DNA Variability and Natural Selection in House Mice and Humans

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9628942 Nachman A central goal of population genetics is to understand the forces that determine the amount and distribution of genetic variation in natural populations of organisms. The primary goal of this project is to look for evidence of natural selection in patterns of DNA sequence variation in populations of mice and humans. The second objective is to determine the relative importance of two forms of selection: the spread of new beneficial mutations, and the elimination of deleterious mutations from populations. Recent improvements in molecular techniques and statistical analyses will be used to sequence and analyze patterns of DNA variation, in 20 genes in house mice (Mus domesticus) and 10 genes in humans, as well as in two species of mice (Mus spretus and Mus caroli) closely related to the house mouse and in two primates (Orangutan and Common chimpanzee) closely related to humans. Genes from the X chromosome and from several other chromosomes will be sequenced. An important aim of this work is to determine the relationship between the amount of genetic variation at each gene and the rate of recombination (the amount of genetic mixing between the two copies of a gene in individuals). Work in fruit flies and preliminary work in mice suggests that genes with more recombination are more variable. This has important implications; for example, conservation biologists interested in estimating genetic variability in a species will need to sample genes with both high and low recombination rates. This project will provide insight into the processes affecting the amount and distribution of genetic variation in nature. This is essential not only for conservation biology but also for understanding the genetic basis of evolutionary change in any organism. Moreover, the work on humans will document the amount of genetic variability within and between different regions of the world and will provide important clues to the origins and migrations of modern humans.