Home / Science / A single gene mutation may have helped people become optimal long-distance runners

A single gene mutation may have helped people become optimal long-distance runners

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Two to three million years ago, the functional loss of a single gene triggered a series of significant changes in what would eventually be the modern human species, which changed everything from fertility rates to increased risk of cancer from eating red meat.

In a new paper, published in the September 1

2 issue of Proceedings of the Royal Society B researchers at the University of California report San Diego School of Medicine on studies of mice designed to lack the same gene, called CMAH and resulting data suggesting the lost gene may also have contributed to the well-documented claim of mankind to be among the best long-distance runners in the animal kingdom.

At about the same time When the mutation took CMAH human ancestors passed from forestry to life especially in Africa's dry savannas. While they were already upright, the body and abilities of these early hominids developed dramatically, in particular, major changes in skeletal biomechanics and physiology that resulted in long resilient bones, big feet, powerful gluteal muscles and an expansive system of sweat glands to disperse the heat much more efficiently than other major mammals.

Such changes, say researchers, contributed to burning the rise of the human ability to drive long stretches relatively tirelessly, so that the ancestors chased today's heat when other carnivores rested and pursued their fatigue point, a technique called persistence hunt.

"We discovered this first clear genetic difference between humans and our closest living evolutionary relatives, the chimpanzees, more than 20 years ago," says senior writer Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine and co-chair of the UC San Diego / Salk Center for Academic Research and Education in Anthropology.

Given the approximate time of the mutation and its documented impact on fertility in a mouse model with the same mutation, Varki and Pascal Gagneux, Ph.D., Professor of Anthropology and Pathology, began to investigate how the genetic difference may have contributed to the origin of Homo genus that includes modern Homosexuality and extinct species such as Homo habilis and Homo erectus .

"Because the mice were also more prone to muscle dystrophy, I had the impression that there was a link to the increased long-distance running and endurance of Homo ", Varki said, "but I had no expert knowledge on the subject and could do not convince anyone in my lab to organize this long-term experiment. "

In the end, a doctoral student named Jon Okerblom took the task of building muscular wheels and borrowing ingrained mouse milk bands. "We evaluated the exercise capacity (in mice missing the CMAH genes), and noted increased performance during third-party testing and after 15 days of voluntary wheelbinding," said Okerblom, the first author of the study. The researchers then consulted Ellen Breen, Ph.D. , a physiological researcher, part of the Department of Medicine at the UC San Diego School of Medicine, which made observations that the mouse showed greater resistance to fatigue, increased mitochondrial respiration and backward muscles, with more capillaries increasing blood and oxygen supply.

Overall, Varki said data suggests CMAH loss contributed to improved skeletal muscle capacity for oxygen utilization. "And if the find translates to humans, they may have given early hominids with a selective advantage in their move from tree to become permanent hunter collectors in the open area. "

When CMAH The gene mutated in the genus Homo two to three million years ago, perhaps in response to evolutionary pressures caused by an old pathogen, it changed how the following hominids and modern humans used sialic acids – a family of sugar molecules that coat the surfaces of all animal cells, where they serve as important focal points for interaction with other cells and with the environment.

The human mutation causes the loss of a sialic acid called N glycollylneuraminic acid (Neu5Gc), and the accumulation of its predecessor, called N -acetylneuraminic acid or Neu5Ac, which differs only a single oxygen room.

This apparently minor difference affects almost all cell types in the human body y-and has proved to be a mixed blessing. Varki and others have linked the loss of the CMAH gene and sialic acids in order not only to improve long-distance driving ability, but also to improve congenital immunity in early hominids. Sialic acids can also be a cancer biomarker.

Conversely, they have also reported that some sialic acids are associated with increased risk of type 2 diabetes. can contribute to increased cancer risk associated with red meat consumption and trigger inflammation.

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

Explore further:
Missing molecule increases the risk of diabetes in humans

More information:
Human Cmah Inactivation in Mice Increases Continuous Perseverance and Reduces Muscle Fatigue: Consequences for Human Development, Progress of Royal Society B rspb.royalsocietypublishing.or … .1098 / rspb.2018.1656

Journal Reference:
Progress of Royal Society B

Provided by:
University of California – San Diego

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