Massively parallel experimental interrogation of natural variants in ancient signaling pathways reveals both purifying selection and local adaptation.

ABSTRACT: The nature of standing genetic variation remains a central debate in population genetics, with differing perspectives on whether common variants are mostly neutral or have functional effects. We address this question by directly mapping the fitness effects of over 9,000 natural variants in the Ras/PKA and TOR/Sch9 pathways-key regulators of cell proliferation in eukaryotes-across four conditions in Saccharomyces cerevisiae. While many variants are neutral in our assay, on the order of 3,500 exhibited significant fitness effects. These non-neutral variants tend to be missense and affect conserved, more densely packed, and less solvent-exposed protein regions. They are also typically younger, occur at lower frequencies, and more often found in heterozygous states, suggesting they are

SUBMITTER: Aguilar-Rodriguez J 

PROVIDER: S-EPMC11565963 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature