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‘Genome 10K’ To Sequence DNA Of 10,000 Vertebrates

Posted on: Wednesday, 4 November 2009, 16:00 CST

An international consortium of scientists is proposing to generate whole genome sequences for 10,000 vertebrate species using technology so new it hasn't yet been invented.

Known as the Genome 10K Project, the new plan is the most comprehensive study of animal evolution ever attempted.

Launched in April 2009 during a three-day meeting at the University of California, Santa Cruz, the Genome 10K project now involves more than 68 scientists, who refer to themselves as the Genome 10K Community of Scientists (G10KCOS). 

The scientists seek to assemble a genomic zoo --a collection of DNA sequences for 10,000 vertebrate species, approximately one for every vertebrate genus.

While the technology to complete the ambitious project is not yet available, the scientists say the new genome sequencing protocols may be available within a year or two.

The plan involves gathering specimens of thousands of animals from zoos, museums, and university collections throughout the world, and then sequencing the genome of each species to reveal its complete genetic heritage.

The project was conceived by David Haussler, professor of biomolecular engineering at UC Santa Cruz, Stephen J. O'Brien, chief of the Laboratory of Genomic Diversity at the National Cancer Institute, and Oliver A. Ryder, director of genetics at the San Diego Zoo's Institute for Conservation Research and adjunct professor of biology at UC San Diego.

"For the first time, we have a chance to really see evolution in action, caught in the act of changing whole genomes," said Haussler.

"This is possible because the technology to sequence DNA is thousands of times more powerful now than it was just a decade ago, and is poised to get even more powerful very soon."

The cost of genome sequencing has been declining steadily over the past several years, making the sequencing of 10,000 genomes a realistic possibility, O’Brien said.

"The original cost of sequencing the human genome by a major international consortium was over a billion dollars.”

"With the latest sequencing technology, it now costs $50,000 to $100,000 per genome. The price only needs to drop down another log or so to make the sequencing of 10,000 genomes possible."

Renowned geneticist and Nobel Laureate Sydney Brenner will also be participating in the project. 

"The most challenging intellectual problem in biology for this century will be the reconstruction of our biological past so we can understand how complex organisms such as ourselves evolved," he said.

"Genomes contain information from the past--they are molecular fossils--and having sequences from vertebrates will be an essential source of rich information."

During the UCSC meeting, 55 top scientists representing research centers, universities, major zoos and museums throughout the world worked through the challenging logistics involved in conducting such a bold project.

"These are scientists who have devoted their lives to biology, evolution, and the preservation of animals, and now they see an opportunity for deeper study," Haussler said.

"We came away from that meeting with a plan for moving forward and an extraordinary online database of samples from more than 16,000 different species of vertebrate animals compiled from more than 50 institutions."

After recruiting a few more critical scientists to broaden the depth of the collection, the scientists collaborated on the database (available at http://sampledb.genome10k.org/) and drafted a proposal.

Part of the initiative calls for the genomic database to be analyzed to reveal the evolutionary changes it records.  This will be annotated with experimental findings related to specific sites of change.

"Analysis of these data will be a far greater challenge than anything yet attempted in comparative genomics," Haussler said.

O'Brien said the team hopes the project will integrate genomic inference into nearly every aspect of vertebrate biological enquiry.

"Biological science is about understanding how species work, so having the genomes available for 10,000 species will give us a new sense to understand biology," he said.

"The genome is like a sixth sense, adding to what we can see, smell, taste, hear, and feel. If we have this information for species that are not generally studied, it will be a particularly strong arrow in the quiver of students of biology."

The scientists have identified specimens that span a wide range of evolutionary diversity, including living mammals, birds, reptiles, amphibians, and fishes.  Many of these species are threatened or endangered, O'Brien said.

"We are capturing what evolution left us with before the human population started impacting species--a set of genomes inclusive of the biota that a magnificent evolutionary process has produced.”

The scientists expect their project will provide a strong foundation for understanding the genetic basis of recent and rapid adaptive changes within vertebrate species and between closely related species.

The work could also help conservation efforts by enabling scientists to predict how species will respond to events such as climate change, pollution, diseases and invasive competitors.

"The risk of extinction is lessened for species for which we have a genome sequence, because it enables studies that can provide important information relevant to conservation," said Ryder.

Genome sequences will be particularly useful in efforts to assess genetic diversity among endangered populations.

"Any tool used so far for evaluating genetic diversity and genetic variation is overshadowed by the resolving power of genomic information," Ryder said.

The consortium reached a consensus on guidelines for the collection of samples, including the types and volumes of tissues, recommendations for preservation and documentation, and adherence to national and international statutes regulating the collection, use, and transport of biological specimens.

Where possible, specimens for each species include both males and females and reflect geographic diversity or diversity within localized populations.

When completed, the collection will include more than a thousand frozen samples of fibroblast cells derived from 602 different vertebrate species.  These samples, maintained by the San Diego Zoo, the National Cancer Institute, and the world's cell repositories, are an important resource for genetic studies, said Ryder.

"When you sequence a whole genome, it may be 3 billion bases, of which only a few percent code for genes. If you want to quickly learn something about the genes, you can sequence the RNA transcripts of the genes. These cells are robust sources of high-quality RNA," he said.

The evolution of species living today involved ancient genetic changes still preserved in their DNA.  The Genome 10K project can help reveal answers to longstanding questions about the history of evolution.

Having full genomes available will enable detailed studies of base-by-base evolutionary changes throughout the genome.

"Differences in the DNA that makes up the genomes of the animals we find today hold the key to the great biological events of the past, such as the development of the four-chambered heart and the magnificent architecture of wings, fins and arms, each adapted to its special purpose," said Haussler.

O’Brien said the most challenging aspects of the project are now set to begin.

"The first challenge is to bring this whole promise into reality by actually getting samples, characterizing them, doing quality control on them, and delivering them to sequencing centers that can accomplish the goal," he said.

"The second is to very quickly raise the money to pay for sequencing and analysis and annotation of the sequences."

Haussler, O’Brien and Ryder outlined the consortium’s proposal to create a collection of tissue and DNA specimens for the project in a paper to be published online November 5 in the Journal of Heredity.

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Source: RedOrbit Staff & Wire Reports

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