Molecular adaptation reflects taxon-specific mutational biases

A fundamental question in molecular evolution is the extent to which patterns of adaptive change are shaped by mutational biases that make some variants more likely than others to arise. Past studies provide support for important effects of mutation bias on adaptive change, but leave open the empirical question of how strongly and how broadly evolutionary patterns depend on taxon-specific mutational tendencies. To characterize this effect quantitatively, we aggregated frequency spectra of adaptive amino acid changes from 14 species, comprising over 5000 total adaptive events, primarily from adaptive laboratory evolution studies. We then paired each species-specific spectrum of adaptive changes with independent measurements of the mutation spectrum of that same species. Across the 14 species, we find considerable heterogeneity in the relative frequencies of the six possible types of single-nucleotide changes, for both the mutational and adaptive spectra. Comparing these spectra across species, we find that, for any given mutation type, the stronger the bias toward or against that type in a species mutation spectrum, the more enriched or depleted it tends to be in that species adaptive spectrum. We conclude that, for the adaptation of proteins via amino acid changes, taxon-specific evolutionary preferences are strongly responsive to taxon-specific mutational preferences over their observed range. Significance statementThe rates at which different types of mutation occur vary widely, both for different types of mutations within a single species and across species. Historically, a strong concordance between patterns of sequence evolution and mutational biases was used to support the thesis that most sequence evolution is caused by variants that do not affect fitness. However, more recent evidence shows that mutational biases can also influence adaptive evolution. Using data from 14 species, we find a strong relationship between the rate at which different kinds of nucleotide mutations emerge and their frequency among adaptive amino acid changes during protein evolution. These results suggest that processes that bias the production of variation may have a strong impact even during adaptive evolution.