Detection of recombinant haplotypes in wild mice (Mus musculus) provides new insights into the origin of Japanese mice

Abstract

Japanese house mice (Mus musculus molossinus) are thought to be a hybrid lineage derived from two prehistoric immigrants, the subspecies M. m. musculus of northern Eurasia and M. m. castaneus of South Asia. Mice of the western European subspecies M. m. domesticus have been detected in Japanese ports and airports only. We examined haplotype structuring of a 200 kb stretch on chromosome 8 for 59 mice from throughout Eurasia, determining short segments (approximately 370-600 bp) of eight nuclear genes (Fanca, Spire2, Tcf25, Mc1r, Tubb3, Def8, Afg3l1 and Dbndd1) which are intermittently arranged in this order. Where possible we identified the subspecies origin for individual gene alleles and then designated haplotypes for concatenated alleles. We recovered 11 haplotypes among 19 Japanese mice examined, identified either as 'intact' haplotypes derived from the subspecies musculus (57.9%), domesticus (7.9%), and castaneus (2.6%), or as 'recombinant' haplotypes (31.6%). We also detected recombinant haplotypes unique to Sakhalin. The complex nature of the recombinant haplotypes suggests ancient introduction of all three subspecies components into the peripheral part of Eurasia or complicated genomic admixture before the movement from source areas. 'Intact'domesticus and castaneus haplotypes in other Japanese wild mice imply ongoing stowaway introductions. The method has general utility for assessing the history of genetic admixture and for disclosing ongoing genetic contamination.

Completely phased genome sequencing through chromosome sorting

“…Studies of human adaptation may benefit from a better ability to determine long-range haplotypes, which are signals of recent positive selection (23,24). Determination of recombinant haplotypes provides insight into population history (25). Last but not least, Phase-Seq provides a foundation for resolving the roles of parental origin-specific genetic variants in disease association, allele-specific gene expression, and alternative splicing (1,18,19).…”

Historical Introduction of Japanese Wild Mice, Mus musculus, from South China and the Korean Peninsula

“…1C). Hybridization time has been estimated to be a thousand generations (Nunome et al, 2010), providing concrete evidence that the "recombinant" haplotypes resulted from a historical event in ancient times and were not due to stowaway introduction during the modern age. The results of mitochondrial and nuclear gene analyses allowed us to predict that two areas of the continent, South China and the Korean peninsula, are the primary source areas of Japanese wild mice.…”

“…1D). Phylogeographic analyses using nuclear genes have revealed the presence of the East European DOM within a CAS segment of the haplotypes from northern Japan, implying the presence of hidden evolutionary episodes of the CAS migration from the continent to Japan (Nunome et al, 2010) (Fig. 1D).…”

“…Our previous phylogeographic study focusing on haplotypes of linked autosomal genes highlighted the concealed evolutionary history of Japanese wild mice (Nunome et al, 2010). In that study, we examined eight linked genes in a 200 kb region of chromosome 8 and assigned the alleles into three subspecies groups (DOM, CAS, and MUS) and disclosed haplotype structures defined by the combination of the eight genes and their geographic distributions.…”

“…However, the exact geographic origins of Japanese wild mice are uncertain due to the veiled histories of subspecies groups in East Asia. From our recent phylogeographic work on mice collected over wide areas of the two subspecies groups (Nunome et al, 2010;Suzuki and Aplin, 2012;Suzuki et al, 2013), it is now possible to more accurately pinpoint the multiple places of origin of Japanese mice in the Korean Peninsula and South China. Here we describe recent achievements related to this issue and discuss the possible interpretation of the historical migrations of wild mice from continental areas to Japan.…”