Primate hemoglobins: Some sequences and some proposals concerning the character of evolution and mutation

During a multipurpose survey we examined electrophoretic mobilities of major (A, i.e., ₂₂) and minor (A₂, i.e., ₂₂) adult hemoglobins from populations of nine primate genera representing a total of 440 New World monkeys and apes. Sequences of hemoglobin chains were inferred from differences in amino acid composition between homologous tryptic peptides supplemented by detailed placement of more than 270 residues. Beta sequences were thus analyzed in five genera (Aotus, Ateles, Hylobates, Saimiri, and Saguinus) and sequences in seven (foregoing plus Gorilla and Pan). In most genera, sequences from several individuals, often from several species, were delineated. Fifteen kinds of intraspecies mutants were detected; 10 of these were precisely characterized. Five of the 15 mutants form electrophoretically detected genetic polymorphisms of ; none such occur in . Six electrophoretically detected mutants, four in and two in , are uncommon. One of these represents the complete absence of minor component. Three kinds of variants, two in and one in , are electrophoretically neutral and chance findings during sequence analysis of the equivalent of 38 allele products. Two of the neutral variants are not especially common; one may have polymorphic frequency. Several general conclusions stem from these and supplementary findings. First, comparisons of sequences suggest that and genes in all primates either arose from a single event in a common ancestor or from two approximately coincident events. Either assumption allows reconstruction of a reasonably accurate archetype sequence that is effectively common to all descendants. Second, there is a pancellular quantitative disproportion between major and minor hemoglobins ranging from 16:1 to 220:1 in species studied. Delta is consequently presumed to be functionally and adaptively less vital than . When these premises are adopted, is expected to be relatively invisible to natural selection, and, where darwinism is the principal arbiter of evolution and polymorphism, is expected to show fewer fixed changes and fewer genetic polymorphisms than . The opposite is observed. Delta exhibits as many or more changes from archetype than . This finding and the comparative abundance of polymorphism are attributed to nonadaptive factors which are thus considered the source of much evolutionary change. Third, particular sequence positions in various species are the site of recurrent mutations in both and . One such area is occupied by the majority of genetic polymorphisms found in man and other primates. The overall distribution of mutations arising in evolution is remarkably nonrandom in , , and a pool of both. These results are quite unlike most other observations in higher organisms. The sources of such nonrandomness are either selection and/or differential mutability. We rely on our prior assumption of relative selective invisibility for and, in part, ascribe the nonrandom distribution of changes to microzones of enhanced mutability. Fourth, the six uncommon electrophoretically detected mutants provide an estimate of heterozygosity (1/73) at hemoglobin loci that is tenfold greater than observed in man. Fifth, the unprecedented chance detection of three kinds of electrophoretically neutral intraspecies mutants among the equivalent of 38 characterized allele products suggests that neutral changes are as common as electrostatically active ones and at least tenfold more common than expected in extrapolation from human variant surveys. Sixth, analyses from three kinds of gibbon (Hylobates) hemoglobin suggest that one of these is a potentially unchanged relict of the ancient archetype and, further, indicate a degree of homozygous diversity within a species that nearly equals the difference between gibbon and man.This investigation received support from grants to S.H.B., HD-02508-04 and K3-GM-6308-03, from the National Institutes of Health.