Presentation: Covariation of Mutation Spectra Across the Genome and the Ape Phylogeny
Speaker: Kelley Harris, PhD, Assistant Professor of Genome Sciences, University of Washington
Abstract: Although the germline mutation rate is classically regarded as a fixed parameter of the evolutionary process, recent studies of human and ape genetic variation have shown that the mutation rate and spectrum can evolve rapidly. The relative mutation rates of different three-base-pair genomic motifs differ significantly among great ape species, suggesting the recent fixation of unknown genetic or environmental modifiers of DNA replication fidelity. To shed further light on the footprint of these mutators, we measured the relative mutabilities of all three-base-pair motifs in functional compartments of the genome (such as late-replicating regions and endogenous retroviral elements) that we expect to be targeted by known mutational processes. Using genetic diversity data from 88 great apes, we measured the covariation of mutational spectra between compartments and species, finding evidence of compartment-specific mutational processes that are largely conserved across the ape phylogeny. These compartment-specific signatures layer with species-specific signatures to create rich mutational portraits: for example, late replicating regions in gorillas contain an identifiable mixture of a gorilla-specific signature and a signature indicative of late replication timing that is conserved across the entire great ape lineage. In addition, we identify a mutation signature enriched in endogenous retroviruses that we hypothesize is due to hydroxymethylation of retrovirus-derived DNA. Our results suggest that rapidly evolving mutation rate modifiers tend to act broadly in trans across the whole genome, whereas cis regulators of mutation in specific genomic compartments are highly conserved between species.
This is joint work with Michael Goldberg.