Abstract
Both exogenous and endogenous retroviruses have long been studied in mice, and some of the earliest mouse studies focused on the heritability of genetic factors influencing permissivity and resistance to infection. The prototypic retroviral restriction factor,Fv1, is now understood to exhibit a degree of control across multiple retroviral genera and is highly diverse withinMus. To better understand the age and evolutionary history ofFv1, a comprehensive survey of the Muroidea was conducted, allowing the progenitor integration to be dated to ∼45 million years. Intact coding potential is visible beyondMus, and sequence analysis reveals strong signatures of positive selection also within field mice,Apodemus.Fv1’s survival for such a period implies a recurring and shifting retroviral burden imparting the necessary selective pressures—an influence likely also common to analogous factors. Regions ofFv1adapt cooperatively, highlighting its preference for repeated structures and suggesting that this functionally constrained aspect of the retroviral capsid lattice presents a common target in the evolution of intrinsic immunity.
Funder
Francis Crick Institute
National Science Foundation
Publisher
Proceedings of the National Academy of Sciences
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