The origin, inter-subspecies hybridization and genomic basis of adaptation of house mice (Mus musculus) were not well-resolved. Population genomic analyses with 349 samples from Eurasia confirmed the Pakistan-Himalaya-India junctional region as the origin centre. The divergence of Mus musculus domesticus, M. m. musculus and M. m. castaneus occurred during different interglacial stages beginning ~350 thousand years ago. Long-distance introgression from musculus into castaneus and from castaneus into musculus occurred in southern and northern China, respectively. Genomic introgression in hybrids from Europe and East Asia revealed that genomic differentiation, recombination rate, and biological functions of genes determined the introgression capability of distinct genomic regions. Unidirectional introgression of the Y chromosome made all wild mice in East Asia holding the musculus-type Y chromosome. Analyses on selective sweeps in the three subspecies elucidate the genomic basis of adaptation during spread. Our data provide novel insights into the origin and evolution of house mice.
