The epigenomic landscape of African rainforest hunter-gatherers and farmers

Abstract

The genetic history of African populations is increasingly well documented, yet their patterns of epigenomic variation remain uncharacterized. Moreover, the relative impacts of DNA sequence variation and temporal changes in lifestyle and habitat on the human epigenome remain unknown. Here we generate genome-wide genotype and DNA methylation profiles for 362 rainforest hunter-gatherers and sedentary farmers. We find that the current habitat and historical lifestyle of a population have similarly critical impacts on the methylome, but the biological functions affected strongly differ. Specifically, methylation variation associated with recent changes in habitat mostly concerns immune and cellular functions, whereas that associated with historical lifestyle affects developmental processes. Furthermore, methylation variation—particularly that correlated with historical lifestyle—shows strong associations with nearby genetic variants that, moreover, are enriched in signals of natural selection. Our work provides new insight into the genetic and environmental factors affecting the epigenomic landscape of human populations over time.

Genetic Diversity, Epigenetic Reprogramming and Environmental Factors: Leading Directions in the Study of the Complex Human Diseases

“…Maud Fagny and colleagues (61) have found that the current habitat and historical lifestyle of a population have similarly critical impacts on the methylome, but the biological functions affected differ strongly. Specifically, the methylation variation associated with recent changes in habitat mostly concerns immune and cellular functions, whereas the variation associated with historical lifestyle affects developmental processes.…”

“…Maud Fagny and colleagues have suggested that populations can initially respond to environmental challenges via epigenetic changes, uncoupled from variation in the DNA sequence, with the adaptive phenotype increasingly being achieved via genetic changes as time passes. (61) It has also been suggested that epigenetic changes may account for the missing heritability determinants of complex diseases, such as atherosclerosis, hypertension, metabolic syndrome, and diabetes. (42)(43)(44)(45)62) Hyperhomocysteinemia in atherosclerosis is perhaps one of the mechanisms of the phenomenon of total DNA hypomethylation, characterizing, apparently, both the onset and progression of the disease.…”

“…(56) In addition, the activated estrogen receptors increase the expression/activity of NO synthase, and hence the production of NO itself, which also has the ability to inhibit the proliferation of SMCs in the vessels. (57) Recent studies have shown that differences in DNA methylation exist between major ethnic groups, (58)(59)(60)(61) highlighting the potential contribution of epigenetic modifications to human phenotypic variation.…”

Human development, heredity and evolution

“…He is also interested in the degree of genetic and epigenetic variation in the human population, and analyzed SNP data and genome-wide DNA methylation at 450,000 sites in various African populations. He showed that historical lifestyle affects DNA methylation under genetic control at genes associated with development, such as bone density and height, whereas methylation variation associated with recent changes in habitat prominently affects loci involved in immune processes (Fagny et al, 2015). As Michael Snyder (Stanford University, USA) showed in his talk about personal ʻomics' data analyses for managing and predicting diseases, these integrative approaches -using population genetics, functional genomics and big data relating to human lifestyles -represent a powerful means to understand (epi)genotype-phenotype correlations and mechanisms of adaptation/response to environmental stresses.…”

Human evolution: a tale from ancient genomes

“…Although direct approaches based on bisulfite sequencing [154,155] and enrichment of methylated epialleles [73] have been used, the most successful approach currently available leverages on aDNA damage patterns to computationally derive genome-wide cytosine methylation and nucleosome maps [8,152,156]. Interestingly, lifestyle and socio-cultural differences are known to influence such epigenetic signatures in contemporary human groups [157]. Their persistence in aDNA molecules paves the way for an investigation of how epigenetic profiles might have been modified during major human evolutionary transitions, such as the Neolithic and the Industrial Revolution [158].…”