Estimating Time Depth With Mutation Rates Is Intrinsically Complex
Early estimates of the time depth at which genetic clades emerged were based upon a fixed molecular clock model that turns out to not reflect reality. Mutation does happen at predictable rates, but a workable model is more complex. Not all kinds of genetic mutations take place at the same rate.
Recent studies of hominoid variation have shown that mutation rates and spectra can evolve rapidly, contradicting the fixed molecular clock model. The relative mutation rates of three-base-pair motifs differ significantly among great ape species, suggesting the action of unknown modifiers of DNA replication fidelity. To illuminate the footprints of these hypothetical mutators, we measured mutation spectra of several functional compartments (such as late-replicating regions) that are likely targeted by localized mutational processes. Using genetic diversity from 88 great apes, we find that compartment-specific mutational signatures appear largely conserved between species. These signatures layer with species-specific signatures to create rich mutational portraits: for example, late-replicating regions in gorillas contain an identifiable mixture of a replication timing signature and a gorilla-specific signature. Our results suggest that cis-acting mutational modifiers are highly conserved between species and transacting modifiers are driving rapid mutation spectrum evolution.
The authors also deserve credit for clearly packing the key ideas of their paper into the title.