Is evolution pushing our DNA towards diabetes?

Illustration for article titled Is evolution pushing our DNA towards diabetes?

Eighty DNA variants associated with type-1 diabetes have undergone positive selection, increasing in prevalence over recent generations. Here's the crazy part - 58 of those variantsincrease the risk of the deadly disease. Why is evolution seemingly out to get us?

The answer, of course, is that evolution can't be out to get us - by definition, positive selection of genes and traits works to maximize our species's chance of survival. So something about those particular DNA combinations that increase the risk of type-1 diabetes must also be conferring some positive benefit that outweighs the dangers of diabetes.

Of course, it would have to be a pretty big benefit. Type-1 diabetes, also known as juvenile diabetes, primarily affects children by causing a potentially lethal shortage of insulin in their bodies. The fact that it affects people who haven't yet reached reproductive age is crucial - natural selection should pretty much always select against diseases that can kill people before they get a chance to pass on their genes. (On the other hand, there wouldn't be nearly as much evolutionary pressure on the more common type-2 diabetes, which mostly affects post-reproductive adults.)


Lead researcher Atul Butte, a biologist at Stanford medical school, explains the conundrum:

"At first we were completely shocked because, without insulin treatment, type-1 diabetes will kill you as a child. Everything we've been taught about evolution would indicate that we should be evolving away from developing it. But instead, we've been evolving toward it. Why would we have a genetic variant that predisposes us to a deadly condition?"

The best answer is that the genetic variants that increase the diabetes risk are also decreasing the risk of certain viral or bacterial infection. That would have made particular sense in a past where infectious diseases ran rampant, and the risks of dying young from these mostly untreatable illnesses far outstripped the dangers of diabetes. It's not yet clear whether the same mutated genes that increase the diabetes risk also provide this protection, or if it's neighboring genes whose allocation from generation to generation is intertwined with the diabetes gene.

Maybe the best example of this genetic phenomenon is seen with the disease sickle cell anemia. A particular recessive gene causes the painful, potentially deadly disease if both parents pass it along to their offspring. It's the sort of trait that natural selection would have weeded out if not for the fact that people with only a single copy of the gene have increased protection against malaria. As such, the sickle cell gene is a net positive, because more people are protected from malaria than become sickle cell patients. (Although that evolutionary balance might shift if we ever managed to wipe out malaria.)


The diabetes question is more complex than the sickle-cell anemia case because it's not limited to the mutation of a single gene. Complex diseases like diabetes are tied to a number of DNA variants, or locations where the nucleotide combinations vary between different people. These variants are known as single nucleotide polymorphisms, or SNPs for short. You can calculate a person's susceptibility to a particular disease by figuring out the net effect of his or her variants, which will likely be a mix of beneficial, malicious, and neutral.


Genome studies have revealed several hundred variants that can play a role in diabetes, so it's supremely complicated to figure out the precise interplay of all these different strands of DNA. Still, the raw numbers are striking - of the 80 DNA variants that have increased in prevalence, only 22 increase protection while 58 cause greater risk of developing the disorder.

There are some possible candidates for the diseases these variants are protecting against. For instance, the gene IFIH1 has been found to increase diabetes risk while also protecting against enterovirus infection, which can cause severe, possibly lethal, abdominal pains. Another disease the researchers found had a majority of increasing risk factors, rheumatoid arthritis, has had its less protective gene variants linked to a sharp decrease in tuberculosis risk.


Still, the picture is far from complete, and Butte and his team are going to keep testing more and more SNPs until they can figure out why natural selection keeps favoring a greater risk of diabetes over the alternative. Until then, Butte says it's a mystery with only the sketchiest answers available:

"It's possible that, in areas of the world where associated triggers for some of these complex conditions are lacking, carriers would experience only the protective effect against some types of infectious disease. Even though we've been finding more and more genetic contributions to disease risk, that's not really an appealing answer. There have got to be some other reasons why we have these conditions."



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.....I can't believe the title of this article...Almost all diabetics bring it upon themselves via poor diet. Type 1 is a rare form of diabetes, especially in America. In some parts of the world, diabetes is nearly unheard of.

If everyone was getting type 1 diabetes, I would be somewhat more open to thinking "hey, maybe it's something with genetics", but sadly, most kids and adults bring it upon themselves by sucking down 4+ cans of soda (a whole days worth of CALORIES at least, with no nutrients save artificial sugar...which isn't nutritional), 2 bowls of pure sugar for breakfast (otherwise known as cereal), a bag of candy as a snack, hotdogs&doretos for lunch, followed with a big mac for dinner. At least that's the case in America.