Insights into Mus musculus subspecies population structure across Eurasia revealed by whole-genome sequence analysis

For more than 100 years, house mice (Mus musculus) have been used as a key animal model in biomedical research. House mice are genetically diverse, yet their genetic background at the global level has not been fully understood. Previous molecular phylogenetic studies suggested that three major subspecies originated in South Asia and spread across the world with the migration of modern humans in prehistoric and historic times. Relatively recent migration events ([~]10,000 years ago to present) have complicated the genetic landscape of wild house mice. In this study, we sequenced the whole genomes of 98 wild house mice collected from Eurasia, particularly East Asia, Southeast Asia, and South Asia. We found that although wild house mice consist of three major genetic groups corresponding to the three major subspecies, individuals representing admixture between subspecies are much more ubiquitous than previously recognized. Furthermore, several samples showed an incongruent pattern of genealogies between mitochondrial and autosomal genomes. Using samples likely retaining the original genetic components of subspecies, we estimated the pattern and timing of divergence among the subspecies. Our results provide critical understanding of the genetic diversity of wild house mice at the global level, which may be particularly useful for future biomedical and evolutionary research.