[LUM#8] The Hidden Life of Our Genes
While genetics is the study of genes, epigenetics focuses on how those genes are expressed. It is a promising field that opens up new horizons for medical research.
In 2001, a kitten unlike any other made headlines around the world. Its name: Carbon Copy. What made it special? This little ball of fur is a clone. It has exactly the same genetic makeup as the mother cat from which it was born. Yet there’s one characteristic that isn’t immediately obvious: although the two cats have exactly the same DNA, they don’t have the same coat. How can two clones, carrying the same genes, be so different? “Heredity isn’t limited to our genes alone, because DNA doesn’t carry all the information,” explains Giacomo Cavalli. That is the key to this surprising difference in fur: epigenetics.
Epigenetics is the study of changes in gene activity that are not linked to alterations in the DNA sequence.“Gene function depends not only on the primary sequence but also on a number of modifications to the chromosome,” explains the researcher from the Institute of Human Genetics (IGH). These modifications correspond to biochemical marks placed by specialized enzymes on DNA or on proteins called histones, which are responsible for compacting DNA so that it can fit inside the cell nucleus. The same genome can therefore be expressed differently depending on epigenetic modifications (see box).
The same but different
While these changes play a major role in embryonic development, they also occur throughout life, particularly under the influence of the environment: what we eat, what we drink, and the products we are exposed to trigger epigenetic changes that affect our biology… and perhaps also that of our offspring. “Epigenetics is a mechanism of inheritance that complements genetic inheritance,” explains Frédéric Bantignies of the IGH.
The two researchers thus discovered a new mechanism of epigenetic inheritance in Drosophila. By modifying the structure of the chromosomes at the level of the genes that produce eye pigments, they obtained flies with exactly the same DNA, but with varying eye colors. They then observed the offspring of these fruit flies and found that this change in eye color was passed on to their offspring.
Are the epigenetic changes we carry also passed on to our children and grandchildren? This is what some population-based observational studies suggest, such as the “Dutch Mothers” study, which followed a group of pregnant women exposed to famine during World War II. Due to malnutrition, these women gave birth to low-birth-weight babies. Once the famine ended, these children grew up with a normal diet; yet when they had children of their own, they gave birth to low-birth-weight babies. “The effects of malnutrition on these women were passed on to their grandchildren even though they do not affect the DNA sequence; these are therefore epigenetic changes,” explains Giacomo Cavalli.
Therapeutic hope
“ Are we, in that case, shaped by our grandparents’ behaviors and the epigenetic changes induced by their environment? ” “In reality, it seems that very few of these epigenetic changes are passed down through the generations, and we don’t yet know how,” replies Frédéric Bantignies.“This is an entire area of the mechanisms of inheritance that remains unknown,” adds Giacomo Cavalli.
This also opens up new avenues for a whole field of medical research.“Epigenetic changes play a role in the development of certain diseases such as obesity, diabetes, or cancer,”the researchers explain. Unlike phenomena that affect the genome, these epigenetic variations can be “erased” by chemical treatments, offering hope for new therapies.“There are already epigenetic drugs being tested to treat certain cancers,”the researchers note. These epigenetic drugs may one day enable us to treat diseases against which we are currently powerless.
At the heart of our cells
Every cell in our body contains our entire genetic makeup within its nucleus: 46 chromosomes containing approximately 25,000 genes. A gene is a segment of DNA that contains the information necessary for the synthesis of the molecules that make up the organism. But for this synthesis to occur, the gene must be readable. This is where epigenetic modifications come into play: by placing biochemical marks on the DNA, they can alter the gene’s readability and thus modify its expression. This is notably what explains why all the cells in our body—which all have the same genome—are not identical. A skin cell thus differs from a neuron, which itself does not have the same functions as a heart cell, even though they share exactly the same DNA.
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