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 haplotypebased integrated haplotype score (iHS) statistic and the level of population differentiation (F ST ) between the Batwa and their agricultural neighbors, the Bakiga, for each genomic SNP. Both jiHSj and F ST 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 jiHSj or F ST 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.human evolutionary ecology | human hunter-gatherers | population genomics | convergent evolution

Factors influencing the effect size distribution of adaptive substitutions

“…By contrast, although statistical power was limited, a study that examined differences among a human pygmy population and their agricultural neighbours [46] found evidence for a higher frequency of large-effect alleles. The pygmy form evolved independently at least three times following the colonization of tropical rainforest [44,46,47], suggesting that it might represent an adaptation to a new environment. This example highlights the need to evaluate effect size distributions in light of the evolutionary history of studied populations.…”

Going global by adapting local: A review of recent human adaptation

“…The short stature trait is an example of convergent evolution in rainforest hunter-gatherer (RFHG) populations across Africa, Asia, and South America. Selection for small body size may be due to limited food resources, resistance to heat stress, immune response, and/or a trade-off between early onset of reproduction and cessation of growth (14, 15). Perturbations in the GH1-IGF1 pathway have been implicated to play a role in short stature in RFHG populations in central Africa and southeast Asia (16).…”

“…This haplotype was not tagged in previous genotyping arrays, demonstrating the importance of including ethnically diverse populations in whole-genome sequencing studies (18). However, RFHG and neighboring agriculturalist populations in Uganda exhibit a distinct set of loci associated with short stature, which raises the possibility of convergent evolution of this trait across the RFHGs in Africa (15). …”

Inferences of African evolutionary history from genomic data

“…a genetic variant at SLC24A5 associated with light skin in non-Africans was identified in zebrafish [46]), or by genotype/phenotype association studies. Some prominent examples which integrate genome-wide scans of selection with genotype/phenotype association studies or other functional assays in Africans include bitter taste perception [47], adaptation to diverse diets [43,48,49,50 • ], high-altitude adaptation [51,52], short stature in CAHG [20,53,54 • ], and immune response [39,55–60], a few of which are discussed here in greater detail.…”

“…For example, the short stature phenotype of CAHG populations has been proposed as an adaptive phenotype for a tropical forest environment [20,53,54 • ,68–70]. Jarvis et al .…”