Genotype network intersections promote evolutionary innovation

Evolutionary innovations are qualitatively novel traits that emerge through evolution and increase biodiversity. The genetic mechanisms that lead to innovation remain poorly understood. A systems view of innovation requires the analysis of genotype networks - the vast networks of genetic variants that produce the same phenotype. Innovations can occur at the intersection of two different genotype networks. Here, we use high-throughput sequencing to study the fitness landscape at the intersection of the genotype networks of two catalytic RNA molecules (ribozymes). We determined the ability of numerous neighboring RNA sequences to catalyze two different chemical reactions. We find extensive functional overlap, and over half the genotypes can catalyze both functions to some extent. We demonstrate through evolutionary simulations that these numerous points of intersection facilitate the discovery of a new function. Our study reveals the properties of a fitness landscape where genotype networks intersect, and the consequences for evolutionary innovations.