Epigenetic mechanisms as an archive of ancestral dietary history of populations: The premise, proposal and pilot

Epigenetic mechanisms have been widely studied for the past several decades, yet despite a surfeit of literature examining animal models and extensive human research associating these mechanisms with pathology, little is known regarding the normal variation among populations or the phenotypic relevance of that variation. Moreover, no one is certain of the evolutionary significance these mechanisms and their underlying machinery. Their structure and function are highly dependent upon dietary intake of indispensable nutrients, yet nutrient profiles vary across populations and generations in an ongoing manner and energy intake can fluctuate dramatically. Here, we examine how the DNA methylation might archive ancestral dietary patterns and discuss the initial findings in a pilot study on population variation in DNA methylation patterns in four maternal/offspring duos from three continents (n = 88). This pilot examined DNA methylation patterns across the core promoter of the metabolic gene leptin (LEP), a leading regulator of energy homeostasis and adipogenesis. Remarkably similar overall mean patterns were present across 7 CpG sites which include the C/EBPα transcription binding site, and two sites proximal to the TATA. Findings suggest a stable and conserved DNA methylation pattern in this region of the (LEP) promoter across populations consuming diets from varying food chains.