preprint · bioRxiv (Cold Spring Harbor Laboratory)
The recent expansion of the western house mouse across Africa offers valuable insight into how species adapt genetically to novel environments during biological invasions. An investigation using whole-genome sequences from 218 wild mice across Europe and Africa evaluated genomic signatures of natural selection alongside gene flow from the congeneric species Mus spretus. Analyses revealed candidate genomic regions enriched for immune response, epithelial-barrier integrity, chemosensory perception, and neural development, with environmental associations primarily linked to precipitation. Most candidate regions were non-coding, indicating a predominantly regulatory and polygenic basis for adaptation. While gene sharing with Mus spretus was detected, overlapping signals between introgression and selection were limited and often predated the colonisation of Africa. Consequently, adaptive responses during the African expansion were driven mostly by standing variation within the house mouse itself, complemented by a modest contribution from introgressed alleles.
Understanding the genetic mechanisms driving species invasions clarifies how animals rapidly adapt to unfamiliar habitats and climatic conditions. By revealing that regulatory variation and ancestral interspecies mating helped house mice colonise Africa, this research improves broader comprehension of evolutionary resilience, environmental adaptation, and the genetic architecture governing complex physiological and ecological traits in mammalian populations.
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How species adapt to novel environments following biological invasion remains a central question in evolutionary biology. The recent human-mediated expansion of the western house mouse (Mus musculus domesticus) across Africa provides an opportunity to investigate the genomic basis of these rapid evolutionary responses. Using whole-genome data from 218 wild mice sampled across Europe and Africa, we combined complementary genome-wide differentiation, genotype-environment association, haplotype-based selection, and localized introgression analyses to investigate genomic signatures of selection and assess the contribution of interspecific gene flow from the native congener Mus spretus to these patterns. Genome-wide differentiation analyses identified candidate regions enriched for immune and epithelial-barrier functions, chemosensory perception, and neural or developmental pathways. Genotype-environment association analyses recovered fewer candidates linked mainly to precipitation, whereas haplotype-based scans highlighted recent selective signals involving sensory, immune, and neural functions. Across analyses, candidate regions were dominated by non-coding variation, supporting a predominantly regulatory and likely polygenic genomic architecture. Although excess allele sharing with M. spretus varied among populations, overlap between introgression and selection candidates was limited but greater than expected by chance. Several overlapping regions were also present in European populations, indicating that introgressed variants likely predated African colonization. Overall, our results suggest that the genomic signatures accompanying the African expansion of house mice were driven mainly by selection on M. m. domesticus variation, whereas introgressed M. spretus alleles contributed to a smaller subset of candidate loci and may have played a role in adaptation in African populations.
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DOI: 10.64898/2026.08.14.744291
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