https://elifesciences.org/articles/41517 [open access]
eLife 2019;8:e41517
DOI: 10.7554/eLife.41517
The Science Daily interpretation "Gene mutation evolved to cope with modern high-sugar diets" is here:
https://www.sciencedaily.com/releases/2 ... 084857.htm
I wasn't able to find the CLTCL1 variant information in my genetic reports.
Abstract & Digest from eLife paper:
Abstract
CHC22 clathrin plays a key role in intracellular membrane traffic of the insulin-responsive glucose transporter GLUT4 in humans. We performed population genetic and phylogenetic analyses of the CHC22-encoding CLTCL1 gene, revealing independent gene loss in at least two vertebrate lineages, after arising from gene duplication. All vertebrates retained the paralogous CLTC gene encoding CHC17 clathrin, which mediates endocytosis. For vertebrates retaining CLTCL1, strong evidence for purifying selection supports CHC22 functionality. All human populations maintained two high frequency CLTCL1 allelic variants, encoding either methionine or valine at position 1316. Functional studies indicated that CHC22-V1316, which is more frequent in farming populations than in hunter-gatherers, has different cellular dynamics than M1316-CHC22 and is less effective at controlling GLUT4 membrane traffic, altering its insulin-regulated response. These analyses suggest that ancestral human dietary change influenced selection of allotypes that affect CHC22’s role in metabolism and have potential to differentially influence the human insulin response.
eLife digest
When we eat carbohydrates, they are digested into sugars that circulate in the blood to provide energy for the brain and other parts of the body. But too much blood sugar can be poisonous. The body regulates blood sugar balance using the hormone insulin, which triggers the removal of sugar from the blood into muscle and fat cells. This removal process involves a pore in membranes at the surface of muscle and fat tissue, called a glucose transporter, through which the sugar molecules can pass. During fasting, the glucose transporter remains inside muscle and fat. But after a meal, insulin acts to release the transporter from its storage area to the surface of the tissue. How efficiently this process happens reflects how efficiently sugar can be removed from the blood. When this pathway breaks down, it can lead to diabetes.
In humans, a protein called CHC22 is needed to deliver the glucose transporter to its storage area. In mice, CHC22 is absent. The question arises: do different animals' eating habits influence CHC22's role in controlling blood sugar? The evolutionary history of CHC22 in a number of different animals could reveal what is special about glucose transport after a meal in humans, and how it might fail in diabetes.
By analyzing the genomes of several different species, Fumagalli et al. found that the gene encoding CHC22 first evolved around the time animals began developing a backbone and complex nervous systems. Afterwards, it was lost by some animals – including mice, sheep and pigs. Fumagalli et al. also discovered that CHC22 varies between individual people. A new form of CHC22, which first appeared in ancient humans, is less effective at holding the glucose transporter inside muscle and fat – leading to a tendency to reduce blood sugar levels. This new form became more common in humans over a period witnessing the introduction of cooking, and later farming; both of these technologies are associated with increased sugar in the diet. But not everyone has this new variant of the gene – both the old and newer variants are present in people today.
The history of CHC22 suggests that it was useful for early humans to hold the glucose transporter inside muscle and fat, keeping blood sugar levels high, which contributed to the development of a large brain. But as humans became exposed to higher dietary levels of sugar the newer form of CHC22 allowed blood sugar to be lowered more readily. People with different forms of CHC22 are likely to differ in their ability to control blood sugar after a meal. In some cases, this could lead to heightened blood sugar levels, which in turn can lead to diabetes.
