Influence of genetic recombination on protein folding stability

Genetic recombination is a common evolutionary mechanism that produces molecular diversity. However, its consequences on protein folding stability have not attracted the same attention as in the case of point mutations. Here, we studied the effects of homologous recombination on the computationally predicted protein folding stability for several protein families, finding less detrimental effects than we would have expected. Despite recombination can affect multiple protein sites, we found that the fraction of recombined proteins that are eliminated by negative selection because of insufficient folding stability is not significantly larger than the corresponding fraction of proteins produced by mutation events. Indeed, despite recombination disrupts epistatic interactions, the mean stability of recombinant proteins is not lower than that of their parents. On the other hand, the difference of stability between recombined proteins is amplified with respect to the parents, promoting phenotypic diversity. As a result, at least one third of recombined proteins present stability between those of their parents, and a substantial fraction have higher or lower stability than those of both parents. As expected, we found that parents with similar sequences tend to produce descendants with stability close to that of the parents. Finally, the simulation of protein evolution under mutation and recombination events with empirical substitution models, which ignore constraints on protein folding stability, showed that recombination favors the decrease of folding stability of the simulated proteins, supporting the view that considering substitution models and recombination with constraints on protein folding stability is recommended for evolutionary inferences.