Time to sequence the 'red and the dead'

New projects could tackle the genomics of species both critically endangered and already extinct.

Never mind the size, look at the genes. Credit: Hulton Archive/Getty Images

On the first weekend in April, a couple of dozen leading molecular biologists, conservationists and museum curators gathered at Pennsylvania State University in University Park to brainstorm about ways of harnessing the power of the latest molecular sequencing techniques to conservation goals.

"The cost of genome sequencing is falling at an extraordinary rate," says workshop co-organizer Stephan Schuster of Penn State University, who was a driving force behind the 2008 sequencing of a woolly-mammoth genome, the first complete genome of an extinct animal. "Now it is possible to entertain sequencing the genomes of other extinct and endangered species, and the benefits could be huge." Referring to the 'Red List' of highly endangered species drawn up by the International Union for Conservation of Nature (IUCN), Schuster suggests that researchers should plan for sequencing "the red and the dead: a suite of carefully chosen endangered and extinct species."

Devin Locke of Washington University's Genome Center in St Louis, Missouri, showed just how great the potential of the new technology is when he told the workshop that, by the end of the year, he and his colleagues expect to be producing data at more than 500 times the rate they were capable of in 2006, using a suite of Illumina GAII instruments. Although the Illumina platform is not very well suited to sequencing genomes from species that have not been sequenced before, another high-throughput platform — Roche's Titanium 454 — fits that trailblazing role quite nicely; the technology was used on the mammoth and on the Neanderthal genome that is expected to be published later this year.

Conservation biologists want to use this sequencing power to study the extinction process itself. The idea is to sequence samples from the same species spanning several hundred or even thousands of years, using material from existing zoological, botanical and palaeontological collections. This could give entirely new perspectives on the effects of climate change, disease, invasive species and genetic structure. In the case of mammoths, for example, there is the promise of sequencing ancient DNA from hundreds, if not thousands, of specimens spanning tens of thousands of years, a record that would take in responses to the climate of the last ice age and its ending.

“We're hoping to get a feel for what role pathogens might be playing in modern declines. ”

A recent study showed the promise of such techniques by identifying the likely cause of extinction of the Christmas Island rat (Rattus macleari) (K. B. Wyatt et al. PLoS ONE 3, e3602; 2008). DNA lab work has shown that museum specimens collected before the arrival of black rats on the island were all free of trypanosome parasites, but many of those collected afterwards were not. "By studying historic extinction events, we're hoping to get a feel for what role such pathogens might be playing in modern declines," says Alex Greenwood of Old Dominion University in Norfolk, Virginia, a co-author on the paper.

Molecular data could also act as an objective metric for endangerment, says Schuster. Once it becomes clearer what happens to genetic diversity as a species approaches extinction, he says, "you could then take these hard-core sequencing data to political decision-makers and say, 'this absolutely has to stop' ".

If the case of the Tasmanian devil is anything to go by, though, politicians may not yet be ready to listen to geneticists. Schuster and workshop co-organizer Webb Miller, also of Penn State University, teamed up with Vanessa Hayes of the Children's Cancer Institute Australia in Sydney in late 2007 to sequence the genome of the Tasmanian devil, a species on the verge of extinction due to a communicable cancer.

The ultimate goal of identifying the genetic basis for resistance to the cancer (which some animals seem to show) is still some way off, but the researchers have already identified 50 gene markers that allow them to describe the genetic make-up of individual devils. As yet, however, there is no sign that the Tasmanian authorities are prepared to incorporate the maintenance of the genetic diversity that these markers can measure into the conservation plan for the species.

An IUCN representative, who did not attend the workshop, was uncertain whether genomic data would be of widespread benefit for conservation. "The study of species' genomes could prove valuable, but probably only in a very limited number of cases," says Jean-Christophe Vié, deputy head of the IUCN species programme in Gland, Switzerland. "For example, if it could help us solve the amphi­bian extinction crisis by explaining what makes so many amphibians vulnerable to the chytrid fungus, that would be a major contribution."

Curators at the meeting broadly welcomed the "red and dead" idea. "I don't think there will be any difficulty convincing museum people of having their specimens used for this work," says Richard Sabin, curator of mammals at the Natural History Museum in London.

But he points out that extracting DNA requires removing a sliver of tissue from the relevant museum specimen — not something curators take lightly — and the record for samples taken for genetic analysis is not good. Between 2000 and 2007, for example, Sabin says his museum granted 70 requests to sample mammal specimens, resulting in 674 tissue samples being taken. Only two gene sequences from all of these samples made it into the public gene database, GenBank. The reasons for such a low hit rate remain unclear, although failure to extract DNA might be one. But "it is critical for them to report back to us, even if they get nothing from a sample", says Sabin, who has toughened up the museum's policy to make sure this happens.

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IUCN red list

Mammoth genome project

Natural History Museum

Save the Tasmanian Devil

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Nicholls, H. Time to sequence the 'red and the dead'. Nature (2009). https://doi.org/10.1038/458812a

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