Evolutionary dynamics of polymorphic endogenous retrovirus insertions across wild house mouse populations

Endogenous retroviruses represent a major source of structural variation in mammalian genomes, yet their diversity in wild populations remains poorly understood. Here, we conduct a comprehensive genome-wide survey of nonreference endogenous retrovirus insertions in wild house mice (Mus musculus) to characterize their distribution and evolutionary dynamics. Using a newly developed, computationally efficient bioinformatics pipeline, we detected and annotated over 100,000 nonreference endogenous retrovirus insertions from short-read sequencing data across 163 wild mouse genomes sampled across Eurasia. Our analyses revealed marked differences in endogenous retrovirus insertion patterns among subspecies and populations, including variation in genomic localization and population-specific polymorphisms. These heterogeneous patterns suggest distinct evolutionary histories and host-retrovirus interactions across populations. As a case study, we describe the distribution of the endogenous retrovirus-derived Fv4 gene, which is absent in the mouse referenece genome and confers resistance to murine leukemia viruses. Several lines of evidence showed that the spread of Fv4 insertions in Korean population has been driven by adaptive introgression from neighboring populations. Our study provides the first large-scale population genomic scan of endogenous retrovirus diversity in wild house mice. By cataloging extensive polymorphism in nonreference endogenous retrovirus insertions, our results highlight the role of endogenous retroviruses as dynamic genomic elements that contribute to structural variation and adaptive evolution.