May 21, 2007

Opossum Genome Shows Value in “Junk” DNA

Small opossum cupped in two hands South American grey short-tailed opossum.Paul Samollow, Southwest Foundation for Biomedical Research, San Antonio.

The opossum genome, the first marsupial genome to be sequenced, gives scientists interesting insight into human evolution.

Marsupials diverged from our ancestors about 180 million years ago. Unlike humans and other placental mammals that give birth to alert, well-developed young, marsupials are born at a very early stage of development. The young live in the safety of their mother's pouch until they have fully developed and are able to move about on their own. They're thus ideal for early developmental research.

An international team led by researchers at the Broad Institute of MIT and Harvard, began sequencing the genome of a female grey, short-tailed opossum (Monodelphis domestica) in 2003. Native to South America, this marsupial is an important animal model for research in neurobiology, cancer and developmental biology. NIH's National Human Genome Research Institute (NHGRI) funded the project.

The researchers compared the opossum genome sequence with the genomes of other mammals, including humans and mice, and reported their results in the May 10, 2007, issue of the journal Nature. The opossum genome, they found, has approximately 18,000 to 20,000 genes that code for proteins. Over 99% of these genes are also found in humans. Genes unique to the opossum were found to be involved in immunity, sensory perception and detoxification. The group also found evidence that the immune system of the opossum is more complex than originally thought.

Surprisingly, the research team discovered that most of the genomic changes believed to have played a role in human evolution are found in regions of the genome that do not code for protein. Until recently, these regions were referred to as "Junk DNA." However, scientists now know that they contain important regulatory elements that can influence the activity of nearby genes.

A large proportion of the differences in these DNA regulatory regions appear to have been caused by the activity of specialized DNA sequences called transposons, which move around in the genome and leave bits of sequence behind, earning them the moniker "jumping genes." Transposons, the researchers conclude, appear to be a major creative force in the evolution of mammalian gene regulation.

"The opossum genome occupies a unique position on the tree of life," said NHGRI Director Dr. Francis Collins. "This analysis fills a crucial gap in our understanding of how mammalian genomes, including our own, have evolved over millions of years."

These results suggest that mammals evolved more by changing when and where proteins are made than by inventing new kinds of proteins. The researchers are hopeful that sequencing the genomes of other marsupials, from both the Americas and Australia, will give them more insight into understanding how marsupials, and ultimately humans, evolved.

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