Gene mutation to cope with modern diets may help protect against diabetes

A common gene variant, which evolved in response to cooking and farming, helps some people cope with modern diets by keeping blood sugar low.

However, new research on the gene reveals that close to half of the people studied still have an older variant that may be better suited to prehistoric diets and could make them more likely to develop type 2 diabetes.

The older version of this genetic variant likely would have been helpful to our ancestors as it would have helped maintain higher levels of blood sugar during periods of fasting. Dr Matteo Fumagalli

The newer gene variant became more common in humans after cooking and farming expanded, and might now help people avoid diabetes. This is according to research led by UCL and including an Imperial College London researcher, published today in eLife.

The study’s lead author Professor Frances Brodsky, director of UCL Biosciences, said: “We found that people differ in how efficiently their bodies can manage blood sugar levels, resulting from an evolutionary process that seems to have been brought about by changing diets.”

Transporting sugar

After we eat, the hormone insulin reacts to higher levels of blood glucose (sugars) by releasing a transporter, which removes glucose from the blood and stores it in muscle and fat tissue. Between meals, the glucose transporter is kept inside muscle and fat, so that it cannot remove glucose and some will continue to circulate in the blood.

The activity of the transporter is controlled by a protein called CHC22, controlled by a gene. A mutated version of this gene however creates a different variant of the protein CHC22.

The newer variant is less effective at keeping the glucose transporter inside muscle and fat between meals, meaning the transporter can more readily clear glucose out of the blood. People with the newer variant will therefore have lower blood sugar.

Diet shaping evolution

The team analysed human genomes, as well as those of 61 other species, to understand how the gene producing CHC22 has varied throughout evolutionary history.

In humans, by looking at the genomes of 2,504 people from the global 1000 Genomes Project, they found that almost half of the people had a variant of CHC22 that is produced by the mutated gene, which became more common as people developed cooking and farming. 

Understanding how we have adapted to these changes doesn’t only inform us about why people lived or died in the past, but also helps us to better understand the relationship between diet, health and disease today. Professor Mark Thomas UCL

The team also looked at genomes of ancient humans and found that the newer gene variant is more common in ancient and modern farming populations than in hunter-gatherers, suggesting that increased consumption of carbohydrates could have led to the genetic adaptation.

First author Dr Matteo Fumagalli, who began the study at UCL before moving to the Department of Life Sciences at Imperial, said: “The older version of this genetic variant likely would have been helpful to our ancestors as it would have helped maintain higher levels of blood sugar during periods of fasting, in times when we didn’t have such easy access to carbohydrates, and this would have helped us evolve our large brains.

“In more recent years, with our high-carb diets that often provide us too much sugar, the newer variant may be advantageous.”

Diet and disease today

The researchers say that while this genetic variant does not play a direct role in the development of diabetes, having the older variant may make people more likely to develop diabetes, and it may also exacerbate insulin resistance involved in diabetes.

Professor Brodsky said: “People with the older variant may need to be more careful of their carb intake, but more research is needed to understand how the genetic variant we found can impact our physiology.”

Co-author Professor Mark Thomas from UCL added: “Our analyses strongly suggest that we have found yet another example of how prehistoric changes in dietary habits have shaped human evolution.

“Understanding how we have adapted to these changes doesn’t only inform us about why people lived or died in the past, but also helps us to better understand the relationship between diet, health and disease today.”

The study was funded by the National Institutes of Health and the Medical Research Council.

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‘Genetic diversity of CHC22 clathrin impacts its function in glucose metabolism,’ by Matteo Fumagalli, Stephane M Camus, Yoan Diekmann, Alice Burke, Marine D Camus, Paul J Norman, Agnel Joseph, Laurent Abi-Rached, Andrea Benazzo, Rita Rasteiro, Iain Mathieson, Maya Topf, Peter Parham, Mark Thomas, & Frances M Brodsky is published in eLife.

Based on a press release by UCL.

Top image credit: Khritthithat Weerasirirut/Shutterstock