The functional loss of a single gene may have helped humans become one of the best long-distance runners in the animal kingdom, a study has found.
Researchers at the University of California San Diego in the US studied mice engineered to lack the gene called CMAH.
Two to three million years ago, the functional loss of CMAH triggered significant changes in what would eventually become the modern human species, altering everything from fertility rates to increasing cancer risk from eating red meat, researchers said.
The study, published in the journal Proceedings of the Royal Society B, suggests that the lost gene may have contributed to humanity's well-documented claim to be among the best long-distance runners in the animal kingdom.
At roughly the same time as the CMAH mutation took hold, human ancestors were transitioning from forest dwellers to life primarily upon the arid savannahs of Africa.
While they were already walking upright, the bodies and abilities of these early hominids were evolving dramatically, researchers said.
Major changes in skeletal biomechanics and physiology resulted in long, springy legs, big feet, powerful gluteal muscles and an expansive system of sweat glands able to dissipate heat much more effectively than other larger mammals, they said.
Such changes, scientists say, helped fuel the emergence of the human ability to run long distances relatively tirelessly.
This allowed our ancestors to hunt in the heat of the day when other carnivores were resting and to pursue prey to their point of exhaustion, a technique called persistence hunting, they said.
"We discovered this first clear genetic difference between humans and our closest living evolutionary relatives, the chimpanzees, more than 20 years ago," said Ajit Varki, a professor at UC San Diego School of Medicine.
Researchers investigated how the genetic difference might have contributed to the origin of Homo, the genus that includes modern Homo sapiens and extinct species like Homo habilis and Homo erectus.
"We evaluated the exercise capacity (of mice lacking the CMAH gene), and noted an increased performance during treadmill testing and after 15 days of voluntary wheel running," said graduate student Jon Okerblom.
Ellen Breen, a research scientist at the UC San Diego, observed that the mice displayed greater resistance to fatigue, increased mitochondrial respiration and hind-limb muscle, with more capillaries to increase blood and oxygen supply.
Varki said the data suggest CMAH loss contributed to improved skeletal muscle capacity for oxygen utilisation.
"And if the findings translate to humans, they may have provided early hominids with a selective advantage in their move from trees to becoming permanent hunter-gatherers on the open range," he said.
When the CMAH gene mutated in the genus Homo two to three million years ago, perhaps in response to evolutionary pressures caused by an ancient pathogen, it altered how subsequent hominids and modern humans used sialic acids.
It is a family of sugar molecules that coat the surfaces of all animal cells, where they serve as vital contact points for interaction with other cells and with the surrounding environment.
Varki and other resaerchers have linked the loss of the CMAH gene and sialic acids to not just improved long-distance running ability, but also enhanced innate immunity in early hominids.
