Global Patterns of Human Epigenetic Variation

A study of five far-flung human populations gives clues to adaptations to environmental pressures.

By Ashley Yeager | August 28, 2017

ISTOCK, BESTDESIGNSDNA methylation—changes to the activity of a DNA segment without changing the sequence—may be a rich source of raw material for natural selection, say the authors of a new study that analyzed DNA methylation, genotype, and gene expression data from five diverse human populations. They found that population-wide epigenetic changes happen much faster than changes in the DNA sequence. 

The result, published August 28 in Nature Ecology & Evolution, may offer insight into how human populations respond to environmental pressures via epigenetic responses.

The epigenome is at the interface between the genome and the environment, so studying it offers clues about different ways in which human populations respond to their surroundings, says Lluis Quintana-Murci, a human evolutionary geneticist at the Pasteur Institute in Paris who was not involved in the study. One way to adapt is through DNA sequence variation, which can be the substrate of natural selection. For instance, a mutation conferring increased resistance to malaria can increase in frequency in a given population through positive selection. But populations can respond, or possibly adapt, to environmental challenges through DNA methylation variation, too. When DNA methylation variation is under genetic control, it can be passed on through generations and participate in human adaptation, says Quintana-Murci.

“Understanding the factors driving variation in DNA methylation among populations is crucial to understanding the relationship between epigenetic diversity and phenotypic diversity, including how that diversity is related to disease,” he adds.

Research on global patterns of epigenetic diversity can be challenging to conduct, study coauthor Hunter Fraser, a geneticist at Stanford University, explains by email. For example, although scientists know that epigenetic variation plays a key role in regulating transcription, they still do not know which specific regions of the genome are involved for any given gene, and they don’t know the consequences of altering epigenetic marks such as DNA methylation, he says.

The team wanted to determine how epigenetic diversity relates to patterns of variation in DNA and gene expression at a global scale. So Fraser and colleagues looked at genetic and epigenetic data, specifically, DNA methylation at CpG sites—regions of DNA where a cytosine nucleotide occurs next to a guanine—from individuals representing five populations: six Siberian Yakuts, seven Cambodians, seven Pakistani Pathans, seven Algerian Mozabites, and seven Mexican Mayans. These are highly distinct groups, which helped the team associate epigenetic patterns to genetic and transcriptional profiles, says Holger Heyn of the Centre Nacional d'Anàlisi Genòmica in Barcelona who was not part of the research.

The results revealed a strong link between population-specific DNA methylation, mRNA levels, and genotypes. However, the CpG sites where methylation occurred that had the highest degree of population specificity were more strongly associated with a local variation in a single nucleotide (SNP) compared with the association of mRNA levels with local SNPs. Population-specific DNA methylation patterns are therefore explained better by local genetic variants than population-specific expression levels, the team says.

Because the DNA methylation variation appears to be under genetic control, it could greatly affect human adaptability. Fraser notes, however, that the consequences of methylation still aren’t clear. “It is likely that most of the variation we measured is not having any important impact, so the challenge is to figure out which genomic regions are important and how their DNA methylation impacts human traits,” he says.

To answer that question and others about epigenetic diversity, researchers will need to better understand how populations with shared environments yet different genetic backgrounds behave in terms of DNA methylation variation. They will also need to examine populations with similar genetic backgrounds but exposed to very different environments, Quintana-Murci says, adding that there’s “lots of work to be done.” As Heyn points out, “we still do not fully understand the mechanisms that drive epigenetic variation in populations.”

O. Carja et al., “Worldwide patterns of human epigenetic variation,” Nature Ecology & Evolution, doi:10.1038/s41559-017-0299-z, 2017.

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Avatar of: PastToTheFuture


Posts: 116

August 29, 2017

Amazing! Maybe Lemarck was on to something.

Avatar of: Roy Niles

Roy Niles

Posts: 115

August 29, 2017

One of these days these neoDarwinists will come to realize that the selective process operates intelligently within the individual on what might be called a trial and error basis.  Those who continue to believe that intelligence is not involved don't seem to recognize that even neoDarwinism requires biological systems to react intelligently to accidental mistkes!  So the intelligence IS there in biological systems, right?  And must have been evolving in our systems for some purpose.  Which would be to try to use an intelligent process first, rather than wait for a random mistake to be accidentally made and fail to work, so that intelligence can then be used to "correct" it and yet not used while we wait for another accidental mistake to fail.

"Adaptive mutation" is of course what we call the new self engineering procedure that many biological scientists have begun to accept - and we could just as well refer to that as "intelligent mutation" to boot.  (But not if we write articles for The Scientist)

Avatar of: James V. Kohl

James V. Kohl

Posts: 525

August 30, 2017

As Heyn points out, “we still do not fully understand the mechanisms that drive epigenetic variation in populations.”

Natural selection for energy-dependent codon optimality links RNA-directed DNA methylation to all biophysically constrained biodiversity via the pheromone-controlled physiology of reproduction. That fact seems to be missing from this representation of a failed paradigm (neo-Darwinian evolution).

Claims that facts about natural selection and epigenetic variation in populations are not fully understood can be viewed in the context of reports by those who understand the facts about Darwin's "conditions of life." They are energy-dependent and RNA-mediated

See for example: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition and Olfaction Warps Visual Time Perception

It has become obvious to all serious scientists that the sense of smell in bacteria must be linked from mRNA stability to our visual perception of mass and energy in the context of natural selection across the time-space continuum via the pheromone-controlled physiology of reproduction. The complexity of that fact may not be understood by biologically uninformed theorists, but no theorist should claim that the mechanisms of food energy-dependent pheromone-controlled biophysically constrained cell type differentiation are not understood by all serious scientists.

Avatar of: James V. Kohl

James V. Kohl

Posts: 525

Replied to a comment from Roy Niles made on August 29, 2017

August 30, 2017

"Adaptive mutation" is of course what we call the new self engineering procedure that many biological scientists have begun to accept - and we could just as well refer to that as "intelligent mutation" to boot.

Who is we? Please cite the literature that claims mutations are adaptive or intelligent. I suspect it has been published by biologically uninformed theorists, not those who write articles about patterns of epigenetic variation for "The Scientist."

Are you suggesting to the editors and readers of The Scientist that you know anything about how to link a pattern of random mutations from self engineering to biodiversity in species from microbes to humans?

Avatar of: James V. Kohl

James V. Kohl

Posts: 525

Replied to a comment from James V. Kohl made on August 30, 2017

August 30, 2017

Re: ...a strong link between population-specific DNA methylation, mRNA levels, and genotypes.


See also: Methylation Variation Documented Between Human Populations

"Our analysis of five worldwide populations revealed a strong correspondence between population-specific DNA methylation, messenger RNA levels, and genotypes," the authors wrote. "The correlation with genetic divergence was stronger for DNA methylation, and, consistent with this, our results suggest stronger local genetic control of population-specific DNA methylation levels than of mRNA expression levels."

The strong link and/or strong correspondence between food energy-dependent DNA methylation, messenger RNA levels and genotypes is biophysically constained by the pheromone-controlled physiology of reproduction in all livng genera. See for example: Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation”

The synthesis of RNA in isolated thymus nuclei is ATP dependent.

Glycolysis and the citric acid cycle appear to provide the free energy for nuclear ATP synthesis and the food-energy-depenent biosynthesis of messenger RNA. If so, all pathology is caused by the virus-driven degradation of messenger RNA, which links mutations but not from ecological variation to ecological adaptations.


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