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Old Sat, Dec-08-18, 03:01
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nawchem nawchem is offline
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Default The deep roots of diabetes

https://evolution.berkeley.edu/evol...140204_diabetes

Excerpt: Last month, scientists announced that they'd discovered a gene that helps explain the difference in diabetes risk among many populations. In a strange twist, the gene version in question traces its ancestry back to Neanderthals! What exactly is going on here?

Where's the evolution?
To understand the evolutionary back story, you first need to know a little about the gene itself. The gene in question encodes a protein that helps move certain lipids into liver cells. The diabetes-contributing version of this gene differs from the standard gene version by five mutations—and these seem to alter the function of the protein enough to increase diabetes risk. Carriers of the mutated version of the gene are more likely to get diabetes at a younger age and with a lower degree of obesity than non-carriers.

Anyone can carry this gene—but the new research found that it is more common in some populations than others. Among people with many Native American ancestors, the likelihood of carrying at least one copy of the mutated gene is greater than 50%. Among East Asians, the frequency is about 10%. Among people with mainly European ancestors, the gene version is extremely rare, and it seems to be not present at all in Africans. Because people from Mexico and Latin America are much more likely to have Native American ancestry, they are also much more likely to carry this gene version, and hence, have higher odds of developing diabetes.

Through recent advances in recovering DNA from ancient bones, the genomes of several Neanderthal individuals have been reconstructed. The researchers searched through the DNA sequences of these samples and found what they were looking for. One of the Neanderthals (a newer fossil discovery from Denisova Cave) carried the diabetes-linked sequence! It seems that this gene version, now common among people of Native American ancestry, is a relic from the period of our history when humans walked the earth alongside other hominids.

This discovery does not mean that people of Native American descent (or for that matter anyone who carries the diabetes gene version) are particularly closely related to Neanderthals. Human populations from all over the world seem to have similar degrees of Neanderthal ancestry (between 1 and 4%); we all just carry different subsets of Neanderthal-derived genes—that is, unless your ancestors are from sub-Saharan Africa, where many people have no Neanderthal ancestry at all.

Neither does this discovery mean that Neanderthals had diabetes. Type 2 diabetes is a disease of the modern world, borne of a mismatch between modern, unhealthy lifestyles and a metabolism that, for the vast majority of our evolutionary history, existed in an environment where food was relatively scarce and lots of physical activity was necessary to survive. In that harsh environment, even individuals carrying genes that contribute to diabetes when food is plentiful and sedentary lifestyles are common are unlikely to develop diabetes. This helps explain how such genes can be common today. At no point in our evolutionary history have they been exposed to the rigors of natural selection. Only recently have such genes become detrimental to human health!

This discovery highlights the importance of evolutionary history in understanding and improving human health. Even the deepest roots of our past, which lead back to Africa and to our common ancestors with other, now-extinct hominid species, may become relevant at your next doctor's appointment. And we are just beginning to understand these ramifications. Advances in DNA technology have only recently allowed us to study the intersections between ancient DNA, large-scale genomic data, and modern epidemiology. So stay tuned to learn more about the results of these exciting investigations!
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Old Sat, Dec-08-18, 03:47
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nawchem nawchem is offline
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https://www.livescience.com/42278-n...2-diabetes.html

The research team, known as the Slim Initiative in Genomic Medicine for the Americas (SIGMA) Type 2 Diabetes Consortium, performed the largest and most comprehensive genetic study to date of Type 2 diabetes in Mexican and Mexican-American populations. This involved analyzing the genomes of more than 8,200 Mexicans and other Latin Americans, including more than 3,800 people with Type 2 diabetes and more than 4,300 without the condition.

The investigators discovered a risk gene for Type 2 diabetes known as SLC16A11 that had gone undetected in previous research. People who carry the higher-risk mutation of the gene, which is active in the liver, are 25 percent more likely to have diabetes than those who lack the mutation, and people who inherited copies of this gene variant from both parents are 50 percent more likely to have diabetes.

The higher-risk version of this gene is seen in up to half of people who have recent Native American ancestry, including Latin Americans. The fact that this gene mutation is more common in Latin Americans could account for as much as 20 percent of their increased levels of Type 2 diabetes.

The researchers noted changing levels of the protein that the gene encodes could alter the amount of a specific type of fat, one that prior studies have linked to the risk of diabetes.

"What is most exciting to me, and has the greatest long-term implication, is a new clue about the biology of Type 2 diabetes,"study co-authorDavid Altshuler, professor of genetics and medicine at Massachusetts General Hospital and the Broad Institute, told LiveScience.

"If we can come to understand the biological function of SLC16A11, and how changing its sequence increases risk of Type 2 diabetes, then we may in the long run be able to develop improved prevention or treatment," Altshuler added.

Roots of diabetes

Although this gene variant is common among people with recent Native American ancestry and is also found in about 20 percent of East Asians, only 2 percent of Europeans have it, and no known Africans carry SLC16A11. This pattern is somewhat unusual; modern humans arose in Africa, so nearly all common human genetic variants are found in African populations. [Top 10 Mysteries of the First Humans]

To uncover the roots of this odd pattern, the researchers investigated ancient human DNA and found the high-risk mutation of this gene was apparently inherited from Neanderthals, the closest extinct relatives of modern humans. Recent analysis of Neanderthal DNA revealed the ancestors of modern humans interbred with Neanderthals; the first high-quality genome sequence from a Neanderthal suggests about 1.5 percent to 2.1 percent of the DNA of modern humans living outside Africa is Neanderthal in origin. In contrast, Neanderthal DNA is much less common among modern Africans, matching these latest findings.

The scientists are now using their findings "to design new studies that aim to understand how this variant influences metabolism and disease," study co-authorTeresa Tusie-Luna, principal investigator at the National University of Mexico's Biomedical Research Institute, said in a statement.

These insights could "illuminate new pathways to target with drugs and a deeper understanding of the disease," study co-author José Florez, from the Broad Institute and Harvard Medical School, said in a statement.

The researchers cautioned that Type 2 diabetes is a complex disease influenced by multiple genes and by environment and behavior. "Our finding is only one piece in a large and complex puzzle," Altshuler said. "Any clinical translation of this finding will take many years. It is still in the research phase, and any health benefits will take time."

The scientists detailed their findings online Dec. 25 in the journal Nature.

Last edited by nawchem : Sat, Dec-08-18 at 03:57.
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Old Sat, Dec-08-18, 03:53
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nawchem nawchem is offline
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Plan: No gluten, CAD
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Voight, B. F. et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nature Genet. 42, 579–589 (2010)
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