Natural selection has contributed to functional immune response differences between human hunter-gatherers and agriculturalists
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA493229 | ENA |
REPOSITORIES: ENA
Dataset's files
| 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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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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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 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:Individuals from different populations vary considerably in their susceptibility to immune-related diseases. To understand how genetic variation and natural selection contribute to these differences, we tested for the effects of African versus European ancestry on the transcriptional response of primary macrophages to live bacterial pathogens. A total of 9.3% of macrophage-expressed genes show ancestry-associated differences in the gene regulatory response to infection, and African ancestry specifically predicts a stronger inflammatory response and reduced intracellular bacterial growth. A large proportion of these differences are under genetic control: for 804 genes, more than 75% of ancestry effects on the immune response can be explained by a single cis- or trans-acting expression quantitative trait locus (eQTL). Finally, we show that genetic effects on the immune response are strongly enriched for recent, population-specific signatures of adaptation. Together, our results demonstrate how historical selective events continue to shape human phenotypic diversity today, including for traits that are key to controlling infection.
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