If variety is the spice of life, then DNA methylation sure seems to be supplying some of the flavor. A new study shows that DNA methylation isn’t just responsible for the differences in individuals, but for variations in populations as well. We’re no strangers to the way that DNA methylation can differ in diseases and cell types, or even between twins, but while lots of research has been focused on the potential for variation at the cellular level, relatively little has looked at how epigenetic variation affects humans at the population level.

In their Genome Research paper, scientists lead by Dr. Manel Esteller, from the Bellvitge Biomedical Research Institute (IDIBELL) in Barcelona and others at the Mayo Clinic, touched on some fundamental questions: Can epigenetic modifications drive evolution? Can they explain some of the differences between diverse human populations? Does evolutionary theory need to take the 100’s of possible epigenetic modifications (and their combinations) into account and stop focusing on just 4 base pairs? Can epigenetic differences explain the missing heritability troubling GWAS?

To search for answers, the talented group “generated genome-scale DNA methylation profiles of three human populations (Caucasian-American, African-American, and Han Chinese-American) and examined the differentially methylated CpG sites.” Here’s what they found:

Populations have genes with distinct methylation profiles.

“Population specific CpGs are associated with histone modifications and transcription factor binding that actively regulate gene expression, suggesting a regulatory network that contributes to the variance observed between populations.”

These genes are associated with immune response and disease (Diabetes, Parkinson’s, HIV…) and responses to environmental agents, like drugs.

There are two types of epigenetic inheritance (at the population level):

Genotype Dependent: Most of the DNA methylation differences were traced backed to genetic variation, “suggesting the evolutionarily set genetic context influences DNA methylation, which subsequently functions as an intermediate regulatory event mediating phenotypic differences between populations.” Genotype Independent: Interestingly, 1/3rd of the variation in DNA methylation could not be traced back to genetic variation, “suggesting that variation in population-specific sites takes place at the genetic and epigenetic levels.”

When it comes down to the take home message, this research helps to establish “the contribution of epigenetic modification to natural human variation.” Ultimately, it appears that the modern synthesis of evolutionary theory needs to learn a thing-or-two about epigenetics.

While evolution is busy playing catch-up, get a head start at Genome Research, 2013