Data files associated with: Evolution of the mutation spectrum across a mammalian phylogeny

Although evolutionary biologists have long theorized that variation in DNA
repair efficacy might explain some of the diversity of lifespan and cancer
incidence across species, we have little data on the variability of normal
germline mutagenesis outside of humans. Here, we shed light on the
spectrum and etiology of mutagenesis across mammals by quantifying
mutational sequence context biases using polymorphism data from thirteen
species of mice, apes, bears, wolves, and cetaceans. After normalizing the
mutation spectrum for reference genome accessibility and k-mer content, we
use the Mantel test to deduce that mutation spectrum divergence is highly
correlated with genetic divergence between species, whereas life history
traits like reproductive age are weaker predictors of mutation spectrum
divergence. Potential bioinformatic confounders are only weakly related to
a small set of mutation spectrum features. We find that clocklike
mutational signatures previously inferred from human cancers cannot
explain the phylogenetic signal exhibited by the mammalian mutation
spectrum, despite the ability of these clocklike signatures to fit each
species’ 3-mer spectrum with high cosine similarity. In contrast, parental
aging signatures inferred from human de novo mutation data appear to
explain much of the mutation spectrum’s phylogenetic signal when fit to
non-context-dependent mutation spectrum data in combination with a novel
mutational signature. We posit that future models purporting to explain
the etiology of mammalian mutagenesis need to capture the fact that more
closely related species have more similar mutation spectra; a model that
fits each marginal spectrum with high cosine similarity is not guaranteed
to capture this hierarchy of mutation spectrum variation among species.