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Study Considers Lifestyle-Related Epigenome Differences in Central African Populations

NEW YORK (GenomeWeb) – A French- and Canadian-led team took a look at blood methylation patterns in individuals from hunter-gatherer and agrarian groups in a rainforest region of Central Africa, uncovering epigenetic shifts that appear to track with the traditional and current environments and lifestyles of these populations.

As they reported online today in Nature Communications, the researchers did array-based epigenome profiling in blood samples from hundreds of Central African individuals belonging to either rainforest hunter-gatherer, a.k.a. 'pygmy,' or more sedentary agrarian populations from the same region, including individuals from a traditional farming group that have more recently become accustomed to forest life.

Along with population-related methylation differences with ties to genetic variants that appear to have been under selection in either the rainforest hunter-gatherer or agrarian groups, the team identified epigenetic patterns that appear to coincide with both the traditional and current environments of the Central African populations considered.

"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," corresponding author Lluis Quintana-Murci, a human evolutionary genetics researcher affiliated with the Pasteur Institute and the French National Centre for Scientific Research, and his colleagues wrote.

"Specifically," they explained, "methylation variation associated with recent changes in habitat mostly concerns immune and cellular functions, whereas that associated with historical lifestyle affects developmental processes."

The team used Illumina 450K arrays to profile genome-wide SNP and methylation patterns in blood samples from 267 individuals from Gabon and/or Cameroon — a set that included 112 individuals from a rainforest hunter-gatherer group, 94 traditionally agrarian individuals living in a deforested urban area, and 61 individuals from a traditionally agrarian population called the Nzime that now lives and hunts in a forested region.

Similar approaches were used to profile whole-blood DNA methylation patterns in another 47 rainforest hunter-gatherers and 48 agrarian individuals from Ugandan populations living in the eastern Central African belt.

Following quality control steps, the researchers were left with DNA methylation data at more than 360,000 genome-wide sites in 352 of the 362 individuals tested.

Overall, the most pronounced DNA methylation differences appeared in individuals from rainforest hunter-gatherer and agrarian populations, they reported, regardless of the populations' locale or their current lifestyle.

For example, the team saw methylation differences at more than 25,800 sites in the genome when they compared samples from traditional hunter-gatherer and agrarian groups sampled in Gabon and Cameroon. In samples from Uganda, meanwhile, some 19,401 regions were differentially methylated depending on historical lifestyle, including 6,844 of the same sites highlighted in the eastern population comparison.

Methylation differences also turned up in rainforest populations with historical lifestyle differences that currently live in similar environments, the researchers noted, typically appearing in regions expected to alter the regulation of developmental, anatomical, and growth-related genes.

Nevertheless, their results pointed to parts of the genome where methylation changes tended to occur in the farming population that recently became more adept at hunting in the rainforest, including methylation changes affecting the gene bodies and distal promoters of genes involved in immunity, pathogen response, and cellular functions.

When they looked at the relationship between sequence variants and lifestyle-related methylation shifts, meanwhile, the researchers found an over-representation of quantitative trait loci involving sites that are differentially methylated in populations with different historical populations. And many of these SNPs fell in parts of the genome that are believed to have undergone positive selection, particularly in the agrarian groups.

"Collectively, these findings suggest that positive selection has targeted DNA sequence variants that influence — directly and indirectly — variation in DNA methylation," the study's authors noted.

"That these signals appear to be more pronounced among agriculturist populations, both in the western and eastern settings, suggests the occurrence of increased local adaptation targeting regulatory variation in these human groups," they added.

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