Selection intensity against deleterious mutations in RNA secondary structures and rate of compensatory nucleotide substitutions

A two-locus model of reversible mutations with compensatory fitness interac tions is presented; single mutations are assumed to be deleterious but neut ral in appropriate combinations. The expectation of the time of compensator , nucleotide substitutions is calculated analytically for the case of fight linkage between sites. It is shown that selection increases the substituti on time dramatically Mien selection intensity Ns > 1, where N is the diploi d population size and s the selection coefficient. Computer simulations dem onstrate that recombination increases the substitution time, but the effect of recombination is small when selection is weak. The amount of linkage di sequilibrium generated in the process of compensatory substitution is also investigated. It is shown that significant linkage disequilibrium is expect ed to be rare in natural populations. The model is applied to the mRNA seco ndary, structure of the bicoid 3 ' untranslated region of Drosophila. It is concluded that average selection intensity,Ys against single deleterious m utations is not likely to be much larger than 1.