Friday, September 17, 2010

Don't count on evolution to eradicate diabetes

Gene variants associated with an increased risk for type-1 diabetes and rheumatoid arthritis may confer previously unknown benefits to their human carriers, say researchers at the Stanford. As a result, the human race may have been evolving in the recent past to be more susceptible, rather than less, to some complex diseases.

According to the lead researcher, "Everything we've been taught about evolution would indicate that we should be evolving away from developing type 1 diabetes. But instead, we've been evolving toward it. Why would we have a genetic variant that predisposes us to a deadly condition?" The researchers speculate that at least some of the risky changes may protect carriers against certain viruses and bacteria -- a trade-off that may have made evolutionary sense in the not-too-distant past when infectious diseases were devastating and largely untreatable.

According to the study, published in Science One, the idea that disease-causing genes can be beneficial is not new. The most clear-cut case involves a gene variant that, when present in two copies, causes sickle cell anemia, which can result in severe pain, organ damage and death. Although it seems that natural selection would work to eliminate the disorder, the variant remains prevalent in some areas of Africa because people with just a single copy are less susceptible to malaria. Evolutionarily the trade-off is worth it: Far more people are protected from malaria than ever develop sickle cell anemia even in today's environment. Unlike sickle cell anemia, which is caused by a mutation in just one gene, many complex diseases are associated with several variants -- specific locations in the DNA where the nucleotide "letters" vary between individuals. These locations are known as SNPs, for single nucleotide polymorphisms. Some of these SNPs are associated with an increased disease risk, while others protect against developing the disease.

When calculating an individual's overall genetic risk, it's necessary to consider the net effect of all of his or her variants. Researchers picked seven well-known conditions to study: type-1 and type-2 diabetes, rheumatoid arthritis, hypertension, Crohn's disease, coronary artery disease and bipolar disorder. Previous genome wide association studies have identified several hundred SNPs associated with each disorder. The Stanford researchers found that of the top SNPs associated with type-1 diabetes, 80 have been recently increasing in prevalence, meaning that they underwent positive selection. Of these, a surprising 58 are associated with an increased risk of the disorder, while 22 appear protective. Similarly, SNPs associated with an increased risk for rheumatoid arthritis were found to be positively selected. In contrast to type-1 diabetes and rheumatoid arthritis, we're evolving away from a tendency to develop Crohn's disease. Results for the other three disorders -- type-2 diabetes, coronary artery disease and bipolar disorder -- showed that protective and risky SNPs were positively selected in about equal proportions.

Regardless of the reason, some evolutionary tenets still apply. Healthier people are, presumably, more likely to reproduce and pass those same genes -- be they protective or risky -- to their offspring. When conditions changed because of differences in diet, exposures or location as populations move around the globe, carriers of the risky SNPs began to develop the conditions we struggle with today.

"Even though we've been finding more and more genetic contributions to disease risk," said researchers, "that's not really an appealing answer. There have got to be some other reasons why we have these conditions."

Bonnie - the reason is simple. Since agriculture was created, and humans began consuming grains approximately 10,000 years ago, we have been negatively expressing our genetic SNPs. Epigenetics, which deems how our genes are expressed, are driven by our lifestyle choices. Grain consumption is diametrically opposed to our genetic makeup. We are trying to genetically overcome millions of years of evolution based upon a paleolithic diet.

A new study in Journal Nature reveals that our use of stone tools to consume meat dates roughly one million years earlier than previously believed with Lucy's species, Australopithecus Afarensis. With this new discovery, we have a million more years of evolution to overcome in being able to tolerate grains.

These geneticists and paleontologists should get together with epigeneticists to produce a compelling argument for governments and the World Health Organization to curtail grain consumption worldwide. In its place, agriculture can grow more epigenetically harmonizing crops called vegetables and fruit!

If you must consume grains, one way to try to lower your risk from developing diabetes is to have a high level of magnesium, according to a study in the Journal of the American College of Nutrition.

For more on how epigenetics is key to evolution, here is a compelling article.

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