A14 Comprehensive characterisation and evolutionary analysis of endogenous retroviruses in the mouse genome

It is well established that the genome of the mouse (Mus musculus musculus) contains large numbers of transposable elements, including many endogenous retroviruses (ERVs). Murine ERV lineages have been characterized piecemeal, but a comprehensive analysis has yet to be implemented. In this study, we address this by combining high-throughput in silico screening of the mouse genome with in-depth phylogenetic analysis of murine ERVs. Based on phylogenetic analysis of ERV polymerases, we establish the presence of at least 22 major ERV lineages in the murine genome, of which only 14 have been previously described. The majority of the previously unreported lineages are relatively low copy number (<100). Using a combination of automated and manual approaches we were able to recover representative internal regions and long terminal repeats (LTRs) for four of the eight novel lineages. LTR sequences were used to infer calibrated timelines of ERV invasion and intragenomic expansion within the mouse genome. These data were transposed against a timeline of murine evolution and phylogeography, providing new insights into the coevolutionary relationships between mice and retroviruses. In particular, we establish the presence of a more ancient ERV component in the murine genome, comprised of isolated, highly degraded insertions. These sequences evidence a transition in murine evolutionary history, beginning about one million years ago, wherein the ancient ERV families that have counterparts in humans and other large mammals were overtaken by a wave of newly acquired and/or transpositionally active ERVs.