PRINCIPAL INVESTIGATORS: Kevin G. McCracken and Jay F. Storz
PROJECT NUMBER: IOS-0949439 and IOS-0949931
Conclusive inferences about adaptive evolution ultimately require an understanding of mechanism. Patterns of DNA sequence variation can provide suggestive evidence for a history of natural selection on a particular gene or set of genes, but these indirect inferences should serve as a stepping-off point for experiments to identify specific mechanisms of adaptation. Accordingly, the purpose of the proposed research project is to follow up a comprehensive survey of DNA sequence variation in the hemoglobin genes of Andean waterfowl to gain insight into the functional (and possibly, adaptive) significance of the observed amino acid polymorphisms. The goal of this project is to determine whether parallel amino acid substitutions in highland populations of eight species of Andean ducks have produced similar functional changes in hemoglobin-O2 affinity. This project will integrate DNA sequence data with functional experiments to identify possible mechanisms of adaptation, and will determine whether the same or different mechanisms underlie adaptation to high-altitude hypoxia in eight replicate lineages that independently colonized the high Andes. The research will provide information about the number and types of amino acid substitutions that are involved in potentially adaptive traits, and will also provide a point of contrast for studies of humans inhabiting high-altitude regions. The work will assemble a diverse team of collaborators from North America and South America, and will develop collaborations with high-altitude physiologists. A postdoc, graduate students, and undergrads, will be mentored by faculty conducting research in structural biology, biochemical physiology, and population genomics. Understanding the mechanistic basis of traits that underlie adaptation to high-altitude environments will be motivational for the conservation of Andean species, as well as their habitats. This collaborative award is co-funded by the NSF Division of Integrative Organismal Systems and by the NSF Office of International Science and Engineering, Americas Program.
While evolutionary outcomes are often predictable the pathways by which convergent evolution occurs can be idiosyncratic. Convergent changes in protein function can occur through molecular changes that can be biochemically similar or dissimilar and through historical pathways that may involve unique substitutions, parallel substitutions, or selection on pre-existing genetic variation. At high altitude organisms are confronted by physiological challenges resulting from hypoxia caused by the lower partial pressure of O2 (PO2), which can impose severe constraints on aerobic metabolism. We conducted an experimental analysis of hemoglobin (Hb) function, including recombinant Hb, demonstrating that increased Hb-O2 affinity in eight species of Andean waterfowl has evolved by different mechanistic and historical pathways. Among these eight duck species in the high Andes, P50 for purified HbA for most low-altitude populations ranged from 35 to 42 Torr, whereas high-altitude genotypic variants exhibited P50 from 25 to 35 Torr. While the end result may have been the same for each high-altitude population, resulting in left-shifted Hb-O2 affinity, the biochemical mechanisms themselves and historical pathways have been largely idiosyncratic involving a combination of structural and allosteric modifications, as well as unique, parallel, and collateral substitutions that have evolved Hb-O2 affinity in the same direction by different evolutionary processes. Finally, the strength of selection on Hb-O2 affinity appears to be strong, as the observed HbA polymorphisms had the highest observed FST in genome-wide scans comparing low- and high-altitude population pairs within species.
