A mutation of a single gene may have helped humans become optimal long-distance runners

Two or three million years ago, the functional loss of a single gene caused a series of significant changes in what would become the modern human species, ranging from fertility rates to risk increased cancer by eating red meat.

In a new article, published in the September 12 issue of Acts of the Royal Society BResearchers at the University of California San Diego School of Medicine report studies on mice that do not have the same gene, called CMAH, and the resulting data suggest that the lost gene may also have contributed to the well-documented claim of humanity to be among the best runners in the animal kingdom.

At about the same time as CMAH mutation took over, human ancestors passed from forest dwellers to life, mainly in the arid savannahs of Africa. While they were already walking upright, the bodies and abilities of these early hominids were changing dramatically, especially the major changes in biomechanics and skeletal physiology that resulted in long, elastic feet, big feet, powerful gluteal muscles dissipate heat much more effectively than other large mammals.

Such changes, say the scientists, have contributed to the emergence of human ability to travel long distances relentlessly, allowing ancestors to hunt in the heat while other carnivores rested and pursued their prey to their exhaustion. hunt.

"More than 20 years ago, we discovered this first obvious genetic difference between humans and our closest evolving relatives, chimpanzees," said lead author Ajit Varki, MD, Distinguished Professor of Medicine and Cellular Medicine and Molecular at the University of San Diego. Medicine and co-director of the UC San Diego / Salk Center for Academic Research and Training in Anthropology.

Given the approximate timing of the mutation and its documented impact on fertility in a mouse model with the same mutation, Varki and Pascal Gagneux, professor of anthropology and pathology, began to investigate how genetic difference could contribute to originally. of Homo, the kind that includes modern Homo sapiens and extinct species like Homo habilis and Homo erectus.

"Since mice were also more prone to muscular dystrophy, I thought there was a connection with the increase in running and the stamina of HomoSaid Varki, "but I did not have expertise on the subject and I could not convince anyone in my laboratory to organize this long experience."

In the end, a graduate student named Jon Okerblom took over, building mouse casters and borrowing a mouse pad. "We evaluated the exercise capacity (mice lacking CMAH gene), and noted an improvement in performance during treadmill tests and after 15 days of voluntary rolling, "said Okerblom, first author of the study. The researchers then consulted with Ellen Breen, Ph.D., a researcher in the Physiology Division. a part of the Department of Medicine of the Faculty of Medicine at the University of San Diego, who added that mice exhibited greater fatigue resistance, increased mitochondrial respiration and lower limb muscles.

Taken together, Varki said the data suggests CMAH the loss helped to improve the skeletal muscle 's ability to use oxygen. "And if the results translate into humans, they might have provided the first hominids with a selective advantage in their passage from trees to becoming permanent hunter-gatherers in the field."

When the CMAH mutated gene in the genus Homo Two or three million years ago, perhaps in response to evolutionary pressures caused by an ancient pathogen, hominids and modern humans have used sialic acids, a family of sugar molecules that cover surfaces. animal. points of contact for interaction with other cells and with the surrounding environment.

Human mutation results in the loss of a sialic acid called NOT– glycolylneuraminic acid (Neu5Gc), and accumulation of its precursor, called NOT-acetylneuraminic acid or Neu5Ac, which differs only by a single atom of oxygen.

This seemingly minor difference affects almost all types of cells in the human body and has proven to be a mixed blessing. Varki and others have linked the loss of CMAH Genes and sialic acids not only improved the ability to race long distance, but also improved innate immunity in early hominids. Sialic acids can also be a biomarker of cancer risk.

Conversely, they have also reported that some sialic acids are associated with an increased risk of type 2 diabetes; may contribute to a high risk of cancer associated with the consumption of red meat; and start the inflammation.

"They are a double-edged sword," said Varki. "The consequence of a single gene lost and a small molecular change that seems to have profoundly altered human biology and abilities going back to our origins."

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More information:
Inactivation of human-type Cmah in mice increases resistance to stroke and reduces muscle fatigue: implications for human evolution, Acts of the Royal Society B, rspb.royalsocietypublishing.or … .1098 / rspb.2018.1656