MPI EVA: Modern humans have evolved more effective protection against oxidative stress

Neanderthal variant of the protein glutathione reductase increases the risk of inflammatory bowel disease and vascular disease

Only a tiny fraction of all proteins in the human body show changes that make them unique compared to the corresponding proteins in Neanderthals and apes. researchers of Max Planck Institute for Evolutionary Anthropology in Leipzig and the Karolinska Institutet in Sweden have now investigated such a protein involved in protection against oxidative stress. They show that the variant of the protein found in modern humans provides better protection against inflammation and vascular disease than the Neanderthal variant.

What makes modern humans so unique is a question that has occupied research for a long time. One way to approach this question is to look at the proteins, or building blocks, in the body that exhibit changes that are common to almost all humans alive today and that occurred after we learned from the ancestors we know about the Neanderthals shared, had separated about 500.000 years ago. One of these changes affects the protein glutathione reductase, which is part of the body's defense against oxidative stress.

A new study led by Hugo Zeberg and Svante Pääbo examines the alteration of glutathione reductase in detail. The researchers from Karolinska Institutet and the Max Planck Institute for Evolutionary Anthropology show that the Neanderthal version of this protein generates more reactive oxygen radicals that cause oxidative stress. This is the third protein alteration in modern humans that has been studied so far.

legacy of the Neanderthals

The study also shows that some people alive today inherited the Neanderthal version of this protein when our ancestors interbred with them about 60.000 years ago. The researchers found that people who carry this Neanderthal version are now at higher risk of developing vascular disease and inflammatory bowel disease. Both are diseases associated with oxidative stress.

"The increases in risk that we are seeing are large - there is a multiple increase in risk of inflammatory bowel disease and vascular disease," says Zeberg. The researchers can only speculate as to why this particular change is one of the few unique changes found in almost all modern humans. “Stopping oxidative stress is a bit like stopping something from rusting. Perhaps the fact that we are living longer has caused this change,” says Pääbo.

Source: Press release of the MPI EVA from January 5th, 2022