Quantifying antagonistic epistasis in a multifunctional RNA secondary structure of the Rous sarcoma virus

Recent studies have suggested that antagonistic epistasis (i.e. mutations having smaller effects in combination than alone) may be common among RNA viruses, in contrast to other biological systems. Here, by re-analysing previously published data from a random viral library, selection and epistasis coefficients were estimated in the U5-IR stem and loop of the Rous sarcoma virus, a region that adopts a conserved secondary structure and is involved in various essential steps of viral infection. The estimated mutational fitness effects are extremely high and genetic interactions are antagonistic on average. This pattern might be representative of RNA virus genomes, which show high compaction and frequent secondary structures. The implications for RNA virus adaptability are explored.