Abstract
The distribution of deleterious genetic variation across human populations is a key issue in evolutionary biology and medical genetics. However, the impact of different modes of subsistence on recent changes in population size, patterns of gene flow, and deleterious mutational load remains to be fully characterized. We addressed this question, by generating 300 high-coverage exome sequences from various populations of rainforest hunter-gatherers and neighboring farmers from the western and eastern parts of the central African equatorial rainforest. We show here, by model-based demographic inference, that the effective population size of African populations remained fairly constant until recent millennia, during which the populations of rainforest hunter-gatherers have experienced a ∼75% collapse and those of farmers a mild expansion, accompanied by a marked increase in gene flow between them. Despite these contrasting demographic patterns, African populations display limited differences in the estimated distribution of fitness effects of new nonsynonymous mutations, consistent with purifying selection against deleterious alleles of similar efficiency in the different populations. This situation contrasts with that we detect in Europeans, which are subject to weaker purifying selection than African populations. Furthermore, the per-individual mutation load of rainforest hunter-gatherers was found to be similar to that of farmers, under both additive and recessive modes of inheritance. Together, our results indicate that differences in the subsistence patterns and demographic regimes of African populations have not resulted in large differences in mutational burden, and highlight the role of gene flow in reshaping the distribution of deleterious genetic variation across human populations.
Significance Statement The last 100,000 years of human history have been characterized by important demographic events, including population splits, size changes and gene flow, potentially affecting the distribution of deleterious mutations across populations and, ultimately, disease risk. We sequenced the exomes of various African rainforest hunter-gatherer and sedentary farming populations, reconstructed their demographic histories, and explored the effects of differences in lifestyles and demography on mutational load. We found that the recent demographic histories of hunter-gatherers and farmers differed considerably, with population collapses for hunter-gatherers and population expansions for farmers. However, these contrasted pasts have not translated into major differences in the efficiency of purifying selection against deleterious alleles, leading to a similar mutational burden in the two groups.
