Mutation bias shapes the spectrum of adaptive substitutions

Significance How do mutational biases influence the process of adaptation? A common assumption is that selection alone determines the course of adaptation from abundant preexisting variation. Yet, theoretical work shows broad conditions under which the mutation rate to a given type of variant strongly influences its probability of contributing to adaptation. Here we introduce a statistical approach to analyzing how mutation shapes protein sequence adaptation. Using large datasets from three different species, we show that the mutation spectrum has a proportional influence on the types of changes fixed in adaptation. We also show via computer simulations that a variety of factors can influence how closely the spectrum of adaptive substitutions reflects the spectrum of variants introduced by mutation.