Ancient gene mutation could protect against diabetes, study finds
An ancient mutation that spread through humans after the advent of cooking may protect people against high blood sugar and diabetes today, scientists have said.
Researchers at University College London (UCL) discovered the mutation while studying a gene called CLTCL1, which is heavily involved in removing sugar from the bloodstream.
While a certain amount of blood sugar is necessary to provide energy to the brain and other organs, too much leads to type 2 diabetes, where the body loses its ability to control how much sugar is circulating.
The scientists found that about half the world’s population carries a mutation that helps the body to clear sugar from the circulation more effectively than in the past.
The scientists believe the mutant form of the gene became common when humans turned to cooking nearly half a million years ago, though it may
be a more recent event that took off with farming about 12,500 years ago.
“Cooking and farming meant more sugar in the diet, so we needed to clear it more readily,” said Prof Frances Brodsky, a biochemist who led the research. “This is an example of evolution in action which influences human metabolism and vice versa.”
By comparing the DNA of humans and various other species, the scientists traced the CLTCL1 gene back nearly 500m years to when the first jawed vertebrates evolved. Since then, several species have lost the gene, including mice, sheep and pigs, suggesting it is not important for all organisms.
But writing in the journal eLife, the scientists describe how humans not only retain the gene but carry different forms of it, with the mutant variant becoming popular only after cooking and farming became widespread.
Matteo Fumagalli, the first author on the study, said that with modern high-carbohydrate diets, the mutant form of the gene “may be advantageous”. When we eat carbohydrate, it is turned into sugar that circulates in the blood to provide energy, or is stored as fat.
After a meal, the body responds to the rise in blood sugar by opening little pores in the membranes of muscle and fat tissue to allow the sugar in. These holes are created by “glucose transporters” which, between meals, are held inside the tissues by a protein made using the CLTCL1 gene.
In the ancient past, the older form of the gene was useful for early humans because the protein it made held glucose transporters firmly inside muscle and fat, meaning blood sugar levels stayed high. This would have been particularly useful while humans were growing their large and complex brains, Brodsky said.
But the arrival of cooking and farming meant humans gradually had more sugar in their diet. This favoured the newer mutation which encodes a protein that is less effective at keeping glucose transporters tucked away inside muscle and fat. As a result, more sugar flows into the tissues and glucose levels in the blood fall.
“We know from tests on cells that the newer variant leads to more sugar clearance than the older one,” said Brodsky. “There’s a measurable effect.”
Brodsky said knowing which gene variant people carry could help them understand their risk of type 2 diabetes. Those with one or two copies of the older form may need to watch their carbohydrate intake more and may be more likely to develop diabetes.
• This article was amended on 4 June 2019 to make clear that the research relates to type 2 diabetes.