New evolutionary dynamics emerge from phenotypic noise*

Although population genetics in the diffusion limit has been well-studied for decades, evolutionary dynamics when the genotype-phenotype map is noisy—a reality for most evolving biological systems—remains unexplored. Here, we introduce a theory for evolutionary dynamics under phenotypic uncertainty and discover several new phenomena, including a new dependence of the dynamics on absolute fitness even at fixed population size. Next, we show our theory predicts "phenotype buoying," the ability of a low-fitness phenotype to exist at surprisingly high frequencies when carried by a high-fitness phenotype via a low genotype-to-phenotype mapping probability. We also discover that phenotype uncertainty creates "phenotype bridges" that accelerate fitness valley crossing. To validate our theory, we develop a new evolution simulation algorithm similar to the Wright-Fisher model, except ours is capable of capturing probabilistic genotype-phenotype mapping. Promisingly, our new diffusion limit of population genetics may explain the empirically observed importance of phenotype noise in chemotherapy resistant cancers.