Multiple Eurasian Origins and Admixture Shaped the Genomic Legacy of the House Mouse Invasion in Africa.

Commensal mammals offer unique opportunities to study how human-mediated dispersal, admixture, and secondary contact shape genomic variation during range expansion, yet for one of the most successful invasive commensals globally, the western house mouse Mus musculus domesticus, invasion dynamics across Africa remain largely unexplored. Here, we present a large-scale population genomic analysis of 380 whole-genome sequences, including 303 newly sequenced low-coverage genomes, of which 216 are from 13 distinct African populations, enabling us to investigate how human-mediated dispersal and secondary contact with native species shape the genomic legacy of a commensal mammal invasion. Ancestry analyses reveal contributions from at least three major Eurasian source lineages contributing to African populations: an Iberian-West Asian lineage present in Morocco, Algeria, and Niger; a Mediterranean lineage represented in Tunisia; and a Northern European lineage dominant in West and Central Africa. Demographic inferences indicate both recent and ancient episodes of divergence and population contraction. In West and Central Africa, divergence times broadly overlap with European maritime expansion and colonial trade. In contrast, North African populations exhibit older coalescent signals, consistent with early participation in the western Mediterranean radiation. We also detect substantial introgression from the native Mus spretus into North African populations in regions of sympatry. Collectively, our results reveal that the African invasion of the house mouse was not a single demographic process but a mosaic of population-specific histories shaped by multiple introductions, shifting connectivity through time, admixture, and interspecific gene flow. These findings reinforce the importance of population-level perspectives in invasion genomics, especially for commensal mammals whose dispersal is closely tied to human movement, and establish the most extensive open genomic resource for wild African house mice.