Our bodies quit making vitamin C to battle parasites

According to textbooks, humans lost the ability to make vitamin C because our diet provided enough of it. However, research in animals suggests this loss might have helped our ancestors fight certain parasites.

Most animals produce vitamin C using an enzyme called GULO. About 60 to 70 million years ago, a mutation in our primate ancestors disabled the GULO gene. The same mutation has occurred in other animals, such as many bats and some rodents, including guinea pigs.

No harm, no evolutionary foul

The common explanation in biology is that if animals get enough vitamin C from their regular diet, losing the ability to make it internally causes no harm.

In such cases, a mutation in the GULO enzyme, which is responsible for producing vitamin C, would not reduce the animal’s chances of survival or reproduction.

Because the mutation does not create a disadvantage, natural selection would not act to protect or restore the functioning gene.

Over time, this change is seen as a neutral event in evolutionary terms – neither helping nor hurting the species in a significant way.

Vitamin C’s stem cell link

In 2017, Michalis Agathocleous at the University of Texas Southwestern Medical Center started to question whether this explanation told the whole story.

His research team discovered that vitamin C plays a crucial role in the health and function of blood-forming stem cells, which are essential for producing new blood cells.

The finding raised an important question: if the ability to produce vitamin C internally is truly unnecessary for animals that consume plenty of it, why do so many species with naturally vitamin-C-rich diets still keep a fully working GULO enzyme?

This puzzle suggested there might be other evolutionary pressures or benefits influencing the retention of the gene.

A hidden evolutionary edge

One difference is that animals with the enzyme keep vitamin C levels constant in their blood. Humans, however, see fluctuations, with levels dropping significantly during food shortages.

If making vitamin C offers benefits, why lose the ability? One evolutionary explanation is disease protection. Some traits disappear because losing them helps survival.

Agathocleous’s colleagues later found that schistosome flatworms, which cause schistosomiasis, lay more eggs when given extra vitamin C.

Testing the parasite protection theory

These parasites enter through the skin and mature inside animals. The symptoms often come from immune reactions to their eggs.

To test the idea, researchers deleted the GULO gene in mice. When fed a low-vitamin C diet, these mice resisted infection symptoms and did not pass eggs after exposure to schistosomes. Mice with the enzyme shed many eggs and mostly died.

“What we have done is provide evidence that there is a benefit,” said Agathocleous. While proof of positive selection in our ancestors is impossible, the results make it plausible.

Theory tied to gene loss

Recent theoretical work suggests that losing certain biosynthetic abilities, like vitamin C production, may result from evolutionary trade-offs.

If an environmental source of the nutrient is reliable, natural selection might favor losing the costly metabolic pathway. In some cases, the loss could alter immune responses in ways that protect against specific pathogens.

Such changes can also influence the gut microbiome. Variations in nutrient availability can reshape microbial communities, affecting both immunity and metabolism.

This interaction among diet, metabolism, and immunity may have played a role in shaping our evolutionary path.

Vitamin C loss aids survival

The theory also proposes that losing a metabolic function can reduce oxidative stress from overproduction of certain compounds. For vitamin C, this could mean avoiding excessive antioxidant levels that might disrupt normal immune signaling.

Over time, these subtle benefits could outweigh the disadvantages of dependency on dietary sources, especially in environments where vitamin-rich foods were abundant.

In the case of our primate ancestors, the trade-off may have been a small price to pay for greater resilience against harmful parasites.

“While many textbooks do state this might be a ‘use or lose it’ situation for the gene GULO, many scientists, including me, believe that there is sufficient evidence to support an evolutionary advantage to this gene loss,” said Deborah Good at Virginia Tech. “Parasite protection could be one of these.”

The study is published in bioRxiv.

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