Of Mice and Men: Scientists unveil complete genome sequence of the mouse

Genetically speaking, what distinguishes a man from a mouse? U.S. and European scientists provide the answer in this week’s PLoS Biology. They have described the finished genome sequence of the mouse, which, after the human, is only the second mammal to have its complete genome decoded.

Researchers at Washington University in St. Louis lent their expertise to the international sequencing effort. Together, the scientists have uncovered more genetic differences between the two species than had been previously thought. About 20 percent of the mouse genes are new copies that have emerged in the past 90 million years, and they likely account for many of the features that distinguish human biology from mouse biology.

That humans and mice have 80 percent of their genes in common – and that all these genes have been identified – enhances scientists’ abilities to tease apart the mouse genes that are most closely linked to human disease.

“The complete sequence data will be extremely important to scientists studying human diseases,” says Richard K. Wilson, Ph.D., director of Washington University’s Genome Center. “The mouse is the premier animal model for Alzheimer’s, cancer, diabetes and many other diseases.”

Washington University genome scientists have guided the mouse genome project since its inception in 1999. They constructed the physical map of the mouse DNA, an important first step in isolating and sequencing the 20,210 genes that make up the animal’s genome. The team also contributed to the DNA sequencing and the analysis of the data.

The new effort builds on a previous draft version of the mouse genome, published in 2002, to reveal a vast treasury of new genes. Many of these newly discovered genes are evolving at an unusually rapid pace, probably as a result of an evolutionary “arms race” among mice and their reproductive cells.

“We now know the earlier picture of the mouse genome was incomplete,” says LaDeana Hillier, Ph.D., who worked with Wilson on the project. “By filling in the missing pieces, we realized we had initially missed a lot of genes in mice that are not found in humans. This additional information also provides a more complete understanding of mouse biology and evolution.”

The newly published mouse genome analysis was led by Deanna Church, Ph.D., of the National Center for Biotechnology Information at the National Institutes of Health and Chris Ponting, Ph.D., of the University of Oxford.

The research was supported, in part, by the National Human Genome Research Institute.

Church, DM, Goodstadt L, Hillier LW, Zody MC, Goldstein S, Xinwe S, Bult CJ, Agarwala R, Cherry JL, DiCuccio M, Hlavina W, Kapustin Y, Meric P, Maglott D, Birtle Z, Marques AC, Graves T, Zhou S, Teague B, Konstantinos P, Churas C, Place M, Herschleb J, Runnheim R, Forrest D, Amos-Landgraf J, Schwartz DC, Cheng Z, Lindblad-Toh K, Eichler EE, Ponting CP. Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biology. May 26, 2009.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.