The grey short-tailed opossum is a great model for studying human diseases, developmental biology and immunology.Larry Wadsworth, Media Resources, Texas A&M University.Such a small creature for so great an honour: the grey short-tailed opossum is the first marsupial to have its genome fully sequenced, joining a menagerie of other mammals including the mouse, rat, chimpanzee and, of course, human.
"The opossum is a wonderful comparison to the human genome," says Eric Lander, director of the Broad Institute in Cambridge, Massachusetts, and a contributor to the study, which was completed by a consortium of researchers from the United States, Australia, the United Kingdom and Canada and is presented in this week's Nature1.
Monodelphis domestica is one of about 60 species of South American tree-dwelling marsupials. It lives a solitary arboreal life in the rainforests of Bolivia, Brazil and Paraguay, and more closely resembles a rodent than its iconic Australian cousins, the koala or kangaroo. It doesn't have the trademark marsupial pouch but does, like the rest of its kin, have an extremely short gestation period — about 14 days. Its young complete their development while continuously attached to their mother.
Marilyn Renfree, deputy director for the Australian Research Council's (ARC) Centre of Excellence for Kangaroo Genomics in Melbourne, says that a marsupial sequence is particularly important because it serves as a point of reference by which to compare mammalian evolution. Marsupials and placental mammals (the group to which humans belong) diverged from one another about 180 million years ago, with each line continuing to evolve and specialize.
Gene parade
It turns out that the opossum has somewhere between 18,000 to 20,000 protein-encoding genes, approximately the same number as humans.
Like humans, the vast majority of the opossum's genes are identical to other placental mammals. But some are specific to marsupials. These include genes associated with sensory perception, detoxification and the immune system; genes that probably play an important part in adapting to specific environmental niches.
The researchers also found that as placental mammals evolved, most of the recent innovation has, surprisingly, been in the parts of DNA that don't code for proteins, rather than in the parts that do. This non-gene part of the genome is thought to be important in helping to affect the way that genes make proteins. "The secret to making mammals is less in making new genes than in making new regulations for those genes," says Lander.
A model specimen
The grey short-tailed opossum was chosen amongst all marsupials primarily because it is widely used in laboratory research as a model for studying human diseases, developmental biology and immunogenetics.
Newborn opossum pups have a remarkable ability to recover from severe spinal-cord injuries, including a completely severed cord, and so are used as a model to study regeneration of the nervous system. Jennifer Graves, director of the ARC Centre of Excellence for Kangaroo Genomics and a member of the research team, says understanding the molecular biology underlying this kind of recovery is a promising line of research in developing treatments for humans with spinal-cord injuries.
And, Graves points out, M. domestica is the only species besides humans that develops melanoma when exposed to ultraviolet radiation. Discovering the genetics involved in the development of this form of cancer, she says, would be a breakthrough in combating the human form of the disease.
Not worse, just different
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The study helps to erode a common misconception that marsupials are somehow an archaic or second-rate category of mammal, says Graves. In particular, the discovery of a gene that encodes for a unique form of T-cell receptor not found in placental mammals "knocks that assumption on its head", she says. "It shows that they have a very sophisticated immune system, but one that's very different."
Renfree, who is currently sequencing the kangaroo genome, says she's generally excited about the project. "It's fantastic," she says, "and great for the study of marsupials in general," although she says it will be important to complement the opossum genome with other marsupials. "You can't extrapolate everything about marsupials from a singles species," says Renfree. "Just like you can't extrapolate from a mouse to a man."
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