First marsupial genome released

Most differences between the opossom and placental mammals stem from non-coding DNA

By | May 9, 2007

Most of the genetic difference between marsupials and placental mammals comes from non-coding sequences, not proteins, according to the first marsupial genome sequence, unveiled in this week's Nature. The sequence is of the South American grey short-tailed opossum Monodelphis domestica. The opossum genome "is bound to make the [evolutionary developmental biology] community very happy, because they've been saying all along that it's the regulation of genes that is what's driving the changes that we see in the evolution of animals," David Haussler of the University of California, Santa Cruz, who was not involved in the research, told The Scientist. "This paper really establishes it on a large scale." The sequence also reveals that X-inactivation works differently in the opossum than in female placental mammals. Led by Tarjei Mikkelsen of the Broad Institute in Cambridge, Mass., the researchers used the whole-genome shotgun method to sequence the genome of a single female opossum. The assembled sequence is 3,475 megabases long. The sequence reveals that opossum autosomes have low G+C content and a low long-term recombination rate. This supports a hypothesis called the biased gene conversion model, which states that high levels of recombination tend to lead to high GC content, according to Nicolas Galtier of the University of Montpellier, France, who was not involved in the work. Most sequence differences between the opossom and placental mammals appear not in protein-coding genes but in non-coding sequences, which is "evidence that the 'junk' DNA actually shapes our genome," said Haussler. The researchers found that about 20% of non-coding sequences in placental mammals evolved after their split from the marsupial lineage, and approximately 16% of non-coding sequences specific to placental mammals are clearly derived from transposons. The opossum genome "provides a powerful tool to identify the switches that turn human genes on and off, and how these switches evolved," according to Sue Forrest, director of the Australian Genome Research Facility in Parkville, who was not involved in the project. The researchers also found that the X-inactivation system found in female placental mammals is not present in the opossum, which confirms a previous finding that suggested a gene involved in X-inactivation evolved after placental mammals and marsupials diverged, according to Anne Ferguson-Smith of the University of Cambridge, UK, also not a co-author. While placental mammals randomly inactivate one X chromsome in each embryonic cell, marsupial females always inactivate the paternal X chromosome. According to co-author Jennifer Marshall Graves of The Australian National University in Canberra, the researchers originally expected that the non-coding gene XIST, which controls X-inactivation in placental mammals, would also be found in marsupials. However, they found that the opossom lacks this gene, as well as a pattern of repetitive sequences that's thought to boost the inactivation signal. "This means that we have to rethink the basic gene silencing mechanism" in marsupials, Graves told The Scientist in an Email. The opossum genome appears to contain about 20,000 protein-coding genes, the authors found, and the vast majority of these are also found in placental mammals. Among protein-coding genes specific to the opossum lineage, the researchers found gene families involved in immunity, sensory perception, detoxification, and dietary adaptations. The opossum genome also contained many previously unknown genes involved in immunity. "The discovery that the immune system has many conserved and also many lineage-specific immune genes is important," according to Marilyn Renfree of the University of Melbourne, Australia, who was not a co-author. After struggling to clone marsupial immunity genes, scientists speculated that marsupials "did not have a well developed immune system," Renfree explained. Sequences of an Australian marsupial and a monotreme will provide even more insight into mammalian evolution, Ferguson-Smith told The Scientist in an Email. Genome projects for the tammar wallaby and the platypus are already underway. Further analyses of the opossum genome architecure, gene evolution, and immune system are published in this week's Genome Research. Melissa Lee Phillips Links within this article T.S. Mikkelsen, "Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences," Nature, May 10, 2007. David Haussler T.M. Powledge, "Shotgun sequencing comes of age," The Scientist, December 31, 2002. L. Duret et al., "A new perspective on isochore evolution," Gene, December 30, 2006. Sue Forrest L. Duret et al., "The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene," Science, June 16, 2006. Anne Ferguson-Smith E. Heard, "Recent advances in X-chromosome inactivation," Current Opinion in Cell Biology, June 2004. J.L. VandeBerg et al., "X-chromosome inactivation and evolution in marsupials and other mammals," Isoenzymes, 1983. Jennifer Marshall Graves M.F. Lyon, "Do LINEs have a role in X-chromosome inactivation?" Journal of Biomedicine & Biotechnology, 2006. Marilyn Renfree T.M. Powledge, "How many genomes are enough?" The Scientist, November 17, 2003. Tammar Wallaby Genome Project Duck-Billed Platypus genome sequencing A.J. Gentles et al., "Evolutionary dynamics of transposable elements in the short-tailed opossum Monodelphis domestica," Genome Research, published online May 10, 2007. L. Goodstadt et al., "An analysis of the gene complement of a marsupial, Monodelphis domestica: evolution of lineage-specific genes and giant chromosomes," Genome Research, published online May 10, 2007. K. Belov et al., "Characterization of the opossum immune genome provides insights into the evolution of the mammalian immune system," Genome Research, published online May 10, 2007.

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