Evolutionary journey of the retroviral restriction gene <i>Fv1</i>.

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, <i>Fv1</i>, is now understood to exhibit a degree of control across multiple retroviral genera and is highly diverse within <i>Mus</i> To better understand the age and evolutionary history of <i>Fv1</i>, a comprehensive survey of the Muroidea was conducted, allowing the progenitor integration to be dated to ∼45 million years. Intact coding potential is visible beyond <i>Mus</i>, and sequence analysis reveals strong signatures of positive selection also within field mice, <i>Apodemus</i><i>Fv1</i>'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 of <i>Fv1</i> adapt 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.