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Atul Butte is a lead researcher at the Stanford University School of Medicine. His team is developing new methods for testing which environmental factors correlate with type 2 diabetes. (Gary Reyes/Mercury News File)

The same genes that cause disease in modern humans may have protected against more deadly ailments in our primitive past, according to a new study by Stanford researchers.

Scientists have long wondered why the prevalence of diseases such as Type 1 diabetes and rheumatoid arthritis seem to be increasingly common -- because evolution's "survival-of-the-fittest" theory should dictate that we'd lose such disabling traits.

But an analysis by Dr. Atul Butte and graduate student Erik Corona of Stanford University's School of Medicine suggests that the gene variants that now cause these ailments were once useful, helping shield our forebears from a bigger killer: infectious disease.

"When a child is diagnosed, parents ask: Why is this in our genes?" said Butte, assistant professor of pediatric cancer biology and a bioinformatics expert at Stanford's Lucile Packard Children's Hospital.

"Now we have an answer," he said. "It is in our genes because at one point in human history, these genetic variants were protective against viruses and bacteria."

Studying gene sequences derived from a huge 17,000-person database in England, they focused on the variants linked to seven well-known conditions: Type 1 and Type 2 diabetes, rheumatoid arthritis, hypertension, Crohn's disease, coronary artery disease and bipolar disorder.

Based on the characteristics of the variants, and their location on the genome, they could tell whether the disease-causing traits are increasing or decreasing over time.

"We asked the question: When we look at human evolution, which is still under way, are we evolving towards, or away, from disease?" Butte said. "It's a simple question that no one had answered in this way."

In their paper, published in the current issue of the Public Library of Science ONE, they say there's an established link between Type 1 diabetes and the body's ability to protect against enterovirus infection, which can cause high fever, diarrhea and sometimes death.

Similarly, they say, there is a strong correlation between rheumatoid arthritis and tuberculosis. Populations with a high incidence of one have a lower incidence of the other.

They found that variants associated with Type 1 diabetes have been increasing in prevalence, meaning that they were evolutionarily useful. A similar trend was seen in rheumatoid arthritis.

In contrast, humans are evolving away from a tendency to develop Crohn's disease. No patterns were seen in the other conditions.

Perhaps people in some parts of the world, or in earlier times, weren't exposed to the things that trigger modern-day diabetes or arthritis, the scientists speculate. These people would enjoy only the protective effects -- and pass on the trait to future generations.

When conditions changed, due to differences in diet or environment, carriers of these genes began to develop the conditions we struggle with today.


The most well-known example involves a gene variant that, when present in two copies, causes deadly sickle cell anemia. But people with just a single copy are less susceptible to malaria. Evolutionarily, the trade-off is worth it.

The Stanford team is now expanding its investigation to include even more genes and diseases.

Contact Lisa M. Krieger at 408-920-5565.