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Genome-wide patterns of differentiation among house mouse subspecies.

ABSTRACT: One approach to understanding the genetic basis of speciation is to scan the genomes of recently diverged taxa to identify highly differentiated regions. The house mouse, Mus musculus, provides a useful system for the study of speciation. Three subspecies (M. m. castaneus, M. m. domesticus, and M. m. musculus) diverged ?350 KYA, are distributed parapatrically, show varying degrees of reproductive isolation in laboratory crosses, and hybridize in nature. We sequenced the testes transcriptomes of multiple wild-derived inbred lines from each subspecies to identify highly differentiated regions of the genome, to identify genes showing high expression divergence, and to compare patterns of differentiation among subspecies that have different demographic histories and exhibit different levels of reproductive isolation. Using a sliding-window approach, we found many genomic regions with high levels of sequence differentiation in each of the pairwise comparisons among subspecies. In all comparisons, the X chromosome was more highly differentiated than the autosomes. Sequence differentiation and expression divergence were greater in the M. m. domesticus-M. m. musculus comparison than in either pairwise comparison with M. m. castaneus, which is consistent with laboratory crosses that show the greatest reproductive isolation between M. m. domesticus and M. m. musculus. Coalescent simulations suggest that differences in estimates of effective population size can account for many of the observed patterns. However, there was an excess of highly differentiated regions relative to simulated distributions under a wide range of demographic scenarios. Overlap of some highly differentiated regions with previous results from QTL mapping and hybrid zone studies points to promising candidate regions for reproductive isolation.

SUBMITTER: Phifer-Rixey M

PROVIDER: S-EPMC4174939 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Genome-wide patterns of differentiation among house mouse subspecies.

Phifer-Rixey Megan M Bomhoff Matthew M Nachman Michael W MW

Genetics 20140703 1

One approach to understanding the genetic basis of speciation is to scan the genomes of recently diverged taxa to identify highly differentiated regions. The house mouse, Mus musculus, provides a useful system for the study of speciation. Three subspecies (M. m. castaneus, M. m. domesticus, and M. m. musculus) diverged ∼350 KYA, are distributed parapatrically, show varying degrees of reproductive isolation in laboratory crosses, and hybridize in nature. We sequenced the testes transcriptomes of ...[more]

PMID: 24996909

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Project description: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.

Dataset Information

Genome-wide patterns of differentiation among house mouse subspecies.

Publications

Genome-wide patterns of differentiation among house mouse subspecies.

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