Nucleotide Variation in Wild and Inbred Mice

Abstract

The house mouse is a well-established model organism, particularly for studying the genetics of complex traits. However, most studies of mice use classical inbred strains, whose genomes derive from multiple species. Relatively little is known about the distribution of genetic variation among these species or how variation among strains relates to variation in the wild. We sequenced intronic regions of five X-linked loci in large samples of wild Mus domesticus and M. musculus, and we found low levels of nucleotide diversity in both species. We compared these data to published data from short portions of six X-linked and 18 autosomal loci in wild mice. We estimate that M. domesticus and M. musculus diverged ,500,000 years ago. Consistent with this recent divergence, some gene genealogies were reciprocally monophyletic between these species, while others were paraphyletic or polyphyletic. In general, the X chromosome was more differentiated than the autosomes. We resequenced classical inbred strains for all 29 loci and found that inbred strains contain only a small amount of the genetic variation seen in wild mice. Notably, the X chromosome contains proportionately less variation among inbred strains than do the autosomes. Moreover, variation among inbred strains derives from differences between species as well as from differences within species, and these proportions differ in different genomic regions. Wild mice thus provide a reservoir of additional genetic variation that may be useful for mapping studies. Together these results suggest that wild mice will be a valuable complement to laboratory strains for studying the genetics of complex traits.

Inference of Historical Changes in Migration Rate From the Lengths of Migrant Tracts

“…The sample sizes of the mouse SNP data set seemed too small for published methods for identifying ancestry along recombining chromosomes (e.g., Falush et al 2003). However, the task of tract identification is simplified by the high level of genetic differentiation between the two subspecies, which diverged perhaps 1 million generations ago and show very high levels of genetic differentiation (Baines and Harr 2007;Salcedo et al 2007). We were therefore able to use a very simple set of criteria for defining migrant tracts in these data.…”

Genetics of Rapid and Extreme Size Evolution in Island Mice

“…Second, laboratory mice have a complex history, with uncertain connections to wild mice (Silver 1995). Many genetic variants observed in natural populations are missing from the panel of commonly used inbred strains (Salcedo et al 2007), suggesting that evolution in nature and in the laboratory could involve different sets of mutations. Here, we use mice from Gough Island to provide a genetic portrait of rapid and extreme size evolution in a wild, island population.…”

Genetic Dissection of a Key Reproductive Barrier Between Nascent Species of House Mice

“…Three recognizable subspecies diverged from a common ancestor only 500,000 generations ago (She et al 1990;Boursot et al 1996;Suzuki et al 2004;Salcedo et al 2007;Geraldes et al 2008). Despite this short divergence time, several lines of evidence indicate reproductive isolation between two of the subspecies, Mus musculus musculus and Mus musculus domesticus.…”