{"id":1902,"date":"2007-03-13T00:00:00","date_gmt":"2007-03-13T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/darwins-famous-finches-and-venters-marine-microbes\/"},"modified":"2007-03-13T00:00:00","modified_gmt":"2007-03-13T07:00:00","slug":"darwins-famous-finches-and-venters-marine-microbes","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/darwins-famous-finches-and-venters-marine-microbes\/","title":{"rendered":"Darwin&#8217;s famous finches and Venter&#8217;s marine  microbes"},"content":{"rendered":"<p>La Jolla, CA \u2013 Although the Gal\u00e1pagos finches were to play a pivotal role  in the inception of Darwin&#8217;s  theory of evolution through natural selection, he had no inkling of their  significance when he collected them during his voyage on the <em>HMS Beagle. <\/em><\/p>\n<p>Similarly, it is hard to predict the impact the vast amount  of marine microbial DNA  \u2013  collected during the <em>Sorcerer II<\/em> Global Ocean Sampling Expedition by J. Craig Venter,  Ph.D., and his team  \u2013  will have on our understanding of the natural world. <\/p>\n<p>&#8220;If anything, this is just the beginning,&#8221; says <a href=\"\/es\/faculty\/manning.html\/\">Gerard  Manning, Ph.D.<\/a>, director of the Razavi   Newman Center  for Bioinformatics at the Salk Institute for Biological Studies. &#8220;We&#8217;re  starting to explore this trove of sequences now, but it may be decades before  we fully understand it all.&#8221;<\/p>\n<p>Just like the famous ornithologist John Gould who had to  classify the Gal\u00e1pagos finches before they led Darwin on the right track, Manning and many  others have been busy during the last couple of months wading through roughly  7.7 million sequenced snippets of sea-borne genomic DNA to impose order on the  flood of data and to classify the identified proteins. <\/p>\n<p>Their findings are detailed in series of papers, published  in this week&#8217;s online edition of the journal <em>Public Library of Science Biology (www.plos.org).<\/em> <\/p>\n<p>The authors are plying the rapidly emerging trade of  metagenomics (also known as environmental genomics) that seeks to examine  genomic snapshots taken directly from the environment. <\/p>\n<p>&#8220;Metagenomics allows us to sample the 99 percent of all  bacteria that won&#8217;t grow in the lab,&#8221; explains Manning. &#8220;GOS opens a huge  window into biological and genomic diversity and, within this diversity, to  better understand many of the fundamentals of biology.&#8221; he adds.<\/p>\n<h3>Expanding the  universe of protein families<\/h3>\n<p>But instead of whole genomes, metagenomics produces a whole  grab bag of bits and pieces for which scientists have to develop new methods to  extract meaning. In one of the papers, an array of scientists, spearheaded by  first author Shibu Yooseph, Ph.D., and his colleagues at the Craig Venter  Institute, compared every DNA fragment with every other available DNA fragment  to produce clusters of related sequences. This exhaustive analysis predicted  more than 6 million proteins in the GOS data  \u2013  nearly twice the number of all  proteins ever described before  \u2013  and laid the groundwork for further studies.<\/p>\n<p>Manning, a co-author on Yooseph&#8217;s paper, looked at the other  side of the coin. He ran all the public sequences and GOS data against Pfam, a  collection of signature profiles for all known protein families. Each of these  profiles is an average of all known members of a certain protein family.<\/p>\n<p>&#8220;Instead of starting with a human kinase to find a bacterial  kinase, for example, you start with all of them together, which makes the  search much more sensitive, but also very computationally expensive,&#8221; Manning  says. &#8220;We did almost 350 million comparisons, which is probably an order of  magnitude or two more than anybody has ever done before.&#8221;<\/p>\n<p>Manning and co-author Yufeng Zhai, Ph.D., a bioinformatics  programmer in the Razavi Newman Center  for Bioinformatics at the Salk, could only accomplish this rather gargantuan  task with the help of Time Logic, a company in Carlsbad, California.  The company specializes in hardware that accelerates genomic searches. &#8220;We only  have one of their accelerators, but Time Logic stepped up and lent us eight  more,&#8221; says Manning. The final computation took two weeks, but would have taken  well over a century on a traditional computer. <\/p>\n<p>The Salk scientists could assign over half of all GOS  sequences to known protein families, and discovered that certain protein  profiles are more popular in the ocean or on land. For example, gram-positive  bacteria are best known for their hardy spores, but this ability has been  entirely lost in their marine relatives.. Flagella, whip-like extensions  propelling bacteria forward and pili, short extensions used to exchange genetic  material between bacteria (also known as microbial sex), are also less frequent  in marine environments. <\/p>\n<p>&#8220;By comparing our findings with the Yooseph clusters, we  also discovered hundreds of new gene families that hadn&#8217;t even been seen  before,&#8221; says Zhai and adds that by adding the diverse GOS data to known  profiles, &#8220;we were able to make them more sensitive and diverse, and so  increase their power to categorize novel sequences.&#8221;<\/p>\n<h3>Diversity of  microbial kinases<\/h3>\n<p>In a separate study, Manning, Zhai, and first author  Natarajan Kannan, Ph.D., a postdoctoral researcher in the lab of HHMI  investigator and UCSD professor Susan S. Taylor, Ph.D., traded the breadth of  the ocean survey for the depth of a single protein domain. They zoomed in on  kinases, extremely well studied enzymes, which control every aspect of  eukaryotic cell biology and are important cancer drug targets. They control the  activity of proteins and small molecules by attaching tiny phosphate groups to  them. By contrast, much less has been known about their bacterial counterparts.<\/p>\n<p>Again and again, the researchers combed the GOS data for  bacterial kinases, each time rebuilding their domain profiles by including the  new members found in the previous round. All in all, they dug up 45,000 protein  kinase sequences that fell into 20 distinct families, of which the eukaryotic protein kinases are just one. The additional 19  families spanned a huge range and included several that had never been  described before. <\/p>\n<p>&#8220;Prokaryotic protein-like kinases were considered to be some  sort of niche players, but actually they are more prevalent and widespread than  histidine kinases,&#8221; explains Manning. Bacteria were thought to rely mostly on  histidine kinases, which are structurally different from protein kinases, for  all their signaling needs.<\/p>\n<p>Even though the different kinase families had very little  similarity in their sequence, it emerged that 10 key residues were conserved in  almost all kinase families, fingering them as being at the core of what it  means to be a kinase. Seven of those had been previously known to be important  in human kinases, but the other three were unexpected finds. <\/p>\n<p>The other surprising finding was just how innovative and  plastic the different families were, even with these core residues, as one or  another family had found ways to eliminate any but one of the 10 key residues.  Using structural modeling, and patterns of sequence conservation, Kannan was  able to show that loss of one key residue could be compensated by changes  around other conserved regions of the protein, and that some of these changes  in bacterial kinases are also seen in specific human kinases.<\/p>\n<p>Says Manning, &#8220;By looking at all these very distant  microbial relatives we can understand more even about human kinases and their  relationship to cancer and other diseases. We go out into the ocean, we find  all this diversity and analyzing what&#8217;s new and what&#8217;s not new reflects back on  the things we thought we knew well.&#8221;<\/p>\n<p>Research done at the Salk Institute was supported by the  Razavi-Newman Foundation. <\/p>\n<h3>Sorcerer II Global  Ocean Sampling Expedition<\/h3>\n<p>The circumnavigating <em>Sorcerer  II<\/em> Expedition, named after the sailboat J. Craig Venter transformed into a  marine research vessel, was inspired in part by the journeys of the HMS Beagle  and the HMS Challenger in the nineteenth century. But unlike those pioneering  expeditions, the <em>Sorcerer II<\/em> team led  by J. Craig Venter and a globe-spanning network of collaborators are after tiny  microbes, classifying the species they encounter not by their appearance but by  their unique genetic code. <\/p>\n<p>The current studies analyze samples collected from surface  waters during the first phase (or first third) of the voyage, which led the <em>Sorcerer II<\/em> from Newfoundland through  the Panama Canal and Galapagos Island on to French Polynesia. Venter&#8217;s crew  siphoned seawater through a series of increasingly fine filters to collect the  microbes, which they sent back to the J. Craig Venter Institute in Maryland. <\/p>\n<p>In the lab, the scientists shredded the collected genetic  material in millions of random snippets and then determined their sequence.  Based on overlapping sequences, computer programs can then assemble longer  stretches and merge them into longer pieces of a genome. These so-called  &#8220;scaffolds&#8221; are a treasure trove for a diverse group of scientists, who try to  squeeze as much information as possible from the largest metagenomic dataset  ever collected. For more information about the expedition, please go to: the J.  Craig Venter Institute (URL: <a href=\"http:\/\/www.sorcerer2expedition.org\" target=\"_blank\">www.sorcerer2expedition.org<\/a> y <a href=\"http:\/\/www.venterinstitute.org\" target=\"_blank\">www.venterinstitute.org<\/a>)<\/p>\n<h3>About the Salk  Institute:<\/h3>\n<p>The Salk Institute for Biological Studies in La Jolla, California,  is an independent nonprofit organization dedicated to fundamental discoveries  in the life sciences, the improvement of human health, and the training of  future generations of researchers. Jonas Salk, M.D., whose polio vaccine all  but eradicated the crippling disease poliomyelitis in 1955, opened the  Institute in 1965 with a gift of land from the City of San Diego and the financial support of the  March of Dimes.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[],"disease-research":[],"class_list":["post-1902","disclosure","type-disclosure","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Darwin&#039;s famous finches and Venter&#039;s marine microbes - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/es\/news-release\/darwins-famous-finches-and-venters-marine-microbes\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Darwin&#039;s famous finches and Venter&#039;s marine microbes - 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