TY - JOUR
T1 - Natural selection contributed to immunological differences between hunter-gatherers and agriculturalists
AU - Harrison, Genelle F.
AU - Sanz, Joaquin
AU - Boulais, Jonathan
AU - Mina, Michael J.
AU - Grenier, Jean Christophe
AU - Leng, Yumei
AU - Dumaine, Anne
AU - Yotova, Vania
AU - Bergey, Christina M.
AU - Nsobya, Samuel L.
AU - Elledge, Stephen J.
AU - Schurr, Erwin
AU - Quintana-Murci, Lluis
AU - Perry, George H.
AU - Barreiro, Luis B.
N1 - Funding Information:
The authors thank the Batwa and Bakiga communities and all individuals who participated in this study; also the Batwa Development Program, J. Byaruhanga, M. Magambo, P. Byamugisha, S. Twesigomwe, J. Safari and L. Busingye for expert assistance during the sample collection process in Uganda. We thank S. Nanyunja for technical laboratory assistance. We thank J. Tung and L.B.B. laboratory members for critical reading of the manuscript. We thank Calcul Québec and Compute Canada for providing access to the supercomputer Briaree from the University of Montreal. This work was supported by NIH R01-GM115656 to G.H.P and L.B.B., a fellowship from the Réseau de Médecine Génétique Appliquée and the Fonds de Recherche du Québec− Santé to G.F.H, and 1 F32 GM125228-638 01A1 to C.M.B. RNA-seq data have been deposited in Gene Expression Omnibus (accession number GSE120502). The 1M SNP genotype data are available at the European Genome–Phenome archive, www.ebi.ac.uk/ ega/ (accession numbers EGAS00001000605 and EGAS00001000908).
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.
AB - 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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U2 - 10.1038/s41559-019-0947-6
DO - 10.1038/s41559-019-0947-6
M3 - Article
C2 - 31358949
AN - SCOPUS:85069912062
VL - 3
SP - 1253
EP - 1264
JO - Nature Ecology and Evolution
JF - Nature Ecology and Evolution
SN - 2397-334X
IS - 8
ER -