Evolution of the Pygmy Phenotype: Evidence of Positive Selection from Genome-wide Scans in African, Asian, and Melanesian Pygmies

Andrea Bamberg Migliano, Irene Gallego Romero, Mait Metspalu, Matthew Leavesley, Luca Pagani, Tiago Antao, Da-Wei Huang, Brad T. Sherman, Katharine Siddle, Clarissa Scholes, Georgi Hudjashov, Elton Kaitokai, Avis Babalu, Maggie Belatti, Alex Cagan, Bryony Hopkinshaw, Colin Shaw, Mari Nelis, Ene Metspalu, Reedik Mägi, Richard A. Lempicki, Richard Villems, Marta Mirazon Lahr, Toomas Kivisild

Human pygmy populations inhabit different regions of the world, from Africa to Melanesia. In Asia, short-statured populations are often referred to as "negritos." Their short stature has been interpreted as a consequence of thermoregulatory, nutritional, and/or locomotory adaptations to life in tropical forests. A more recent hypothesis proposes that their stature is the outcome of a life history trade-off in high-mortality environments, where early reproduction is favored and, consequently, early sexual maturation and early growth cessation have coevolved. Some serological evidence of deficiencies in the growth hormone/insulin-like growth factor axis have been previously associated with pygmies' short stature. Using genome-wide single-nucleotide polymorphism genotype data, we first tested whether different negrito groups living in the Philippines and Papua New Guinea are closely related and then investigated genomic signals of recent positive selection in African, Asian, and Papuan pygmy populations. We found that negritos in the Philippines and Papua New Guinea are genetically more similar to their nonpygmy neighbors than to one another and have experienced positive selection at different genes. These results indicate that geographically distant pygmy groups are likely to have evolved their short stature independently. We also found that selection on common height variants is unlikely to explain their short stature and that different genes associated with growth, thyroid function, and sexual development are under selection in different pygmy groups.