Natural Selection and Mutation Rates in Mammals

Rates of fixation of amino acid substitutions were calculated for 13 amino acid positions of fibrinopeptides A and B. These positions were selected because they had sustained fixation of nonconservative amino acid substitutions and had sustained more fixations (6 or more) than those positions at which all substitutions fixed were conservative. We have used the average of these rates to estimate the average rate at which mutations would be fixed if all were selectively neutral. The percentage of mutations eliminated by selection after they have reached frequencies high enough for selection to act on them was estimated by comparing the potential rate at which mutations would be fixed if selectively neutral with an observed rate of fixation. It is estimated that at least 79% of mutations that become frequent enough to be affected by natural selection are eliminated. We assume that the probability of a mutation reaching a frequency at which selection affects it is independent of whether it is selectively advantageous, neutral, or deleterious. We conclude, therefore, that at least 79% of all mutations are deleterious. An estimate of the mutation rate can be derived from these data if all mutations at the 13 positions considered are selectively neutral. When allowances are made both for the number of cell divisions along the germ line leading from zygote to gamete and for the number of nucleotides that may be substituted, the estimated mutation rate is within an order of magnitude of mutation rates derived in other ways.