A Recent Global Selective Sweep on the age-1 Phosphatidylinositol 3-OH Kinase Regulator of the Insulin-Like Signaling Pathway Within Caenorhabditis remanei

Abstract

Abstract The discovery that genetic pathways can be manipulated to extend lifespan has revolutionized our understanding of aging, yet their function within natural populations remains poorly characterized. In particular, evolutionary theories of aging predict tradeoffs in resource investment toward somatic maintenance vs. reproductive output that should impose strong natural selection on genetic components that influence this balance. To explore such selective pressure at the molecular level, we examine population genetic variation in the insulin-like signaling pathway of the nematode Caenorhabditis remanei. We document a recent global selective sweep on the phosphoinositide-3-kinase pathway regulator, age-1, the first life-extension gene to have been identified. In particular, we find that age-1 has 5−20 times less genetic variation than any other insulin-like signaling pathway components and that evolutionary signatures of selection center on the age-1 locus within its genomic environment. These results demonstrate that critical components of aging-related pathways can be subject to shifting patterns of strong selection, as predicted by theory. This highly polymorphic outcrossing species offers high-resolution, population-level analyses of molecular variation as a complement to functional genetic studies within the self-reproducing C. elegans model system.