Whole genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection

Abstract

(250 words in total)28 African Pygmies practicing a mobile hunter-gatherer lifestyle are phenotypically and genetically diverged 29 from other anatomically modern humans, and they likely experienced strong selective pressures due to 30 their unique lifestyle in the Central African rainforest. To identify genomic targets of adaptation, we 31 sequenced the genomes of four Biaka Pygmies from the Central African Republic and jointly analyzed 32 these data with the genome sequences of three Baka Pygmies from Cameroon and nine Yoruba famers. 33To account for the complex demographic history of these populations that includes both isolation and 34 gene flow, we fit models using the joint allele frequency spectrum and validated them using independent 35 approaches. Our two best-fit models both suggest ancient divergence between the ancestors of the farmers 36 and Pygmies, 90,000 or 150,000 years ago. We also find that bi-directional asymmetric gene-flow is 37 statistically better supported than a single pulse of unidirectional gene flow from farmers to Pygmies, as 38 previously suggested. We then applied complementary statistics to scan the genome for evidence of 39 selective sweeps and polygenic selection. We found that conventional statistical outlier approaches were 40 biased toward identifying candidates in regions of high mutation or low recombination rate. To avoid this 41 bias, we assigned P-values for candidates using whole-genome simulations incorporating demography 42 and variation in both recombination and mutation rates. We found that genes and gene sets involved in

Model-based analyses of whole-genome data reveal a complex evolutionary history involving archaic introgression in Central African Pygmies

“…To assess the efficacy of this LD approach under a complex demographic model, we applied this method to simulated whole-genome data with archaic admixture. Simulations were generated by incorporating various scenarios of archaic admixture into the best-fit demographic model for Western African Pygmies described in Hsieh et al (2016), which includes population divergence, population isolation, and recent asymmetric gene flow (Methods; Supplemental Figs. S2, S10).…”

“…: 5.7-9.6 kya) . African Pygmies have undergone extensive gene flow with neighboring farmers (Patin et al 2009;Tishkoff et al 2009;Jarvis et al 2012;Hsieh et al 2016), and recent studies suggest that some Western African populations, including the Niger-Kodorfanian Yoruba farmers from Nigeria, show strong signals of ancient admixture (Plagnol and Wall 2006;Wall et al 2009). Thus, it is plausible that archaic lineages associated with this inferred admixture event introgressed recently into one or more non-Pygmy African populations, such as the ancestors of African farmers, and subsequently entered the Pygmy population through recent gene flow from these non-Pygmy neighboring groups.…”

“…Models underlying these simulations were based on Hammer et al (2011), and the best-fit demographic model (Model-1) (Supplemental Fig. S2A) was taken from Hsieh et al (2016). Because we are interested in parameters related…”

“…Cold Spring Harbor Laboratory Press on May 10, 2018 -Published by genome.cshlp.org Downloaded from to archaic admixture, for simplicity we fixed other parameters, including the effective population sizes for the ancestors of modern humans, Pygmies, and farmer populations, times of divergence between populations, as well as the asymmetric gene-flow between Pygmy and farmer populations, as described in Hammer et al (2011) andHsieh et al (2016). In addition, we assumed the same population size (6700 individuals) for both the common ancestor of archaic/modern humans and the archaic human population.…”

The demographic history and mutational load of African hunter-gatherers and farmers

“…By contrast, the neighboring sedentary populations practice agriculture, and are known to have recently expanded across sub-Saharan Africa 33 . These contrasting lifestyles are associated with differences in the demographic histories of these populations, but some aspects of the genetic and demographic histories of rainforest hunter-gatherers and farmers remain unclear, given the highly heterogeneous nature of the genetic data used and the limited sample sizes included in earlier studies [34][35][36][37][38][39] . Furthermore, signatures of recent demographic change can be detected only if the full site frequency spectrum is obtained from sequencing data for relatively large sample sizes, a condition not met by any of the previous studies of these populations.…”