Neutral evolution of mutational robustness

We introduce and analyze a general model of a population evolving over a network of selectively neutral genotypes. We show that the population’s limit distribution on the neutral network is solely determined by the network topology and given by the principal eigenvector of the network’s adjacency matrix. Moreover, the average number of neutral mutant neighbors per individual is given by the matrix spectral radius. These results quantify the extent to which populations evolve mutational robustness—the insensitivity of the phenotype to mutations—and thus reduce genetic load. Because the average neutrality is independent of evolutionary parameters—such as mutation rate, population size, and selective advantage—one can infer global statistics of neutral network topology by using simple population data available from in vitro or in vivo evolution. Populations evolving on neutral networks of RNA secondary structures show excellent agreement with our theoretical predictions.