The South American, grey short-tailed opossum is the first mammal to yield up the secrets of its genome.
Credit: Paul Samollow, Southwest Foundation for Biomedical Research, San Antonio.
SYDNEY: In a world first, researchers have sequenced the genome of a marsupial. The results hint at a surprising role for 'junk DNA' in mammalian evolution.
Marsupials, a group that includes koalas and kangaroos, occupy a unique evolutionary position. Placental mammals and marsupials evolved from a common mammalian ancestor, splitting around 180 million years ago – which makes a comparison between them a useful way to pinpoint unique placental DNA.
To this end an international consortium led by geneticists at the Broad Institute in Cambridge, Massachusetts, U.S., sequenced the genome of the South American, grey short-tailed opossum (Monodelphis domestica).
Junk DNA
By comparing it with the genomes of placental mammals, such as humans, mice and chimpanzees, they have uncovered new data about gene expression and the immune system of mammals.
The landmark study, published today in U.K. journal Nature, and backed up by papers in Genome Research, involved the efforts of 63 experts in immunology, genetics and marsupial biology, including 11 Australians.
"We're pretty good at identifying the protein coding genes, but the small regulatory elements – the switches that control those genes – are hard to find, the best way to do that is to compare between species to find [sequences that stay the same]," said Matthew Wakefield, a team member and geneticist with the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia.
In terms of functional genes, the opossum appears to be pretty similar to its placental relatives – many of its 18,000 to 20,000 genes have the same function as ours. More surprising is the discovery that 20 per cent of 'switches' in non-coding sequences – thought to control how genes are turned on and off – evolved in placental mammals after we split from our common ancestor with marsupials.
The research suggests that mammal genomes may have evolved as a result of rearranging non-coding or 'junk DNA' sequences outside genes, rather than by variation in functional genes that produce proteins.
As Wakefield sees it, "mammals use a common Lego set, it's just the instructions for putting them together that are different."
Human treatments
Another major discovery was that marsupial immune systems were remarkably similar to those of other mammals, including humans. "This dispels the myth that marsupial immune systems are primitive," said Kathy Belov, a marsupial immunologist at the University of Sydney.
The immune system has to evolve rapidly to keep ahead in the arms race with pathogens, she said, so immune genes change often, making them hard to identify. But comparative studies allowed the team to narrow down their search, leading to the detection in the opossum of around 1,500 genes involved in immunity.
The findings will be useful for understanding both marsupial and human development and disease.
Marsupials are born after a short gestation period, with no immune system and underdeveloped lungs. As such, they provide a model for studying development of the immune system and organ development.
"This is a really significant project," commented University of Melbourne geneticist Phil Batterham, not one of the study authors. He adds that studying the opossum could help save premature human babies with underdeveloped lungs.
Platypus and wallaby
The opossum also provides a model for the study of malignant melanoma, being the only mammal other than humans that develop the cancer from UV light alone. It could also aid research into repairing damaged spines, as newborn marsupials are able to completely regenerate damaged spinal cords.
The newly sequenced genome could aid the search for cures for some of the most devastating Australian marsupial diseases, said Belov, including Tasmanian devil facial tumours and Chlamydia outbreaks in koalas.
Two other Australian genome projects – the platypus and the tammar wallaby – are also underway. "In isolation, any one genome sequence is of limited value. It's really by comparing genome sequences that we maximise the benefit," said Batterham.
