Protein biochemistry shapes the fate of duplicated genes

Gene duplication impacts genome evolution and cell biology in many ways. A major determinant of the outcome of gene duplication is the probability of long-term retention of the new gene copies. We have limited knowledge of how gene properties influence this probability. Using deep mutational scanning, we are exploring the fitness landscape of proteins following gene duplication to elucidate how molecular interactions define the impact of mutations on the fate of gene duplicates. We focus on the duplication of homomeric proteins, which, following gene duplication, form heteromeric complexes composed of duplicated proteins. Our experimental and theoretical results show that homodimerization can extend the retention of gene duplicates through various mechanisms, which can be explained by the impact of mutations on protein stability and structure. Our results demonstrate how protein biochemistry influences the long-term fate of gene duplicates.