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Abstract:
General parameters of selection, such as the frequency and strength of positive selection in natural populations or the role
of introgression, are still insufficiently understood. The house mouse (Mus musculus) is a particularly well-suited model
system to approach such questions, since it has a defined history of splits into subspecies and populations and since
extensive genome information is available. We have used high-density single-nucleotide polymorphism (SNP) typing arrays
to assess genomic patterns of positive selection and introgression of alleles in two natural populations of each of the
subspecies M. m. domesticus and M. m. musculus. Applying different statistical procedures, we find a large number of
regions subject to apparent selective sweeps, indicating frequent positive selection on rare alleles or novel mutations.
Genes in the regions include well-studied imprinted loci (e.g. Plagl1/Zac1), homologues of human genes involved in
adaptations (e.g. alpha-amylase genes) or in genetic diseases (e.g. Huntingtin and Parkin). Haplotype matching between the
two subspecies reveals a large number of haplotypes that show patterns of introgression from specific populations of the
respective other subspecies, with at least 10% of the genome being affected by partial or full introgression. Using neutral
simulations for comparison, we find that the size and the fraction of introgressed haplotypes are not compatible with a pure
migration or incomplete lineage sorting model. Hence, it appears that introgressed haplotypes can rise in frequency due to
positive selection and thus can contribute to the adaptive genomic landscape of natural populations. Our data support the
notion that natural genomes are subject to complex adaptive processes, including the introgression of haplotypes from
other differentiated populations or species at a larger scale than previously assumed for animals. This implies that some of
the admixture found in inbred strains of mice may also have a natural origin.
