Patterns of epistasis in RNA viruses: a review of the evidence from vaccine design.

Journal of Evolutionary Biology 16:1223-1235.
Year of Publication: 
Burch, C.L., P.E. Turner, K. Hanley.

Epistasis results when the fitness effects of a mutation change depending on the presence or absence of other mutations in the genome. The predictions of many influential evolutionary hypotheses are determined by the existence and form of epistasis. One rich source of data on the interactions among deleterious utations that has gone untapped by evolutionary biologists is the literature on the design of live, attenuated vaccine viruses. Rational vaccine design depends upon the measurement of individual and combined effects of deleterious mutations. In the current study we have reviewed data from 29 vaccine-oriented studies using 14 different RNA viruses. Our analyses indicate: (1) that no consistent tendency toward a particular form of epistasis exists across RNA viruses and (2) that significant interactions among groups of mutations within individual viruses occur but are not common. RNA viruses are significant pathogens of human disease, as well as tractable model systems for evolutionary studies - we discuss the relevance of our findings in both contexts.