Whole-genome sequencing analysis of wild-caught house mice Mus musculus from Madagascar 1

22 In Madagascar, the house mouse ( Mus musculus ) is thought to have colonized with human 23 activities and is now one of the most abundant rodents on the island. In this study, we determined the 24 whole-genome sequences of five Madagascar house mice captured from the wild. We examined the 25 evolutionary history of the population by analyzing the mitochondrial and autosomal genomes. We 26 confirmed that the mitochondrial genome lineages of Madagascar house mice formed a monophyletic 27 clade placed at one of the most basal positions in the species. An analysis of autosomal genomic 28 sequences indicates that the Madagascar house mice are genetically members of M. m. castaneus 29 (CAS), but also contain genetic elements of M. m. domesticus (DOM) resulting from hybridization 30 between subspecies. The signature of a strong population bottleneck 1000–3000 years ago was 31 observed in both mitochondrial and autosomal genomic data. All samples showed strong genetic 32 affinity to many CAS samples across a wide range of Indian Ocean coastal and island regions, with 33 divergence time estimated around 4000 years ago. These findings support that the Madagascar house 34 mice started to colonize the island with human agricultural activity, and experienced complex history 35 for the establishment. 36