Human Biology Volume 85 Issue 1 Special Issue on Revisiting the "Negrito" Article 12 Hypothesis 2013 Evolution of the Pygmy Phenotype: Evidence of Positive Selection from Genome-wide Scans in African, Asian, and Melanesian Pygmies Andrea Bamberg Migliano Department of Anthropology, University College London, London, UK, [email protected] Irene Gallego Romero Leverhulme Centre for Human Evolutionary Studies, Department of Biological Anthropology, University of Cambridge, Cambridge, UK Mait Metspalu Department of Evolutionary Biology, University of Tartu and Estonian Biocentre, Tartu, Estonia Matthew Leavesley Archaeology Department, James Cook University, Cairns, Australia Luca Pagani Leverhulme Centre for Human Evolutionary Studies, Department of Biological Anthropology, University of Cambridge, Cambridge, UK Recommended Citation Migliano, Andrea Bamberg; Romero, Irene Gallego; Metspalu, Mait; Leavesley, Matthew; Pagani, Luca; Antao, Tiago; Huang, Da-Wei; Sherman, Brad T.; Siddle, Katharine; Scholes, Clarissa; Hudjashov, Georgi; Kaitokai, Elton; Babalu, Avis; Belatti, Maggie; Cagan, Alex; Hopkinshaw, Bryony; Shaw, Colin; Nelis, Mari; Metspalu, Ene; Mägi, Reedik; Lempicki, Richard A.; Villems, Richard; Lahr, Marta Mirazon; and Kivisild, Toomis (2013) "Evolution of the Pygmy Phenotype: Evidence of Positive Selection from Genome-wide Scans in African, Asian, and Melanesian Pygmies," Human Biology: Vol. 85: Iss. 1, Article 12. Available at: http://digitalcommons.wayne.edu/humbiol/vol85/iss1/12 Tiago Antao Leverhulme Centre for Human Evolutionary Studies, Department of Biological Anthropology, University of Cambridge, Cambridge, UK Da-Wei Huang Laboratory of Immunopathogenesis and Bioinformatics, Clinical Services Program, SAIC-Frederick Inc., National Cancer Institute at Frederick, Frederick, MD Brad T. Sherman Laboratory of Immunopathogenesis and Bioinformatics, Clinical Services Program, SAIC-Frederick Inc., National Cancer Institute at Frederick, Frederick, MD See next page for additional authors Follow this and additional works at: http://digitalcommons.wayne.edu/humbiol Part of the Biological and Physical Anthropology Commons, and the Genetics and Genomics Commons Evolution of the Pygmy Phenotype: Evidence of Positive Selection from Genome-wide Scans in African, Asian, and Melanesian Pygmies Abstract 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. Keywords Pygmies, Negritos, Evolution, Phenotype, Genotype, Natural Selection, Convergent Adaptation Authors 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, and Toomis Kivisild This open access article is available in Human Biology: http://digitalcommons.wayne.edu/humbiol/vol85/iss1/12 Evolution of the Pygmy Phenotype: Evidence of Positive Selection from Genome-wide Scans in African, Asian, and Melanesian Pygmies 1 2 3 ANDREA BAMBERG MIGLIANO, * IRENE GALLEGO ROMERO, MAIT METSPALU, MATTHEW 4 2 2 5 5 LEAVESLEY, LUCA PAGANI, TIAGO ANTAO, DA-WEI HUANG, BRAD T. SHERMAN, 2 2 3 6 KATHARINE SIDDLE, CLARISSA SCHOLES, GEORGI HUDJASHOV, ELTON KAITOKAI, AVIS 6 2 2 2 2 BABALU, MAGGIE BELATTI, ALEX CAGAN, BRYONY HOPKINSHAW, COLIN SHAW, MARI 3 3 3,7 5 3 NELIS, ENE METSPALU, REEDIK MÄGI, RICHARD A. LEMPICKI, RICHARD VILLEMS, 2† 2,3† MARTA MIRAZON LAHR, AND TOOMAS KIVISILD Abstract 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 cessa- tion 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 1Department of Anthropology, University College London, London, UK. 2Leverhulme Centre for Human Evolutionary Studies, Department of Biological Anthropology, University of Cambridge, Cambridge, UK. 3Department of Evolutionary Biology, University of Tartu and Estonian Biocentre, Tartu, Estonia. 4Archaeology Department, James Cook University, Cairns, Australia. 5Laboratory of Immunopathogenesis and Bioinformatics, Clinical Services Program, SAIC-Frederick Inc., National Cancer Institute at Frederick, Frederick, MD. 6University of Papua New Guinea, Port Moresby, Papua New Guinea. 7Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, University of Ox- ford, Oxford, UK. *Correspondence to: Andrea Bamberg Migliano, Department of Anthropology, University College London, London WC1E 6BT. E-mail: [email protected]. †These authors contributed equally to the manuscript and share the senior authorship. Research was developed at the Leverhulme Centre for Human Evolutionary Studies, Department of Biologi- cal Anthropology, University of Cambridge, and at the Department of Evolutionary Biology, University of Tartu and Estonian Biocentre. Human Biology, February–June 2013, v. 85, no. 1–3, pp. 251–284. Copyright © 2013 Wayne State University Press, Detroit, Michigan 48201-1309 KEY WORDS: PYGMIES, NEGRITOS, EVOLUTION, PHENOTYPE, GENOTYPE, NATURAL SE- LECTION, CONVERGENT ADAPTATION. 252 / MIGLIANO ET AL. 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. The term negrito has been used in the literature to refer to short-statured hunter- gatherers living in Asia, Southeast Asia, and Melanesia (Andaman Islands, Peninsula Malaysia, and the Philippines). The term pygmy has sometimes been used to refer to short-statured populations in Africa, but in other publications, the term pygmy is used to refer to short-statured populations in general (both in and outside of Africa). Here we are concerned with the evolution of short stature in human populations; we use the term pygmy to refer to all the short-statured populations, and when necessary to distinguish Asian and Melanesian groups, we use the term negrito. We do not intend to imply common origin when applying the terms pygmy and negrito; we use the terms to describe a particular phenotype. Pygmy populations, character- ized by their extremely short adult stature (average adult male height < 155 cm; Cavalli-Sforza 1986; Migliano et al. 2007), exist in Africa, the Andaman Islands, Peninsula Malaysia, the Philippines, and Papua New Guinea (Figure 1). While early researchers speculated that existence of short-statured peoples in scattered locations across the world (known as pygmies in the west of the Old World and negritos in the east) was associated with a single primordial migration of pygmy peoples, recent work has shown that, by and large, short-statured populations worldwide are more closely related to their neighbor populations