Molecular Coevolutionary Drive

Abstract Most aspects of the molecular biology of cells involve tightly coordinated intermolecular interactions requiring specific recognition at the nucleotide and/or amino-acid levels. This has led to long-standing interest in the degree to which constraints on interacting molecules result in conserved vs. accelerated rates of sequence evolution, with arguments commonly being made that molecular coevolution can proceed at rates exceeding the neutral expectation. Here, a fairly general model is introduced to evaluate the degree to which the rate of evolution at functionally interacting sites is influenced by effective population sizes ( N e ), mutation rates, strength of selection, and the magnitude of recombination between sites. This theory is of particular relevance to matters associated with interactions between organelle- and nuclear-encoded proteins, as the two genomic environments often exhibit dramatic differences in the power of mutation and drift. Although genes within low N e environments can drive the rate of evolution of partner genes experiencing higher N e , rates exceeding the neutral expectation require that the former also have an elevated mutation rate. Testable predictions, some counterintuitive, are presented on how patterns of coevolutionary rates should depend on the relative intensities of drift, selection, and mutation. Significance Statement A wide variety of features at the cellular level involve precise interactions between participating molecular partners, thereby requiring coordinated co-evolutionary changes within lineages. The same is true for ecological interactions between species. Although there has been much speculation on how such constraints might drive molecular evolutionary rates beyond the neutral expectation, there has been little formal evolutionary theory to evaluate the generality of such claims. Here, a general framework is developed for ascertaining how rates of sequence evolution depend on the population-genetic environments of both interacting partner molecules. Although the features of one site can indeed drive the evolution of the other, only under restrictive conditions does this process push rates beyond the neutral expectation.