The demographic history of house mice (Mus musculus domesticus) in eastern North America.

The Western European house mouse (Mus musculus domesticus) is a widespread human commensal that has recently been introduced to North America. Its introduction to the Americas is thought to have resulted from the transatlantic movements of Europeans that began in the early 16th century. To study the details of this colonization history, we examine population structure, explore relevant demographic models, and infer the timing of divergence among house mouse populations in the eastern United States using published exome sequences from five North American populations and two European populations. For North American populations of house mice, levels of nucleotide variation were lower, and low-frequency alleles were less common than for European populations. These patterns provide evidence of a mild bottleneck associated with the movement of house mice into North America. Several analyses revealed that one North American population is genetically admixed, which indicates at least two source populations from Europe were independently introduced to eastern North America. Estimated divergence times between North American and German populations ranged between ∼1,000 and 7,000 years ago and overlapped with the estimated divergence time between populations from Germany and France. Demographic models comparing different North American populations revealed that these populations diverged from each other mostly within the last 500 years, consistent with the timing of the arrival of Western European settlers to North America. Together, these results support a recent introduction of Western European house mice to eastern North America, highlighting the effects of human migration and colonization on the spread of an invasive human commensal.

The genomic basis of high-elevation adaptation in wild house mice (Mus musculus domesticus) from South America.

Understanding the genetic basis of environmental adaptation in natural populations is a central goal in evolutionary biology. The conditions at high elevation, particularly the low oxygen available in the ambient air, impose a significant and chronic environmental challenge to metabolically active animals with lowland ancestry. To understand the process of adaptation to these novel conditions and to assess the repeatability of evolution over short timescales, we examined the signature of selection from complete exome sequences of house mice (Mus musculus domesticus) sampled across two elevational transects in the Andes of South America. Using phylogenetic analysis, we show that house mice colonized high elevations independently in Ecuador and Bolivia. Overall, we found distinct responses to selection in each transect and largely nonoverlapping sets of candidate genes, consistent with the complex nature of traits that underlie adaptation to low oxygen availability (hypoxia) in other species. Nonetheless, we also identified a small subset of the genome that appears to be under parallel selection at the gene and SNP levels. In particular, three genes (Col22a1, Fgf14, and srGAP1) bore strong signatures of selection in both transects. Finally, we observed several patterns that were common to both transects, including an excess of derived alleles at high elevation, and a number of hypoxia-associated genes exhibiting a threshold effect, with a large allele frequency change only at the highest elevations. This threshold effect suggests that selection pressures may increase disproportionately at high elevations in mammals, consistent with observations of some high-elevation diseases in humans.

Global analysis of mutations driving microevolution of a heterozygous diploid fungal pathogen.

Candida albicans is a heterozygous diploid yeast that is a commensal of the human gastrointestinal tract and a prevalent opportunistic pathogen. Here, whole-genome sequencing was performed on multiple C. albicans isolates passaged both in vitro and in vivo to characterize the complete spectrum of mutations arising in laboratory culture and in the mammalian host. We establish that, independent of culture niche, microevolution is primarily driven by de novo base substitutions and frequent short-tract loss-of-heterozygosity events. An average base-substitution rate of ∼1.2 × 10-10 per base pair per generation was observed in vitro, with higher rates inferred during host infection. Large-scale chromosomal changes were relatively rare, although chromosome 7 trisomies frequently emerged during passaging in a gastrointestinal model and was associated with increased fitness for this niche. Multiple chromosomal features impacted mutational patterns, with mutation rates elevated in repetitive regions, subtelomeric regions, and in gene families encoding cell surface proteins involved in host adhesion. Strikingly, de novo mutation rates were more than 800-fold higher in regions immediately adjacent to emergent loss-of-heterozygosity tracts, indicative of recombination-induced mutagenesis. Furthermore, genomes showed biased patterns of mutations suggestive of extensive purifying selection during passaging. These results reveal how both cell-intrinsic and cell-extrinsic factors influence C. albicans microevolution, and provide a quantitative picture of genome dynamics in this heterozygous diploid species.