title: Adaptive, convergent origins of the pygmy phenotype in African rainforest hunter-gatherers.
abstract: The evolutionary history of the human pygmy phenotype (small body size), a characteristic of African and Southeast Asian rainforest hunter-gatherers, is largely unknown. Here we use a genome-wide admixture mapping analysis to identify 16 genomic regions that are significantly associated with the pygmy phenotype in the Batwa, a rainforest hunter-gatherer population from Uganda (east central Africa). The identified genomic regions have multiple attributes that provide supporting evidence of genuine association with the pygmy phenotype, including enrichments for SNPs previously associated with stature variation in Europeans and for genes with growth hormone receptor and regulation functions. To test adaptive evolutionary hypotheses, we computed the haplotype-based integrated haplotype score (iHS) statistic and the level of population differentiation (FST) between the Batwa and their agricultural neighbors, the Bakiga, for each genomic SNP. Both |iHS| and FST values were significantly higher for SNPs within the Batwa pygmy phenotype-associated regions than the remainder of the genome, a signature of polygenic adaptation. In contrast, when we expanded our analysis to include Baka rainforest hunter-gatherers from Cameroon and Gabon (west central Africa) and Nzebi and Nzime neighboring agriculturalists, we did not observe elevated |iHS| or FST values in these genomic regions. Together, these results suggest adaptive and at least partially convergent origins of the pygmy phenotype even within Africa, supporting the hypothesis that small body size confers a selective advantage for tropical rainforest hunter-gatherers but raising questions about the antiquity of this behavior.
authors.affiliation: Departments of Anthropology and Biology, Pennsylvania State University, University Park, PA 16802; ghp3@psu.edu luis.barreiro@umontreal.ca.
authors.forename: George H
authors.initials: GH
authors.lastname: Perry
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;
authors.forename: Matthieu
authors.initials: M
authors.lastname: Foll
authors.affiliation: Sainte-Justine Hospital Research Centre, Montreal, QC, Canada H3T 1C5;
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Grenier
authors.affiliation: Institut Pasteur, Unit of Human Evolutionary Genetics, 75015 Paris, France; Centre National de la Recherche Scientifique, URA3012, 75015 Paris, France;
authors.forename: Etienne
authors.initials: E
authors.lastname: Patin
authors.affiliation: Sainte-Justine Hospital Research Centre, Montreal, QC, Canada H3T 1C5; Department of Biochemistry, Faculty of Medicine, University of Montreal, Montreal, QC, Canada H3T 1C5;
authors.forename: Yohann
authors.initials: Y
authors.lastname: Nédélec
authors.affiliation: Sainte-Justine Hospital Research Centre, Montreal, QC, Canada H3T 1C5; Department of Biochemistry, Faculty of Medicine, University of Montreal, Montreal, QC, Canada H3T 1C5;
authors.forename: Alain
authors.initials: A
authors.lastname: Pacis
authors.affiliation: School of Computer Science, and.
authors.forename: Maxime
authors.initials: M
authors.lastname: Barakatt
authors.affiliation: Department of Human Genetics, McGill University, Montreal, QC, Canada H3A 1B1;
authors.forename: Simon
authors.initials: S
authors.lastname: Gravel
authors.affiliation: Departments of Statistics and Human Genetics, University of Chicago, Chicago, IL 60637;
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Makerere University, Kampala, Uganda;
authors.forename: Sam L
authors.initials: SL
authors.lastname: Nsobya
authors.affiliation: Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland; Institute of Ecology and Evolution, University of Bern, 3012 Bern, Switzerland;
authors.forename: Laurent
authors.initials: L
authors.lastname: Excoffier
authors.affiliation: Institut Pasteur, Unit of Human Evolutionary Genetics, 75015 Paris, France; Centre National de la Recherche Scientifique, URA3012, 75015 Paris, France;
authors.forename: Lluis
authors.initials: L
authors.lastname: Quintana-Murci
authors.affiliation: Departments of Anthropology and Biological Sciences, Dartmouth College, Hanover, NH 03755; and.
authors.forename: Nathaniel J
authors.identifier: 0000-0001-5916-418X
authors.initials: NJ
authors.lastname: Dominy
authors.affiliation: Sainte-Justine Hospital Research Centre, Montreal, QC, Canada H3T 1C5; Institute of Ecology and Evolution, University of Bern, 3012 Bern, Switzerland; ghp3@psu.edu luis.barreiro@umontreal.ca.
authors.forename: Luis B
authors.initials: LB
authors.lastname: Barreiro
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D005075:Biological Evolution; D044383:Black People / Q000235:genetics*; D049628:Body Size / Q000235:genetics*; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic / Q000235:genetics; D014454:Uganda
keywords: convergent evolution; human evolutionary ecology; human hunter-gatherers; population genomics