An international team, led by researchers at the Broad Institute of MIT and Harvard and supported by the National Institutes of Health (NIH) announced the publication of the first genome sequence of a marsupial, belonging to a South American species of opossum.
In a comparison of the marsupial genome to genomes of non-marsupials, including human, published in the May 10 issue of the journal Nature, the team found that most innovations leading to the human genome sequence lie not in protein-coding genes, but in areas that until recently were referred to as junk DNA.
The effort to generate high-quality genome sequence of the gray short-tailed, South American opossum, Monodelphis domestica, began in 2003 and cost approximately $25 million.
The sequencing work was funded by the National Human Genome Research Institute (NHGRI), part of the NIH, and carried out at the Broad Institute Sequencing Platform, which is a member of NHGRI's Large-Scale Sequencing Research Network.
"The opossum genome occupies a unique position on the tree of life. This analysis fills a crucial gap in our understanding of how mammalian genomes, including our own, have evolved over millions of years," said NHGRI Director Francis S. Collins, M.D., Ph.D.
"These new findings illustrate how important it is to understand all of the human genome, not just the fraction that contains genes that code for proteins. We must identify all functional elements in the genome if we are to have the most complete toolbox possible to explore human biology and improve human health."
Marsupials are unique among mammals because their young are born at an extremely early stage of development, attach to their mother's teats and complete their subsequent development while in a protective pouch. This makes the young readily available for early developmental research.
The opossum genome sequence also provides researchers with a fresh perspective on the evolutionary origins of the human genome. It sheds light on the genetic differences between placental mammals, such as humans, mice and dogs; and marsupial mammals, such as opossums and kangaroos.
"Marsupials are the closest living relatives of placental mammals. Because of this relationship, the opossum genome offers a unique lens though which to view the evolution of our own genome," said Kerstin Lindblad-Toh, Ph.D., the study's senior author and co-director of the Broad Institute's genome sequencing and analysis program and the study's senior author.
Marsupials and the ancestors of placental mammals diverged 180 million years ago. By comparing the opossum and human genomes, researchers were able to pinpoint genetic elements that are present in placental mammals, but missing from marsupials - that is, the genetic factors that may underlie many of the differences between the two types of mammals.
Interestingly, about one-fifth of the key functional elements in the human genome arose during this relatively recent evolutionary period. By focusing on the recent innovations, the scientists made two major findings:
- First, the vast majority (about 95 percent) of recent genetic innovation lies not in protein-coding genes, but in regions of the genome that do not contain genes and that many had referred to as junk DNA until recently. Researchers now know that junk DNA may contain regulatory elements that influence the activity of nearby genes, but the full extent of the importance of these non-gene regions is still being revealed. The new results suggest that mammals evolved not so much by inventing new kinds of proteins, as by tweaking the molecular controls that dictate when and where proteins are made.
- Second, many of the new DNA instructions appear to be derived from transposons, or "jumping genes," which are also located in areas once thought to be junk DNA. When the human genome was compared to the opossum's, researchers discovered that at least 16 percent of transposon-derived sequences had mutated beyond the point of recognition.
"Transposons have a restless lifestyle, often shuttling themselves from one chromosome to another," said the study's first author Tarjei Mikkelsen, a Broad Institute researcher. "It is now clear that in their travels, they are disseminating crucial genetic innovations around the genome."