Engineered Genetic Redundancy Relaxes Selective Constraints upon Endogenous Genes in Viral RNA Genomes

Abstract

1Genetic redundancy, understood as the functional overlap of different genes, is a double-edge sword. At the one side, it is thought to serve as a robustness mechanism that buffers the deleterious effect of mutations hitting one of the redundant copies, thus resulting in pseudogenization. At the other side, it is considered as a source of genetic and functional innovation. In any case, genetically redundant genes are expected to show an acceleration in the rate of molecular evolution. Here we tackle the role of genetic redundancy in viral RNA genomes. To this end, we have evaluated the rates of compensatory evolution for deleterious mutations affecting an essential function, the suppression of RNA silencing plant defense, of tobacco etch potyvirus (TEV). TEV genotypes containing deleterious mutations in presence/absence of engineered genetic redundancy were evolved and the pattern of fitness and virulence recovery evaluated. Genetically redundant genotypes suffered less from the effect of deleterious mutations and showed relatively minor changes in fitness and virulence. By contrast, non-genetically redundant genotypes had very low fitness and virulence at the beginning of the evolution experiment that were fully recovered by the end. At the molecular level, the outcome depended on the combination of the actual mutations being compensated and the presence/absence of genetic redundancy. Reversions to wild-type alleles were the norm in the non-redundant genotypes while redundant ones either did not fix any mutation at all or showed a higher nonsynonymous mutational load.