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.

Material for the study "Influence of genetic recombination on protein folding stability" by Roberto Del Amparo, Laura Rodriguez-Moure, Ugo Bastolla and Miguel Arenas. The directory "DataSimulatedWithSCSmodels" includes for every protein family a subdirectory with the protein data evolved under SCS models with mutation and recombination events. It also includes the corresponding predicted protein folding stability. In addition, it includes the applied tools, including the program Prot_evol and several scripts. The directory "DataSimulatedWithEmpiricalmodels" includes for every protein family a subdirectory with the data used for every figure. This data was simulated under the empirical models with recombination events with the program "ProteinEvolver" (freely available from https://github.com/MiguelArenas/proteinevolver/). The data is organized by figures and for the corresponding cases it specifies the population substitution rates (theta) and recombination rates (rho) used for the simulations. Please do not hesitate to contact us (marenas@uvigo.es) for any question.