Transposable element variation inferred from long-read sequences in wild house mice from temperate and tropical environments

Abstract

Transposable elements (TEs) constitute a large fraction of mammalian genomes yet their contribution to variation among individuals within natural populations remains largely unexplored. While most TE insertions are deleterious, some may be beneficial and contribute to adaptation. We characterized TE variation and assessed its potential adaptive role using long-read whole-genome sequencing of wild-caught house mice (Mus musculus domesticus) sampled from two populations inhabiting contrasting temperate and tropical environments and differing in morphology, physiology, and behavior. We sequenced 10 mice from each population and created highly contiguous de-novo genome assemblies for each individual, allowing us to identify TEs that are not present in the mouse reference genome and to characterize individual variation. By performing manual TE curation, we identified 506 non-redundant TE consensus sequences among all mice. On average, each wild mouse genome contained 1.47 million TE insertions, ~4% of which were polymorphic among individuals. A small fraction of these polymorphic TE insertions were present in high frequency in just one of the populations, consistent with positive natural selection. Using liver RNA-seq in natural populations and in laboratory crosses, we studied gene expression at genes adjacent to polymorphic TEs. This identified a small set of TEs that are associated with the expression of nearby genes in a population-specific manner, nearly all of which showed independent signatures of positive selection. Together, these results provide the first detailed assessment of TE variation in natural populations of house mice and identify a small set of TE insertions that likely contribute to environmental adaptation.