The new study, published in Genome Biology, reports that while a child's genes are inherited directly from their parents, how these genes are expressed is controlled through 'epigenetic' modifications to the DNA which are controlled by a mothers environment before conception – warning that diet is likely to play a role in this process.
An international collaboration led by researchers at the Medical Research Council (MRC) Unit, based in The Gambia, the MRC International Nutrition Group at the London School of Hygiene & Tropical Medicine and Baylor College of Medicine in Houston, reported on from a unique ‘experiment of nature’ where the population's dependence on own grown foods and a markedly seasonal climate impose large differences in diet and other environmental factors between rainy ('hungry') and dry ('harvest') seasons.
"By studying babies conceived to mothers eating very different diets in the dry and rainy seasons in rural Gambia we could exploit a natural experiment,” said study first author Dr Matt Silver.
The teams independently identified a single gene as the key to driving changes in differences expressed between the groups: “Our results show that the methylation marks that regulate how VTRNA2-1 is expressed are influenced by the season in which babies are conceived,” he added.
Indeed, the team noted that because methylation requires a defined set of nutrients, a mother's nutrition before and during pregnancy can affect the 'setting' of these tags, with potentially permanent consequences for her child's gene function.
“Maternal nutrition is the most likely driver,” said Silver.
Professor Andrew Prentice, who leads the MRC Unit in The Gambia and the MRC International Nutrition Group in London said the team believes their data “is the first concrete evidence that a mother's diet before pregnancy can affect the disease risk of her child by rewriting a tiny portion of its epigenome.”
"Because this gene plays a key role in controlling response to viral infections and offering protection against certain cancers, the potential implications are enormous.”
Needle in the haystack
Two research team teams took complementary and independent approaches to investigate new areas of genes that differ in their level of methylation (known as metastable epialleles) in the human genome. Remarkably, both zeroed in on the same top hit: the VTRNA2-1 gene.
"There are around 20,000 genes in the human genome. So, for our two groups, taking different approaches, to identify this same gene as the top epiallele was like both of us digging into different sides of a gigantic haystack and finding the exact same needle,” said Professor Rob Waterland of Baylor, who led the US arm of the study.
The team enrolled 120 pregnant women who conceived at the peak of either the rainy or dry season and measured the concentrations of nutrients in their blood.
They later analysed blood and hair follicle samples from their 2-8 month old infants.
"Our next step is to follow Gambian children to test exactly how epigenetic differences in the VTRNA2-1 gene affect gene expression and life-long health,” said Prentice.
“This could help shed light on longstanding questions such as why mortality rates due to infection are higher in Gambians born in the rainy season."
Source: Genome Biology
Volume 16, Number 118, doi: 10.1186/s13059-015-0660-y
"Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment"
Authors: Matt J Silver, et al