Traces of Dutch 'Hunger Winter' in genetic material
Conditions in the uterus can give rise to life-long changes in genetic material. People in their sixties who were conceived during the Hunger Winter of 1944-45 in the Netherlands have been found to have a different molecular setting for a gene which influences growth. Researchers from the LUMC are the first to demonstrate this effect. They published their findings this week in PNAS Online Early Edition, together with colleagues from Columbia University.
During the Hunger Winter (the Dutch famine of 1944-1945) the west of the Netherlands suffered from an extreme lack of food. It now appears that the limited food intake of mothers who were pregnant during this period altered the genetic material of embryos in the early stages of development. The effects of this can still be observed some sixty years later. These alterations are not changes in the genetic code, but a different setting for the code which indicates whether a gene is on or off. This is known as epigenetics. One of the main processes in epigenetics is connecting the small molecule methyl to DNA.
The researchers compared the degree of methylation of a piece of DNA, the IGF2 gene, of people who were conceived in the Hunger Winter with that of their brothers and sisters. They chose this particular gene because it plays an important role during gestation. People in their sixties who were conceived during the Hunger Winter have less methyl groups on the IGF2 gene than their siblings. This did not apply to children of the Hunger Winter who were in later stages of gestation when the famine occurred. They did have a lower birth weight than their siblings, but the IGF2 gene was not 'packaged' differently. This indicates that epigenetic information is particularly vulnerable in the early stages of pregnancy.
‘The next question is whether the epigenetic change which has been identified is a 'scar' on the DNA because of lack of food, or a specific adaptation to the shortage of food,' comments Prof Eline Slagboom. Researcher Dr Bas Heijmans: ‘Epigenetics could be a mechanism which allows an individual to adapt rapidly to changed circumstances. Changes in the DNA sequence occur by chance and it takes generations before a favourable mutation spreads throughout the population. By then, a temporary famine is long past. It could be that the metabolism of children of the Hunger Winter has been set at a more economical level, driven by epigenetic changes.' This could explain why children of the Hunger Winter suffer more frequently from obesity and cardio-vascular diseases. The research was partly financed by the Netherlands Heart Foundation and the EU network LifeSpan.