Text: Paule Goumaz
Photo: Cas Oorthuys/NFA, collectie Nederlands fotomuseum

DNA does not tell everything

Epigenetics suggests that our environment influences the heritable traits that we pass on to our children and grandchildren. Today, this field has opened up new possibilities in treating a number of diseases.

Towards the end of World War II, Nazi Germany enforced a blockade that left the populations of several Dutch provinces starving. The babies born to women who were pregnant during that “Hunger winter” were smaller than normal and in poor health. But surprisingly, their daughters and granddaughters also gave birth to sickly newborns who were more susceptible to developing Type 2 diabetes. In 2005, American researchers identified an epigenetic modification caused by DNA methylation in people exposed to the famine while in their mother’s womb. This change was then passed on to the following generation.

The sequencing of the first human genome in 2001 fuelled unprecedented progress but raised a number of questions. These issues can be summed up in the point made by geneticist Thomas Hunt Morgan (way) back in 1935: if an individual’s character is determined by genes, why aren’t all the cells in an organism identical? Our cells carry the same genes, but there is no resemblance whatsoever between muscle cells, liver cells or neurons.

Researchers only recently began digging more deeply into the field. “Epigenetics is the study of gene expression in the organism,” says Winship Herr, who teaches epigenetics at the Center for Integrative Genomics (CIG) at the University of Lausanne. “It addresses the idea that not everything is programmed in our DNA.”

The cells of our organism contain all our genes in their nucleus. But each individual cell only reads the genes it needs to build the proteins required for its function. In other words, some genes are activated and “expressed”, while others are silenced.

Whether or not genes are activated is determined by different chemical changes, which do not affect the DNA sequence.

Researchers believe that a number of environmental factors can cause epigenetic modifications, including nutrition – as shown in the study on the Dutch famine – the mother’s behaviour, stress and exposure to pollution.

Epigenetics first looks into embryonic development and cellular differentiation. “A well-known example is X chromosome inactivation in female mammals,” says Winship Herr. “This process, which occurs randomly in each cell, is normal in their development.”

But the phenomenon is associated with a number of diseases, especially metabolism disorders such as diabetes and obesity, auto-immune diseases and cancers. “Gene mutations and deregulation
in gene expression are at work in all cancers,” says Winship Herr. “We really hope to develop therapies that target these alterations and reprogramme cancer cells, i.e. initiate their differentiation and stop their uncontrolled growth.”

Researchers believe that a number of environmental factors can cause epigenetic modifications, including nutrition – as shown in the study on the Dutch famine – the mother’s behaviour, stress and exposure to pollution. “A growing number of diseases are influenced by these variations,” says Winship Herr. “But what about the transmission of this genetic information? Some changes will have to be passed on through several generations to be verified. Not even scientists agree completely on the very definition of epigenetics!”



​1. Epigenetics

In 1942, British biologist Conrad Waddington coined the term “epigenetic” to explain embryonic development. By epigenetic landscape, he referred to the processes whereby genes produce an individual’s observable characteristics (phenotype). Today, epigenetics refers to the study of changes affecting gene expression but

that do not cause mutations in the DNA sequence.

2. Phenotype

All of the observable characteristics (anatomical, morphological, molecular and physiological) of a living organism, determined by genes and the environment. For example, hydrangea of the same genetic variety can have a colour (phenotype) ranging from pink to blue depending on soil acidity.

3. Methylation

One of the best known biochemical modifications in gene expression. In this process, methyl groups (made up of carbon and hydrogen atoms) are added to the DNA and either activate or suppress the function of certain genes.

4. Chromatin

The structure likened to “beads-on-a-string”, whose main function was long believed to be to compact DNA – which is two metres long! – into the cell nucleus. Chromatin also plays an essential role as it promotes gene accessibility and expression, depending on whether the genes are “turned on” or “turned off”.