Getting There First: An Evolutionary Rate Advantage for Adaptive Loss-of-Function Mutations

Over the course of evolution organisms have adapted to their environments by mutating to gain new functions or to lose pre-existing ones. Because adaptation can occur by either of these modes, it is of basic interest to assess under what, if any, evolutionary circumstances one of them may predominate. Since mutation occurs at the molecular level, one must look there to discern if an adaptation involves gainor loss-of-function. Here I present a simple, deterministic model for the occurrence and spread of adaptive gain-of-function versus loss-of-function mutations, and compare the results to laboratory evolution experiments and studies of evolution in nature. The results demonstrate that loss-of-function mutations generally have an intrinsic evolutionary rate advantage over gain-offunction mutations, but that the advantage depends radically on population size, ratio of selection coefficients of competing adaptive mutations, and ratio of the mutation rates to the adaptive states.