Abstract
Adaptive mutations play an important role in molecular evolution. However, the frequency and nature of these mutations at the intramolecular level are poorly understood. To address this, we analyzed the impact of protein architecture on the rate of adaptive substitutions, aiming to understand how protein biophysics influences fitness and adaptation. Using Drosophila melanogaster and Arabidopsis thaliana population genomics data, we fitted models of distribution of fitness effects and estimated the rate of adaptive amino-acid substitutions both at the protein and amino-acid residue level. We performed a comprehensive analysis covering genome, gene, and protein structure, by exploring a multitude of factors with a plausible impact on the rate of adaptive evolution, such as intron number, protein length, secondary structure, relative solvent accessibility, intrinsic protein disorder, chaperone affinity, gene expression, protein function, and protein-protein interactions. We found that the relative solvent accessibility is a major determinant of adaptive evolution, with most adaptive mutations occurring at the surface of proteins. Moreover, we observe that the rate of adaptive substitutions differs between protein functional classes, with genes encoding for protein biosynthesis and degradation signaling exhibiting the fastest rates of protein adaptation. Overall, our results suggest that adaptive evolution in proteins is mainly driven by intermolecular interactions, with host-pathogen coevolution likely playing a major role.