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| Dr. Matthew Breen |
The genome of the opossum is no longer playing dead, and the animal’s genetic makeup may help scientists better understand and treat neurological disorders and skin cancer in humans.
Researchers at the Broad Institute of Harvard and Massachusetts Institute of Technology, North Carolina State University and other universities and hospitals from around the world have sequenced the genome of the grey, short-tailed opossum. The results of the team’s research are published in the May 10 edition of the journal Nature.
Dr. Matthew Breen, associate professor of genomics at NC State’s College of Veterinary Medicine, and Shannon Duke, a research assistant in Breen’s laboratory, were among the scientists involved in the project. The short-tailed opossum – Monodelphis domestica – is native to South America and is the first marsupial species to have its genome sequenced, an achievement that opens additional research avenues for certain biological and medical investigations in humans.
Newborn opossums have the ability to completely heal injured sections of their spinal cords. Additionally, the opossum is the only other mammal besides humans known to be highly susceptible to melanoma – a common type of skin cancer in people – from exposure to ultraviolet rays. Understanding the biological processes behind these phenomena could yield important insights into nerve injuries, regenerative medicine and skin-cancer therapies.
“The Monodelphis offers to biomedical research something no other species can offer,” Breen says. “There are some significant medical advantages of the Monodelphis as a model system for degenerative disease and repair. Determining how their nerve fibers operate and repair themselves has huge implications for human neurological sciences.
“The occurrence of melanoma in humans and the opossum is a result of some shared genetic makeup, which also makes the Monodelphis an advantageous model for cancer research.”
Genome sequencing involves determining the exact order of an organism’s genetic information that is encoded in its DNA. The opossum genome project involved disassembling more than 3.5 billion pieces of DNA and then reassembling those pieces in the proper order. Breen and Duke played a key role in reassembling the genetic information, a process known as genome anchoring and one that Breen likens to putting the individual, unnumbered pages of a book back together.
“If the information contained in a genome is like the information contained in a book, imagine ripping out all the pages of a book that didn’t have any page numbers on them and scattering them on the floor,” Breen says. “Our role in the genome reassembly process involved putting the pages back together in the right order, stamping the page numbers on them and organizing them into chapters. It’s like we made the contents page.”
Kerstin Lindblad-Toh, co-director of the genome sequencing and analysis program of the Broad Institute, said the work done by Breen’s lab played an integral part in the project.
“The mapping of the opossum genome sequence on the chromosomes performed by Dr. Breen’s laboratory is a critical step in generating this first marsupial genome sequence,” Lindblad-Toh says. “As an analogy, Dr. Breen’s work allows us read the opossum genome sequence from a bound book rather than as a disordered loose-leaf text.”
The opossum genome project was funded by a grant from the National Human Genome Research Institute.
- austin -
Note to editors: An abstract of the Nature paper follows.
“Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences”
Authors: Tarjei S. Mikkelsen, Broad Institute of Harvard and MIT; Matthew Breen & Shannon Duke, North Carolina State University; et al.
Published: May 11, 2007, in Nature
Abstract: We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian (‘marsupial’) species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.
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