Copy number variation in house mice. CNV in mice

Copy number variation represents a major source of genetic divergence, yet the evolutionary dynamics of genic copy number variation on differentiation and adaptation in natural populations has not been much studied so far. We applied a read depth approach on genome re-sequencing data to detect copy number variants (CNVs) ≥ 1 kb in wild-caught mice belonging to four populations of M. m. domesticus. We complement the bioinformatic analyses by experimental validation through droplet digital PCR. The specific focus of our analysis are CNVs that include complete genes, as these could be expected to contribute most directly to evolutionary divergence. In total, 1,863 transcription units appear to be completely encompassed within CNVs in at least one individual when compared to the reference assembly. 179 of these show population specific copy number differences and 325 are subject to complete deletion in multiple individuals. Among the most copy-number variable genes are three highly conserved genes, encoding the splicing factor CWC22, the spindle protein SFI1 and the Holliday junction recognition protein HJURP, which show population-specific expansion patterns that suggest an involvement in local adaptations. We find that genes overlapping large segmental duplications are generally more copy-number variable. These encode proteins relevant for environmental and behavioral interactions, such as vomeronasal and olfactory receptors, as well as major urinary proteins, but also several proteins of as yet unknown function. The overall analysis shows that genic CNVs in mice contribute to population differentiation more than they do in humans and may promote and speed up population divergence.