Adaptive introgression of the beta-globin cluster in two Andean waterfowl.

Introgression of beneficial alleles has emerged as an important avenue for genetic adaptation in both plant and animal populations. In vertebrates, adaptation to hypoxic high-altitude environments involves the coordination of multiple molecular and cellular mechanisms, including selection on the hypoxia-inducible factor (HIF) pathway and the blood-O2 transport protein hemoglobin (Hb). In two Andean duck species, a striking DNA sequence similarity reflecting identity by descent is present across the ~20 kb ß-globin cluster including both embryonic (HBE) and adult (HBB) paralogs, though it was yet untested whether this is due to independent parallel evolution or adaptive introgression. In this study, we find that identical amino acid substitutions in the ß-globin cluster that increase Hb-O2 affinity have likely resulted from historical interbreeding between high-altitude populations of two different distantly-related species. We examined the direction of introgression and discovered that the species with a deeper mtDNA divergence that colonized high altitude earlier in history (Anas flavirostris) transferred adaptive genetic variation to the species with a shallower divergence (A. georgica) that likely colonized high altitude more recently possibly following a range shift into a novel environment. As a consequence, the species that received these ß-globin variants through hybridization might have adapted to hypoxic conditions in the high-altitude environment more quickly through acquiring beneficial alleles from the standing, hybrid-origin variation, leading to faster evolution.

Gene flow in the face of countervailing selection: adaptation to high-altitude hypoxia in the betaA hemoglobin subunit of yellow-billed pintails in the Andes.

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.

Signatures of high-altitude adaptation in the major hemoglobin of five species of andean dabbling ducks.

Hypoxia is one of the most important factors affecting survival at high altitude, and the major hemoglobin protein is a likely target of selection. We compared population genetic structure in the alphaA and betaA hemoglobin subunits (HBA2 and HBB) of five paired lowland and highland populations of Andean dabbling ducks to unlinked reference loci. In the hemoglobin genes, parallel amino acid replacements were overrepresented in highland lineages, and one to five derived substitutions occurred at external solvent-accessible positions on the alpha and beta subunits, at alpha(1)beta(1) intersubunit contacts, or in close proximity to inositolpentaphosphate (IPP) binding sites. Coalescent analyses incorporating the stochasticity of drift and mutation indicated that hemoglobin alleles were less likely to be transferred between highland and lowland populations than unlinked alleles at five other loci. Amino acid replacements that were overrepresented in the highlands were rarely found within lowland populations, suggesting that alleles segregating at high frequency in the highlands may be maladaptive in the lowlands and vice versa. Most highland populations are probably nonmigratory and locally adapted to the Altiplano, but gene flow for several species may be sufficiently high to retard divergence at unlinked loci. Heterozygosity was elevated in the alphaA or betaA subunits of highland populations exhibiting high gene flow between the southern lowlands and the highlands and in highland species that disperse seasonally downslope to midelevation environments from the central Andean plateau. However, elevated heterozygosity occurred more frequently in the alphaA subunit but not simultaneously in both subunits, suggesting that selection may be more constrained by epistasis in the betaA subunit. Concordant patterns among multiple species with different evolutionary histories and depths of historical divergence and gene flow suggest that the major hemoglobin genes of these five dabbling duck species have evolved adaptively in response to high-altitude hypoxia in the Andes.