Abstract
Deleterious mutations can have a strong influence on the outcome of evolution. The nature of this influence depends on how mutations combine together to affect fitness. "Negative epistasis" occurs when a new deleterious mutation causes the greatest loss in fitness in a genome that already contains many deleterious mutations. Negative epistasis is a key ingredient for some of the leading hypotheses regarding the evolution of recombination, the evolution of sex, and a variety of other phenomena. In general, laboratory studies have not supported the idea that negative epistasis is ubiquitous, and this has led to doubts about its importance in biological evolution. Here, we show that these experimental results may be misleading, because negative epistasis can produce evolutionary advantages for sex and recombination while simultaneously being almost impossible to detect using current experimental methods. Under asexual reproduction, such hidden epistasis influences evolutionary outcomes only if the fittest individuals are present in substantial numbers, while also forming a very small proportion of the population as a whole. This implies that our results for asexuals will apply only for very large populations, and also limits the extent of the fitness benefits that hidden epistasis can provide. Despite these caveats, our results show that the fitness consequences of sex and recombination cannot always be inferred from observable epistasis alone.