their rRNA loss, as you can see from the figure below, and are even more protein-rich (Watanabe, 2010; <span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Biochemistry&rft_id=info%3Apmid%2F15966747&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Isolation+and+physiochemical+properties+of+protein-rich+nematode+mitochondrial+ribosomes.&rft.issn=0006-2960&rft.date=2005&rft.volume=44&rft.issue=25&rft.spage=9232&rft.epage=7&rft.artnum=&rft.au=Zhao+F&rft.au=Ohtsuki+T&rft.au=Yamada+K&rft.au=Yoshinari+S&rft.au=Kita+K&rft.au=Watanabe+Y&rft.au=Watanabe+K&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Zhao <i>et al</i>., 2005).</span><br />
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<div class="separator" style="clear: both; text-align: center;"></div><table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="http://3.bp.blogspot.com/_g0_qp9N1G7I/TU6vaDXqL2I/AAAAAAAAAHk/1JhqYOQDpV4/s1600/Screen+shot+2011-02-06+at+15.24.15.png" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="155" src="http://3.bp.blogspot.com/_g0_qp9N1G7I/TU6vaDXqL2I/AAAAAAAAAHk/1JhqYOQDpV4/s400/Screen+shot+2011-02-06+at+15.24.15.png" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;"><a href="http://www.blogger.com/goog_1280761630">Figure and caption from </a><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Proceedings+of+the+Japan+Academy%2C+Series+B&rft_id=info%3Adoi%2F10.2183%2Fpjab.86.11&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Unique+features+of+animal+mitochondrial+translation+systems&rft.issn=0386-2208&rft.date=2010&rft.volume=86&rft.issue=1&rft.spage=11&rft.epage=39&rft.artnum=http%3A%2F%2Fjoi.jlc.jst.go.jp%2FJST.JSTAGE%2Fpjab%2F86.11%3Ffrom%3DCrossRef&rft.au=WATANABE%2C+K.&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics"><a href="http://dx.doi.org/10.2183/pjab.86.11">WATANABE, K. (2010):</a> </span>Three-dimensional models for large mt ribosomal RNA (gray) from mammalian (middle) and C. elegans (right) mitochondria, based on the crystal structure of a bacterial 50S subunit108) (left). The outline shows an edge line of the crystal structure of the 50S subunit from the crown view. Some functional rRNA domains are colored: red, P loop; blue, A loop; green, S/R loop; light blue, L2 binding helix (H66). The topological orientation of the ribosomal protein is based on the model for the mammalian mt ribosome.</td></tr>
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So why is this happening? Maybe this replacement of RNA with protein is a part of the ongoing transition from the RNA world into the protein world. But why is this replacement so pronounced in mitochondria? I wonder whether instead, it might be linked to RNA stability within the unique mitochondrial environment. Only very few mRNAs are present in mitochondria. For most of the proteins required there, the mRNA and proteins are made elsewhere in the cell and only then targeted to mitochondria. Perhaps mitochondrial chemistry isn't RNA-friendly, and it's beneficial for the cell to cut it down wherever possible and replace with more stable protein. I'm intrigued, but really not sure about this, and couldn't find any references to back up the idea, so I'd be grateful for any comments or links to references that any readers may have!<br />
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<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Gene&rft_id=info%3Apmid%2F11943462&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Evolution+of+a+protein-rich+mitochondrial+ribosome%3A+implications+for+human+genetic+disease.&rft.issn=0378-1119&rft.date=2002&rft.volume=286&rft.issue=1&rft.spage=73&rft.epage=9&rft.artnum=&rft.au=O%27Brien+TW&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">O'Brien TW (2002). Evolution of a protein-rich mitochondrial ribosome: implications for human genetic disease. <span style="font-style: italic;">Gene, 286</span> (1), 73-9 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/11943462" rev="review">11943462</a></span><br />
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<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Proceedings+of+the+Japan+Academy%2C+Series+B&rft_id=info%3Adoi%2F10.2183%2Fpjab.86.11&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Unique+features+of+animal+mitochondrial+translation+systems&rft.issn=0386-2208&rft.date=2010&rft.volume=86&rft.issue=1&rft.spage=11&rft.epage=39&rft.artnum=http%3A%2F%2Fjoi.jlc.jst.go.jp%2FJST.JSTAGE%2Fpjab%2F86.11%3Ffrom%3DCrossRef&rft.au=WATANABE%2C+K.&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">WATANABE, K. (2010). Unique features of animal mitochondrial translation systems <span style="font-style: italic;">Proceedings of the Japan Academy, Series B, 86</span> (1), 11-39 DOI: <a href="http://dx.doi.org/10.2183/pjab.86.11" rev="review">10.2183/pjab.86.11</a></span><br />
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<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Biochemistry&rft_id=info%3Apmid%2F15966747&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=Isolation+and+physiochemical+properties+of+protein-rich+nematode+mitochondrial+ribosomes.&rft.issn=0006-2960&rft.date=2005&rft.volume=44&rft.issue=25&rft.spage=9232&rft.epage=7&rft.artnum=&rft.au=Zhao+F&rft.au=Ohtsuki+T&rft.au=Yamada+K&rft.au=Yoshinari+S&rft.au=Kita+K&rft.au=Watanabe+Y&rft.au=Watanabe+K&rfe_dat=bpr3.included=1;bpr3.tags=Biology%2CEvolutionary+Biology%2C+Molecular+Biology%2C+Bioinformatics">Zhao F, Ohtsuki T, Yamada K, Yoshinari S, Kita K, Watanabe Y, & Watanabe K (2005). Isolation and physiochemical properties of protein-rich nematode mitochondrial ribosomes. <span style="font-style: italic;">Biochemistry, 44</span> (25), 9232-7 PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/15966747" rev="review">15966747</a></span>Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com3tag:blogger.com,1999:blog-1554503874313461433.post-57944662679623874612011-02-06T13:31:00.001+02:002011-02-06T18:42:23.815+02:00I love snowboardingVasya and I are back in Uppsala, Sweden for while, and Sweden in February means snowboarding! Here is me at <a href="http://www.rommealpin.se/">Romme Alpin</a> yesterday, boarding, falling and boarding again.<br />
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</div><iframe allowfullscreen='allowfullscreen' webkitallowfullscreen='webkitallowfullscreen' mozallowfullscreen='mozallowfullscreen' width='320' height='266' src='https://www.blogger.com/video.g?token=AD6v5dxTenG3w1nG3KSVE7EET8m8JS5mYd7Kh8GUpX2PJi5_OjtcpIpEyRyFEcVEqLyIR8GdQzO4vjjEW7Cl4j8hhw' class='b-hbp-video b-uploaded' frameborder='0'></iframe><br />
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It was so good to be in the fresh mountain air after a week of working at home, and it was beautiful weather. Simply a perfect day on the mountain! And next weekend, we'll go back to Romme for my other winter sport love: downhill skiing!Gemhttp://www.blogger.com/profile/12414925004285922048noreply@blogger.com0