Molecular change helps balance nutrition and detoxification in modern humans

A control switch in an enzyme is present in most modern humans, but absent in Neandertals

To the point

• A modern human enzyme variant: Scientists have identified a molecular control switch in the enzyme NAT1 that is present in most people today but was absent in Neandertals.
• Inherited Neandertal version: Around two per cent of people alive today carry an older version of NAT1, which they inherited from Neandertals.
• Balancing folate and detoxification: NAT1 helps to process folate (an essential vitamin) and harmful environmental substances. The modern human version can be switched off by a chemical tag, helping conserve folate.
• Possible relevance for pregnancy and diet: Conserving folate is particularly important during pregnancy. Researchers suggest that the modern control mechanism may have helped humans adapt to diets containing less folate, though this hypothesis requires further testing.

Humans rely on enzymes to process substances from their surroundings, including nutrients and vitamins, but also harmful chemicals such as those found in cigarette smoke. One of these enzymes is called NAT1. It has two roles in our bodies. First, it is involved in breaking down the vitamin folate, which is found in leafy greens and fruits. Folate is especially important during pregnancy because low folate levels increase the risk of birth defects. Second, the enzyme helps detoxify harmful substances from the environment that may cause cancer.

In a new study, scientists at the Max Planck Institute for Evolutionary Anthropology in Leipzig found that two percent of people today carry a Neandertal version of this enzyme. “We found that some modern humans inherited an old version of NAT1 from Neandertals when the two groups interbred around 50,000 years ago,” says Mikel Lana Alberro, lead bioinformatician of the study.

A molecular control switch in modern humans

The scientists found that the newer version of the enzyme, which almost everyone today carries, differs from the older version carried by Neandertals by two changes. One of these changes creates a control point where a chemical “tag” can be added. This tag turns down the enzyme’s activity. “We tested the two versions of the enzyme and found that they behave the same when the control point is not used,” explains Luise Fast, lead author of the study. “But when we added the chemical tag to the modern human version, its activity dropped considerably. The older version cannot be controlled in this way.”

This may allow modern humans to turn down the enzyme’s activity when it is useful to conserve folate. This is the case during pregnancy, when conserving folate can help decrease the risk of birth defects. This may have been important, for example, when humans started to rely more on cooking food, which can destroy folate. Today, pregnant women are often advised to take extra folate. “In modern humans, this control mechanism may therefore allow for a diet with less folate,” says Hugo Zeberg, senior author of the study. “But the study presents this as a hypothesis that still needs to be tested in developmental models,” he points out.