Between 1944 and 1945 during World War 2, the western part of the Netherlands experienced a winter famine. In the following decades, it became evident that the offspring of people who were in utero during the famine displayed a range of distinct physical attributes (or phenotypes) that could be directly linked to the famine. These included obesity, cardiovascular problems and diabetes.

However, no direct genetic changes were detected in the offspring. So how were these inherited phenotypes being passed on to the next generation?

It’s not just what the DNA says…..

The Dutch Winter Famine was a direct example that environment could have an impact on the genome without directly altering the DNA sequence. But how is this possible? It’s from a phenomenon called epigenetics. An epigenetic change is a change in gene activity (termed gene expression), rather than a change to the sequence.

It’s how you look…

A DNA sequence consists of combinations of 4 molecules called cytosine, guanine, adenine and thymine. Now, if anyone remembers the animation in ‘Jurassic Park’, these combinations form a blue print for an organism. The basic structure of a gene includes a region where proteins can bind and influence the gene expression by either allowing the expression to occur or by stopping it.

These regions often contain stretches cytosine and guanine sitting next to each other. When this occurs, a chemical modification to cytosine can occur. This modification, called methylation, changes the structure of DNA from being ‘open’ to being ‘closed’. This means that the proteins that bind to influence the expression of the gene can no longer bind, and the gene is “switched off”. Thereby changing the gene expression without changing the sequence.

But let’s remember the famine.

So how does DNA methylation relate to the Dutch Winter Famine? It has now been demonstrated that DNA methylation is very sensitive to environmental changes, is long-lasting and can be inherited. It is also known that much of the DNA methylation changes that occur, happen at a particular time point during gestation.

Studies have since shown that maternal diet can alter the epigenetics of offspring during gestation, and that these changes can be transgenerational, like the effects of the Dutch Winter Famine. Further studies of the offspring of individuals exposed to the famine in utero, have demonstrated that the offspring of exposed males have higher rates of obesity and a greater BMI.

You are the sum of many things.

Epigenetic control of gene expression involves many other players besides DNA methylation, but both the DNA sequence and the epigenetic factors interact to create differences between genetically similar organisms. Think of twins who are identical but display many differences. This is epigenetics in a nutshell.

Food for thought.

A final thought: what you eat today could have repercussions for several generations, not just your waistline!








3 thoughts on “Epigenetics

  1. I wonder whether the same or a similar effect occurs in children born before the Famine (p e in 1941), but experienced the famine later, in 1944/45?


    1. Given what we know, yes there would be effects on children already born. But the interesting thing about the children exposed in Utero is that it was basically the largest controlled study where the children had not been exposed to other environmental influences that children already alive had been exposed to and need to be taken into account!


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