DNA Variability and Genetic Hitchhiking in Mus

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9306493 Nachman A central goal of population genetics is to understand the process that shape genetic variation in natural populations of organisms. An important phenomenon, knows as genetic hitchhiking, involves the interaction of natural selection and genetic recombination (genetic mixing between the two copies of a gene). When a particular DNA mutation is favored by natural selection, it may become more common in a population since individuals with the mutation will replace individuals without it. However, when natural selection favors a particular DNA site, it will also affect nearby DNA sites which are not themselves under selection. Typically, genetic hitchhiking will cause a reduction in DNA variability at these nearby sites. The amount of reduction depends on the rate of recombination. This relationship is important because it allows us to look for evidence of natural selection by comparing levels of DNA variability in genes with different recombination rates. Recent studies on fruit flies (Drosophila) have demonstrated that genetic hitchhiking may affect a large portion of the genome. This has broad significance for genome evolution, including the implication that natural selection may be acting quite frequently.%%% To learn if these findings represent a general aspect of molecular evolution, this study will look for evidence of genetic hitchhiking in the house mouse, Mus domesticus. This will be achieved by comparing levels of DNA sequence variation among four important genes on the X-chromosome: two with high recombination rates (Pip and Amg), and two with lower recombination rates (Hprt and G6pd). If genetic hitchhiking is common, then the two genes with a high recombination rate should show a greater amount of DNA sequence variability than the two genes with a low recombination rate. Three of these four genes in mice serve as important models for human genetic diseases (Hprt: Lesch-Nyhan syndrome; G6pd: hemolytic anemia: Plp: P elizaeus-Merzbacher disease).