Antidiabetic mutation
Scientists have found out why civilization has not turned all people into diabetics
Boiled food and sugary drinks have not yet turned all of humanity into diabetics thanks to a mutation in the CLTCL1 gene, which allows the body to quickly burn excess glucose in muscles or store it in adipose tissue. This conclusion was reached by geneticists who published an article in the journal eLife (Fumagalli et al., Genetic diversity of CHC22 clathrin impacts its function in glucose metabolism).
"The old version of this gene was useful to our ancestors, as it helped to maintain high blood sugar levels during fasting. At that time, people did not have constant access to carbohydrates, and this ability could help the development of a large brain. Now there is no need for this," says Matteo Fumagalli from Imperial College London (in a press release Gene mutation evolved to cope with modern high-sugar diets – VM).
In recent years, scientists have found more and more evidence that the cultural evolution of man, the invention of new methods of extraction and processing of food significantly influenced the structure of DNA and the spread of certain traits among the populations of ancient people.
For example, the first farmers had a unique mutation in the LCT gene that allowed adults to drink milk – an ability that almost all mammals lose in childhood. Even earlier, people acquired a new version of the AhR gene, which Neanderthals did not have – it helps the lungs to carry smoke from bonfires more easily.
Interestingly, similar processes affected not only people, but also the animals they tamed. Five years ago, geneticists discovered that dogs, unlike wolves, learned to digest starch and other carbohydrates – there were a lot of them in the food that the first owners shared with them during domestication.
Fumagalli and his colleagues, who studied the history of the appearance of the CHC22 protein and the CLTCL1 gene associated with it, found another interesting example of how cultural and technological progress influenced human biological evolution.
CHC22 and CLTCL1 play an important but indirect role in the regulation of glucose levels in the body. With an excess of insulin in the blood, CHC22 molecules help another enzyme, GLUT4, reach the cell surface and begin capturing and transporting sugar molecules. When the sugar concentration drops, CHC22 turns off, and muscles and adipose tissue stop burning glucose.
Some animals, including mice, lost CHC22 during evolution, which made Fumagalli and his colleagues think about how rodents regulate glucose levels.
As a result, scientists analyzed and compared the structure of this part of DNA in about six dozen vertebrates and invertebrates. As it turned out, this gene changed quite often as it evolved.
In some cases, animals lost it, as happened with rats and mice or with the blind diabetic fish Astyanax mexicanus. In other cases, for example, in songbirds-amadine and Amazonian fish-pecilia, the number of its copies doubled. At the same time, the CLTC gene (another part of the DNA associated with glucose metabolism) in all animals almost did not differ in structure.
All this indicated that CLTCL1 is not necessary for survival, and changes in its structure and the number of copies simply reflect the conditions in which a particular creature lives. Then scientists made a comparison for two thousand modern humans and the genomes of ancient Cro-Magnons, Neanderthals and Denisovans.
Like animals, all modern and ancient humans had the same CLTC structure, but CLTCL1 had two different forms. Primates and ancient representatives of the genus Homo, as well as hunter-gatherers, had only one version of this gene – M1316, whereas modern humans, especially civilized peoples, were characterized by another variation – V1316.
Having discovered these differences, scientists traced how the appearance of a typo in DNA affects the metabolism of sugars. It turned out that the replacement of just one amino acid in CLTCL1 led to the fact that this protein became more actively involved in glucose transport and less responsive to insulin signals.
According to Fumagalli, the appearance of this mutation among the first farmers suggests that such a change in the work of metabolism helped our ancestors to adapt to food with a large amount of easily digestible carbohydrates. The same feature of modern people explains why not all of them suffer from diabetes, despite the huge amount of sugar in almost all products.
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