Researcher rues loss as marsupial genome opportunities hop overseas

By Graeme O'Neill
Monday, 20 January, 2003

A proposal for an Australian-based Kangaroo Genome Project has missed out on the latest round of Australian Research Council (ARC) Research Centres of Excellence Grants, announced late last month.

Eminent molecular geneticist Prof Jennifer Marshall Graves, of the Australian National University, says she is disappointed that it will not be Australia that produces the first map, catalogue and DNA sequence of a marsupial genome.

Graves is acknowledged as one of the world's leading investigators of the genetics of sex-determination in mammal. She has made major contributions to the science of comparative genomics in man, mouse, marsupials and monotremes.

Although the ARC has advised her it that hopes to help the research centres on its reserve list to find alternative sources of income, Graves said she feared that any delay would mean that Australia will lose its opportunity to organise and direct the world's first marsupial genome project. The project is now likely to be taken up by a team at Washington University's genome centre, which has been active in mammal genomics -- and its chosen subject may not even be an Australian marsupial.

"Most people in the field prefer the tammar wallaby, because a lot of work has been done internationally on tammar genetics, physiology and reproduction," Graves said. "But if Australia is not participating in a marsupial genome project, an American marsupial may well get the nod.

"Some US researchers work on Monodelphis domestica, the South American short-tailed opossum. It's only very distantly related to kangaroos and other Australian marsupials, so it wouldn't help us much."

US sympathy

Graves said many of her American colleagues felt it would be "a real shame" if Australia did not play a critical role in a marsupial genome project, because they understood how important it would be for Australia.

"We'll obviously continue our work here on marsupial genetics, but we risk being cut out of the action -- if we produce the marsupial genome map, we're in the loop for everything," she said.

"The map would tell us where the genes are, and how they the line up with human genes. We can look at a region of tammar chromosome, identify the genes in it, and compare them immediately to the corresponding regions in human and mouse.

"The sequence data will be publicly available, no matter who does it, but being in charge of the map would put us in the pilot's seat for everything else.

"We need to ask where we want to be in the world. Don't we want to push our own thing, and work on something uniquely Australian?"

Graves said the kangaroo genome was an untapped resource -- the eminent marsupial biologist Hugh Tyndale-Biscoe likens it to astronomers exploring the southern skies. Because marsupials are distantly related to humans, they can contribute uniquely to DNA sequence comparisons that identifies human genes and the DNA promoters that regulate their activity. She says the sex chromosomes are among the many unique features of the marsupial genome. The tammar Y-chromosome is vestigial -- the smallest of any mammal -- and preserves a history of what happens to genes, genomes and chromosomes after become isolated in highly divergent species.

"We also know now that both the X and Y chromosomes are very special, particularly in humans," she said.

In addition to the sex-chromosomes carrying genes involved in sex-determination and reproduction, the human X carries many genes that influence intelligence -- perhaps because 'brain' genes have been subjected to such intense sexual selection in humans.

Comparisons between human and tammar X chromosomes should illuminate the evolution and nature of humans' great intelligence.

Graves speculated that the Kangaroo Genome Project application missed out in this year's grants because it did not attract major funding from industry and other sources: it is difficult, in Australia's current investment climate, to attract some $AUD5 million in non-ARC funding when the commercial outcomes are far, far downstream.

The future of marsupial genomics may therefore lie in America. "It took me more than three months to prepare the application to the ARC, and I can't afford another whole year trying to find more," Graves said.

"Finding money for research isn't what I do best. I'm a molecular geneticist and I want to get stuck into comparative genomics of marsupials -- whoever produces the maps and sequences."

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