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Approximately two to three million years ago, researchers suggest that the genus Homo experienced a genetic mutation that caused the loss of a gene, called CMAH, that lead to humanity’s ability of being the best long-distance runners in the animal kingdom.

A team of researchers from the University of California, San Diego School of Medicine, came to this conclusion when they studied engineered mice that also lacked the gene.

They furthered their investigation into the effects of genetic differences on the origin of Homo when they witnessed the effects on fertility of the engineered mice with the mutation.

What fueled humanity’s ability to hunt in hot weather, pursue prey for much longer than other animals, and run long distances was the dramatic evolution of long legs, sweat glands that can dissipate a lot of heat, large feet and powerful gluteal muscles.

Researchers suggest that this dramatic evolution occurred during the CMAH mutation, where humans moved to arid savannahs in Africa instead of living in forests.

“Since mice were also more prone to muscle dystrophy, I had a hunch that there was a connection to the increased long distance running and endurance in Homo,” Ajit Varki, senior author and Distinguished Professor of Medicine and Cellular Molecular Medicine at UC San Diego School of Medicine, said. “But I had no expertise on the issue and could not convince anyone in my lab to organize this long-shot experiment.”

Jon Okerblom, a graduate student, decided to take part by using a mouse treadmill and mouse running wheels. With those, he examined the exercise capacity of the mice with the genetic mutation and found increased performance after 15 days of wheel running during the treadmill examination.

Ellen Breen, a research scientist in the division of physiology, confirmed observations of the mice including greater resistance to fatigue, more capillaries that increased oxygen supply and blood, and increased mitochondrial respiration and hand-limb muscle.

Loss of the CMAH in mice caused a genetic change that also enhanced skeletal muscle capacity for oxygen utilization. This observation in mice could suggest the mechanisms behind how early hominids, once tree dwellers, became hunter-gatherers in an open landscape. After the mutation occurred, there was a change that impacted almost every cell in the human body.

The researchers suggest that the use of sialic acids was altered after the mutation caused by an ancient pathogen that led to the loss of N-glycolylneuraminic acid, and the rise of another called N-acetylneuraminic acid.

In this study, the loss of the CMAH gene and the altering of sialic acids have been linked to long distance running and innate immunity in early hominids, meaning that this genetic mutation was more than a small change.

But the mutation of these two factors also have a downside including the association with increased risk of type 2 diabetes with certain sialic acids. Sialic acids are potentially a biomarker for cancer risk.

Varki concludes that the mutation is a double-edged sword stemming from “the consequence of a single lost gene and a small molecular change that appears to have profoundly altered human biology and abilities going back to our origins.”

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