• Altmetrics
  • Sign up for PNAS eTOC alerts

Adaptive, convergent origins of the pygmy phenotype in African rainforest hunter-gatherers

  1. Luis B. Barreirod,n,1,2
  1. aDepartments of Anthropology and Biology, Pennsylvania State University, University Park, PA 16802;
  2. bSchool of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland;
  3. cSwiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;
  4. dSainte-Justine Hospital Research Centre, Montreal, QC, Canada H3T 1C5;
  5. eInstitut Pasteur, Unit of Human Evolutionary Genetics, 75015 Paris, France;
  6. fCentre National de la Recherche Scientifique, URA3012, 75015 Paris, France;
  7. gDepartment of Biochemistry, Faculty of Medicine, University of Montreal, Montreal, QC, Canada H3T 1C5;
  8. hSchool of Computer Science, and
  9. iDepartment of Human Genetics, McGill University, Montreal, QC, Canada H3A 1B1;
  10. jDepartments of Statistics and Human Genetics, University of Chicago, Chicago, IL 60637;
  11. kDepartment of Pathology, Makerere University, Kampala, Uganda;
  12. lInstitute of Ecology and Evolution, University of Bern, 3012 Bern, Switzerland;
  13. mDepartments of Anthropology and Biological Sciences, Dartmouth College, Hanover, NH 03755; and
  14. nDepartment of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, QC, Canada H3T 1C5

  1. Edited by Noël Cameron, Loughborough University, Leicestershire, United Kingdom, and accepted by the Editorial Board July 22, 2014 (received for review February 16, 2014)

Significance

Tropical rainforest hunter-gatherer populations worldwide share the pygmy phenotype, or small human body size. The evolutionary history of this phenotype is largely unknown. Here we studied DNA from the Batwa, a rainforest hunter-gatherer population from east central Africa, to identify regions of the Batwa genome that underlie the pygmy phenotype. We then performed population genomic analyses to study the evolution of these regions, including comparisons with the Baka, a west central African rainforest hunter-gatherer population. We conclude that the pygmy phenotype likely arose due to positive natural selection and that it arose possibly multiple times within Africa. These results support longstanding anthropological hypotheses that small body size confers an important selective advantage for human 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.

Footnotes

  • ↵1G.H.P., M.F., and L.B.B. contributed equally to this work.

  • ↵2To whom correspondence may be addressed. Email: ghp3{at}psu.edu or luis.barreiro{at}umontreal.ca.

  • Author contributions: G.H.P., N.J.D., and L.B.B. designed research; G.H.P. and L.B.B. performed research; G.H.P., S.N., L.Q.-M., N.J.D., and L.B.B. contributed new reagents/analytic tools; G.H.P., M.F., J.-C.G., E.P., Y.N., A.P., M.B., S.G., X.Z., L.E., and L.B.B. analyzed data; and G.H.P. and L.B.B. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission. N.C. is a guest editor invited by the Editorial Board.

  • Data deposition: The 1M SNP genotype data for the Baka, Nzebi, and Nzemi and for 40 Batwa and 40 Bakiga individuals were reported in Patin et al. (11) and are available at the European Genome-Phenome archive, www.ebi.ac.uk/ega/ (accession no. EGAS00001000605). The 1M SNP genotype data for the remaining 129 Batwa and 21 Bakiga individuals have been deposited in the European Genome-Phenome archive (accession no. EGAS00001000908). The per-SNP and per-individual HAPMIX estimates of local ancestry, the per-SNP P values and q values (false-discovery rate) from the admixture mapping and GEMMA analyses, and the per-SNP pairwise FST values and population-specific iHS values have been deposited in the Dryad Digital Repository (doi:10.5061/dryad.ms8k7).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1402875111/-/DCSupplemental.

Online Impact