The origin, divergence and inter-subspecies hybridization of house mice ( Mus musculus )

Abstract House mice ( Mus musculus ) are the ancestors of laboratory mouse strains and an excellent model for evolutionary biology. The origin, divergence and inter-subspecies hybridization of the three main subspecies ( Mus musculus domesticus , M. m. musculus , M. m. castaneus ) were not well-resolved. Population genomic analyses with 349 samples from Eurasia confirmed the Himalayas-India-Pakistan junctional region as the origin centre. The divergence of M. m. domesticus , M. m. musculus and M. m. castaneus occurred ∼333.6, 308.3 and 134.4 thousand years ago, respectively, which located in different interglacial stages in Pleistocene. Hybridization among M. m. domesticus , M. m. musculus , and M. m. castaneus after secondary contact during spread and gene flow between the ancestral population and different subspecies produced distinct genomic mixtures in populations from different regions of Eurasia. Long-distance introgression from M. m. musculus into M. m. castaneus and from M. m. castaneus into M. m. musculus happened in southern China and northern China, respectively. And extensive genomic introgression occurred on both autosomes and the X chromosomes. Genomic introgression in hybrids from East Asia and Europe revealed that the level of genomic differentiation, recombination rate and benefits for the survival and reproduction of hybrids determined the introgression capability of distinct genomic regions in inter-subspecies hybridization of house mice. Unidirectional introgression of the Y chromosome made all wild mice in East Asia hold the musculus -type Y chromosome. Our study provided comprehensive insights into the origin, divergence and inter-subspecies’ genomic introgression of house mice.