Do we inherit more than just our genes?

06 November 2018

Non-genetic traits inherited between generations are rarer than previously thought, according to a new study in Cell

Scientists have observed that certain traits, like susceptibility to depression or obesity, can be passed down through generations without being directly linked to an individual’s DNA code. This could have far reaching consequences, as it might suggest that a person’s diet or lifestyle, even years before they have children, may affect the mental or physical health of their future family.

This non-genetic inheritance is thought to be caused by epigenetic marks attached to the DNA. “I like to think of epigenetics as the punctuation of DNA”, said Tessa Bertozzi, a PhD candidate at the University of Cambridge’s Department of Genetics. Many of these “punctuation” or epigenetic marks are absolutely necessary for the normal function of cells, but some can be acquired or changed throughout life. For example, severe undernutrition in childhood can alter a person’s epigenetic marks so they are more susceptible to diabetes.

There is evidence that epigenetic marks acquired throughout life can be passed down to future generations in a phenomenon called epigenetic inheritance. This is a scary thought, as it would mean that even if a mother eats healthily during her pregnancy, a period of undernutrition from her childhood could still lead to health problems for her children or even grandchildren.

However, “[epigenetic inheritance] is incredibly hard to study in humans, for ethical reasons but also because of the incredible genetic diversity that we see in human populations”, said Tessa. This is why many labs interested in epigenetic inheritance will use mouse strains bred to be genetically identical. 

A team led by Professor Anne Ferguson-Smith at the University of Cambridge were interested in studying how common epigenetic inheritance might be. They were focused on discovering if there were other genes in the DNA of a mouse that behaved like the agouti gene in a specific mouse mutant called agouti viable yellow. In agouti viable yellow mice, the agouti gene controls coat colour depending on what epigenetic marks are nearby. Mice with the normal number of epigenetic marks near the agouti gene have brown fur, but mice with fewer marks have yellow fur - despite the yellow and brown mice having exactly the same genetic code.

The team scoured the mouse genome for regions of DNA that show the same variable patterns of epigenetic marks that the agouti gene does. They settled on 6 regions, and found that only one region showed evidence of epigenetic inheritance in the next generation. Even in that one region, the effect of the inheritance was very small and only inherited from the mother - not the father. So although the team was hoping to find other genes that could be used to study epigenetic inheritance, like agouti, they showed instead that the behaviour of the agouti gene may be more anomalous than routine.

“I think our study really challenges how wide-spread this phenomenon is, and makes us question the weight we put on some of these isolated examples” said Tessa. Importantly, it suggests that maintaining acquired epigenetic marks into the next generation is likely to be a quirk of the agouti gene, rather than a common trait of lots of different genes. So, for now, it seems like the mechanism behind non-genetic inheritance is still something of a mystery.

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