Ancient onset of geographical divergence, interpopulation genetic exchange, and natural selection on theMc1rcoat-colour gene in the house mouse (Mus musculus)

Abstract

We examined genetic variation in house mice from India and Pakistan, a predominant part of the predicted homeland of this species and also the territory of the subspecies Mus musculus castaneus (CAS), using a nuclear marker for seven tandemly arranged genes (Fanca–Spire2–Tcf25–Mc1r–Def8–Afg3l1–Dbndd1) and compared them with those previously determined for mice from other parts of Eurasia. Construction of a network with the concatenate sequences yielded three distinct clusters representing the three major subspecies groups: CAS, Mus musculus domesticus (DOM) and Mus musculus musculus (MUS). STRUCTURE analysis provided evidence for further subdivision of CAS into two main haplogroups within the Indian subcontinent. Single-gene networks revealed not only gene-specific architecture for subgrouping in CAS, but also allelic exchange among subspecies. These results suggest the earlier onset of allopatric divergence in the predicted homeland (the Middle East and Indian subcontinent) and subsequent intermittent admixing via gene flow across the CAS haplogroups and among the three subspecies groups. A comparison of the levels of nucleotide diversity among the gene regions revealed a less divergent state in the chromosome region containing Mc1r and its adjacent genes, indicative of a selective sweep, suggesting the involvement of natural selection in the Mc1r allelic variation.