Heterogeneous genetic make-up of Japanese house mice (Mus musculus) created by multiple independent introductions and spatio-temporally diverse hybridization processes

In this study, phylogenetic analysis of relatively long sequences of mitochondrial DNA (4225 bp) in the Japanese house mouse Mus musculus provides the first evidence that both southern Asian subspecies of Mus musculus castaneus (CAS) and northern Asian subspecies of Mus musculus musculus (MUS) arrived in Japan through rapid population expansion events, from Southern China similar to 4000 years ago and the Korean Peninsula similar to 2000 years ago, respectively. Nuclear DNA haplotype structure analyses targeting a chromosome region with two different tract sizes, 1 and 5 Mb, consisting of nine and six tandemly arranged markers, respectively, yielded a possible average fragment length of 170 kb of CAS haplotypes in the MUS background genome in northern Japan, providing a rough estimate of its elapsed time of 815 generations under an assumption of continued backcrossing. Less frequent and shortened CAS-like haplotypes specific to Japan were detected, suggesting ancient introduction prior to the appearance of the South Chinese CAS in Japan. Our analyses also showed sporadic appearance of long fragments (2-5 Mb) from the west European subspecies Mus musculus domesticus, indicating contemporary stowaway introduction. Overall, multiple overseas introductions, and the time-lagged inter-subspecies genetic admixture, probably resulted in the heterogeneous state of Japanese wild mice.