How Sequence Context-Dependent Mutability Drives Mutation Rate Variation in the Genome.

ABSTRACT: The rate of mutations varies >100-fold across the genome, altering the rate of evolution, and susceptibility to genetic diseases. The strongest predictor of mutation rate is the sequence itself, varying 75-fold between trinucleotides. The fact that DNA sequence drives its own mutation rate raises a simple but important prediction; highly mutable sequences will mutate more frequently and eliminate themselves in favor of sequences with lower mutability, leading to a lower equilibrium mutation rate. However, purifying selection constrains changes in mutable sequences, causing higher rates of mutation. We conduct a simulation using real human mutation data to test if 1) DNA evolves to a low equilibrium mutation rate and 2) purifying selection causes a higher equilibrium mutation rate in the ge

SUBMITTER: Oman M 

PROVIDER: S-EPMC8920511 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature