Search

Theory predicts that parallel evolution should be common when the number of beneficial mutations is limited by selective constraints on protein structure. However, confirmation is scarce in natural populations. Here we studied the major haemoglobin genes of eight Andean duck lineages and compared them to 115 other waterfowl species, including the bar-headed goose (Anser indicus) and Abyssinian blue-winged goose (Cyanochen cyanopterus), two additional species living at high altitude. One to five amino acid replacements were significantly overrepresented or derived in each highland population, and parallel substitutions were more common than in simulated sequences evolved under a neutral model. Two substitutions evolved in parallel in the alpha A subunit of two (Ala-alpha 8) and five (Thr-alpha 77) taxa, and five identical beta A subunit substitutions were observed in two (Ser-beta 4, Glu-beta 94, Met-beta 133) or three (Ser-beta 13, Ser-beta 116) taxa. Substitutions at adjacent sites within the same functional protein region were also observed. Five such replacements were in exterior, solvent-accessible positions on the A helix and AB corner of the alpha A subunit. Five others were in close proximity to inositolpentaphosphate binding sites, and two pairs of independent replacements occurred at two different alpha(1)beta(1) intersubunit contacts. More than half of the substitutions in highland lineages resulted in the acquisition of serine or threonine (18 gains vs. 2 losses), both of which possess a hydroxyl group that can hydrogen bond to a variety of polar substrates. The patterns of parallel evolution observed in these waterfowl suggest that adaptation to high-altitude hypoxia has resulted from selection on unique but overlapping sets of one to five amino acid substitutions in each lineage.

When populations become locally adapted to contrasting environments, alleles that have high fitness in only one environment may be quickly eliminated in populations adapted to other environments, such that gene flow is partly restricted. The stronger the selection, the more rapidly immigrant alleles of lower fitness will be eliminated from the population. However, gene flow may continue to occur at unlinked loci, and adaptive divergence can proceed in the face of countervailing gene flow if selection is strong relative to migration (s > m). We studied the population genetics of the major hemoglobin genes in yellow-billed pintails (Anas georgica) experiencing contrasting partial pressures of oxygen in the Andes of South America. High gene flow and weak population subdivision were evident at seven putatively neutral loci in different chromosomal linkage groups. In contrast, amino acid replacements (Ser-beta13, Ser-beta116, and Met-beta133) in the betaA hemoglobin subunit segregated by elevation between lowland and highland populations with significantly elevated F(ST). Migration rates for the betaA subunit alleles were approximately 17-24 times smaller than for five unlinked reference loci, the alphaA hemoglobin subunit (which lacks amino acid replacements) and the mitochondrial DNA control region. The betaA subunit alleles of yellow-billed pintails were half as likely to be transferred downslope, from the highlands to the lowlands, than in the opposite direction upslope. We hypothesize that migration between the lowlands and highlands is restricted by local adaptation, and the betaA hemoglobin subunit is a likely target of selection related to high-altitude hypoxia; however, gene flow may be sufficiently high to retard divergence at most unlinked loci. Individuals homozygous for lowland alleles may have relatively little difficulty dispersing to the highlands initially but may experience long-term fitness reduction. Individuals homozygous for highland genotypes, in contrast, would be predicted to have difficulty dispersing to the lowlands if their hemoglobin alleles confer high oxygen affinity, predicted to result in chronic erythrocytosis at low elevation. Heterozygous individuals may have a dispersal advantage if their hemoglobin has a wider range of function due to the presence of multiple protein isoforms with a mixture of different oxygen affinities.