Shifts in mutation spectra enhance access to beneficial mutations

Abstract

ABSTRACTBiased mutation spectra are pervasive, with widely varying direction and magnitude of mutational biases that influence genome evolution and adaptation. Why are unbiased spectra rare, and how do such diverse biases evolve? Our experiments show that changing the mutation spectrum allows populations to sample previously under-sampled mutational space, including new beneficial mutations. The resulting shift in the distribution of fitness effects is advantageous: beneficial mutation supply and beneficial pleiotropy both increase, and deleterious load reduces. More broadly, adaptive walk simulations indicate that the evolution of a mutational bias in an unbiased ancestor is selectively neutral; but reversing the direction of a long-term bias is always selectively favoured. Indeed, spectrum changes in the bacterial phylogeny occur frequently, typically involving reversals of ancestral bias. Thus, shifts in mutation spectra may evolve under selection, and can directly alter the outcome of adaptive evolution by facilitating access to beneficial mutations.SIGNIFICANCE STATEMENTMutations are important because they provide raw material for evolution. Some types of mutations occur more often than others, but the direction and degree of such mutational biases varies. How do mutational biases evolve, and do they influence evolution? We experimentally measured the immediate effects of changing the mutation bias of E. coli, and used simulations to test the long-term effects. Altering mutational bias is beneficial whenever the new bias increases sampling of mutational classes that were previously under-sampled. We also show that historically, bacteria have often experienced such beneficial bias switches. Our work demonstrates the importance of mutational biases in evolution. By allowing exploration of new mutational space, altered mutation biases could drive rapid adaptation even in constant environments.