Effects of gene duplication, epistasis, recombination and gene conversion on the fixation time of compensatory...

Gene duplication is one of the major mechanisms of molecular evolution. Gene duplication enables copies of a gene to accumulate mutations through functional redundancy. If a gene encodes a specific protein that interacts with other proteins, RNA, or DNA, the relaxation of selective constraints caused by gene duplication might contribute to the fixation of compensatory mutations that occur at the interacting sites. In this study, we investigate the effect of gene duplication, epistasis among the duplicated copies and gene conversion on the fixation time of compensatory mutations by extending the original model of compensatory evolution proposed by Kimura in 1985. Our simulation results reveal that the time to fixation of compensatory mutations can be decreased remarkably by gene duplication if one of the duplicated loci can completely mask the deleterious effects of a mutation that occurs at the other locus. Conversely, the fixation time can be increased by gene duplication if such functional compensation is weak. We also show that the combination of the degree of functional compensation and the rate of gene conversion between duplicate loci have contrasting effects on the time to fixation of compensatory mutations.