It may lack the charisma of a koala or a kangaroo, but the gray short-haired opossum has now earned its place in history as the first marsupial to have its DNA deciphered. One of a few creatures that gives birth to highly immature young that then are nourished--often in pouches--outside the womb, the opossum stands in sharp contrast to the other mammals--such as human, mouse, chimpanzee, and macaque--with sequenced genomes. Although its 3.4 billion bases reveal some differences with placental mammals, the opossum's immune system is surprisingly sophisticated, an international team reports today.
Unraveling the genomes of dozens of animals with varying degrees of relatedness is key to learning how humans evolved. Researchers decided to sequence this opossum, Monodelphis domestica, in part because marsupials branched off the mammalian evolutionary tree 180 million years ago. In addition, this species is used in immunology, developmental biology, and biomedical research.
The marsupial's genome holds some surprises. Reporting today in Nature, a team led by Tarjei Mikkelsen and Kerstin Lindblad-Toh of the Broad Institute of the Massachusetts Institute of Technology and Harvard in Cambridge, Massachusetts, shows that of the marsupial's 19,000 or so genes, more than 15,000 clearly correspond to human genes, including an unexpected number important to the body's defenses. That's intriguing, the researchers say, because the marsupial immune system is supposed to be primitive.
Instead, a paper in Genome Research describes many complex immunity genes normally associated with placental mammals, including those for interleukins and interferons, as well as for receptors used by natural killer- and T cells. Moreover, the opossum has a unique gene for a T-cell receptor that's active early in development before the conventional T-cell receptor genes are turned on, indicating opossum-specific advances in the complexity of immune defenses. "We can now see that the common ancestor of marsupials and [placental mammals] had all the basic building blocks that now make up the human immune system," says co-author Katherine Belov of the University of Sydney in Australia.
Other aspects of the opossum's genome, however, reveal important differences. The opossum lacks about 400 genes found in humans, for example. A key one is called XIST, which in females codes for RNA that helps deactivate the second X chromosome. Both marsupials and placental mammals do this to ensure the right amount of activity by X chromosome genes (ScienceNOW, 22 March). The fact that the opossum lacks XIST indicates XIST is a recent invention, says Jennifer Graves, a co-author of the Nature paper at the Australian National University in Canberra. "This means we have to rethink the [ancestral] gene silencing mechanism," says Graves.
Overall, the sequencers found that the genetic innovations that led to modern placental mammals were not new genes but changes in regulatory DNA and other noncoding elements. The researchers calculate that 20% of key noncoding elements in the placental genomes arose after the split from marsupials. Many of these elements appear to have arisen from transposable elements, replicating pieces of DNA that proliferate in genomes.
"The availability of the opossum genome sequence in [this] level of detail is a stunning advance in mammalian biology," says Norman Saunders, a developmental neurobiologist at University of Melbourne, Australia. In addition to helping researchers understand mammalian evolution, the work provides important clues for research in many areas of biology, adds Elizabeth Deane, an immunologist from Macquarie University in Sydney, Australia. "The next step is to take this information to the bench."