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Natural selection has contributed to functional immune response differences between human hunter-gatherers and agriculturalists

ABSTRACT: Natural selection has contributed to functional immune response differences between human hunter-gatherers and agriculturalists

PROVIDER: PRJNA493229 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7904530.fastq.gz	Fastqsanger.gz
	SRR7904540.fastq.gz	Fastqsanger.gz
	SRR7904550.fastq.gz	Fastqsanger.gz
	SRR7904560.fastq.gz	Fastqsanger.gz
	SRR7904570.fastq.gz	Fastqsanger.gz

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Natural selection has contributed to functional immune response differences between human hunter-gatherers and agriculturalists

Project description:The shift from a hunter-gatherer (HG) to an agricultural (AG) mode of subsistence is believed to have been associated with profound changes in the burden and diversity of pathogens across human populations. Yet, the extent to which the advent of agriculture impacted the evolution of the human immune system remains unknown. Here we present a comparative study of variation in the transcriptional responses of peripheral blood mononuclear cells (PBMCs) to bacterial and viral stimuli between the Batwa, a rainforest hunter-gatherer, and the Bakiga, an agriculturalist population from Central Africa. We observed increased divergence between hunter-gatherers and farmers in the transcriptional response to viruses compared to that for bacterial stimuli. We demonstrate that a significant fraction of these transcriptional differences are under genetic control, and we show that positive natural selection has helped to shape population differences in immune regulation. Unexpectedly, we found stronger signatures of recent natural selection in the rainforest hunter-gatherers, which argues against the popularized notion that shifts in pathogen exposure due to the advent of agriculture imposed radically heightened selective pressures in agriculturalist populations.

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Natural selection contributed to immunological differences between hunter-gatherers and agriculturalists.

Project description:The shift from a hunter-gatherer to an agricultural mode of subsistence is believed to have been associated with profound changes in the burden and diversity of pathogens across human populations. Yet, the extent to which the advent of agriculture affected the evolution of the human immune system remains unknown. Here we present a comparative study of variation in the transcriptional responses of peripheral blood mononuclear cells to bacterial and viral stimuli between Batwa rainforest hunter-gatherers and Bakiga agriculturalists from Uganda. We observed increased divergence between hunter-gatherers and agriculturalists in the early transcriptional response to viruses compared with that for bacterial stimuli. We demonstrate that a significant fraction of these transcriptional differences are under genetic control and we show that positive natural selection has helped to shape population differences in immune regulation. Across the set of genetic variants underlying inter-population immune-response differences, however, the signatures of positive selection were disproportionately observed in the rainforest hunter-gatherers. This result is counter to expectations on the basis of the popularized notion that shifts in pathogen exposure due to the advent of agriculture imposed radically heightened selective pressures in agriculturalist populations.

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Project description:The genetic structure of the indigenous hunter-gatherer peoples of Southern Africa, the oldest known lineage of modern man, holds an important key to understanding humanity's early history. Previously sequenced human genomes have been limited to recently diverged populations. Here we present the first complete genome sequences of an indigenous hunter-gatherer from the Kalahari Desert and of a Bantu from Southern Africa, as well as protein-coding regions from an additional three hunter-gatherers from disparate regions of the Kalahari. We characterize the extent of whole-genome and exome diversity among the five men, reporting 1.3 million novel DNA differences genome-wide, and 13,146 novel amino-acid variants. These data allow genetic relationships among Southern African foragers and neighboring agriculturalists to be traced more accurately than was previously possible. Adding the described variants to current databases will facilitate inclusion of Southern Africans in medical research efforts.

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Project description: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 unclear. Here, we report high-coverage exomes from various populations of rainforest hunter-gatherers and farmers from central Africa. We find that the recent demographic histories of hunter-gatherers and farmers differed considerably, with population collapses for hunter-gatherers and expansions for farmers, accompanied by increased gene flow. We show that purifying selection against newly arising deleterious alleles is of similar efficiency across African populations, in contrast with Europeans where we detect weaker purifying selection. Furthermore, the per-individual mutation load of rainforest hunter-gatherers is similar to that of farmers, under both additive and recessive models. Our results indicate that differences in the cultural practices and demographic regimes of African populations have not resulted in large differences in mutational burden, and highlight the beneficial role of gene flow in reshaping the distribution of deleterious genetic variation across human populations.

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