Adaptive value of high mutation rates of RNA viruses: separating causes from consequences.

Abstract

As a consequence of the lack of proofreading activity of RNA virus polymerases, new viral genetic variants are constantly created. RNA viruses readily adapt to changing environmental conditions. Therefore, the high mutation rate of RNA viruses compared with DNA organisms is responsible for their enormous adaptive capacity. The above syllogism, with some variation, is deeply rooted in the thinking of many virologists: RNA viruses mutate at the maximum error rate compatible with maintaining the integrity of genetic information (i.e., the error threshold) because this would allow them to quickly find the beneficial mutations needed for adaptation (12, 14, 23, 32). It is an unquestionable fact that RNA virus populations exist as swarms of mutant genotypes (13). Such enormous variability is an unavoidable consequence of the lack of exonuclease proofreading activity of the virus-encoded RNA polymerases (44) with, in some cases, the added contribution of recombination (20, 29, 33). However, the argument that the more mutations are generated, the faster adaptation proceeds is flawed because it ignores the fact that the vast majority of mutations are deleterious, hence hindering adaptation, as shown by recent theoretical developments (25, 34). Therefore, the adaptive value of the RNA virus extreme mutation rate has to be carefully reconsidered, and new alternative explanations, beyond a purely mechanistic level, should be taken into consideration.