A Benefit to Diabetes-Causing Genes?

Researchers at Stanford University have come to a surprising conclusion: That humans may have evolved to become more, rather than less, susceptible to a variety of complex conditions such as Type 1 diabetes and rheumatoid arthritis. It appears that genetic variants that predispose people to these conditions may have protected our ancestors from potentially deadly illnesses in the past.

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To determine why certain diseases are becoming increasingly common, the researchers analyzed gene sequences from a 17,000-person database in England, focusing specifically on gene variants associated with Type 1 diabetes, Type 2 diabetes, rheumatoid arthritis, hypertension (high blood pressure), Crohn disease, coronary artery disease, and bipolar disorder. They discovered that the gene variants associated with Type 1 diabetes and rheumatoid arthritis have been increasing in prevalence, and according to the researchers, this indicates an evolutionary benefit to these variants. (No such link was found for Type 2 diabetes.)

What could those benefits possibly be? The scientists note that there is an established genetic link between increased risk of developing Type 1 diabetes and protection against enterovirus infection, a type of illness that can lead to diarrhea, high fever, and death. Another well-established example of disease-causing genes having benefits is the relationship between sickle cell anemia and malaria: Having two copies of the sickle cell gene results in the development of sickle cell anemia, but having a single copy of the variant decreases a person’s susceptibility to malaria.

The study authors speculate that in earlier times or in certain areas of the world, people may not have been exposed to triggers for diseases such as Type 1 diabetes and rheumatoid arthritis, so that only the protective benefits of the gene variants were expressed — thereby increasing the likelihood that these variants would be passed on to future generations. When humans began to migrate around the globe and were exposed to new diets, environments, and other potential triggers, those people with the risky gene variants started developing the conditions based on their genetic predisposition.

According to senior author Atul Butte, MD, PhD, “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? Now we have an answer. It is in our genes because at one point in human history, these genetic variants were protective against viruses and bacteria.”

Several members of the investigative team are expanding their research to look at other gene variants and diseases to see if evolutionary benefit may have played a role in the development of these conditions as well.

For more information about the research, read the articles “Evolution May Have Pushed Humans Toward Greater Risk for Type 1 Diabetes” or “Evolution: Stanford study suggests disease-causing genes were once beneficial” or see the study in The Public Library of Science One.

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