This broken gene marathoners-and will humans conquer the world | Science

Despite our coach potato lifestyles, long-distance running is in our genes. A new study in the field of marathoners, giving the endurance to conquer territory, the predators, and eventually dominate the planet.

"This is very convincing evidence," says Daniel Lieberman, a human evolutionary biologist at Harvard University who was not involved with the work. "It's a nice piece of the puzzle about how humans come to be so successful."

Human ancestors first distinguished themselves by other primates by their unusual way of hunting prey. Instead of being a quick learner of energy-like cheetahs, they are simply outlasted and they have been kept running. It has had a significant impact on the climate changed 3 million years ago, and forested areas of Africa are becoming more widespread. Lieberman and others have identified skeletal changes that helped make such long-distance running possible, like longer legs. Others have also proposed that our ancestors' loss of fur and expansion of sweat tassels helped keep these runners cool.

Still, researchers say Herman Pontzer, an evolutionary anthropologist at Duke University in Durham, North Carolina, who was not involved with the work.

Some clues came 20 years ago, when Ajit Varki, a physician-scientist at the University of California, San Diego (UCSD), and colleagues unearthed one of the first genetic differences between humans and chimps: a gene called CMP-Neu5Ac Hydroxylase (CMAH). Other primates have this gene, which helps build a molecule called sialic acid that sits on cell surfaces. But humans have a broken version of CMAH, so they do not make this sugar, the team reported. Since then, Varki has implicated sialic acid in inflammation and resistance to malaria.

In the new study, Varki's team explored whether CMAH has any impact on muscles and running ability, in part because of having a muscular dystrophy-like syndrome when they do not have this gene. UCSD Graduate Student Jonathan Okerblom with a normal and broken version of CMAH (akin to the human version) on small treadmills. UCSD physiologist Ellen Breen closely examined their leg muscles before and after running different distances.

After training, the mice with the human version of the CMAH gene ran 12% faster and 20% longer than the other mice Proceedings of the Royal Society B. Lieberman says "Nike would pay a lot of money" for that kind of increase in performance.

The team discovered that the "humanized" mice had more tiny blood vessels branching into their leg muscles, and-even when isolated in a mice-controlled muscles. The humanlike mouse muscles used oxygen more efficiently as well. But the researchers still have no idea how to improve the endurance of the molecule.

Andrew Best, a biological anthropology graduate student at the University of Massachusetts (UMass) in Amherst, who was not involved with the work. Varki's team calculated that this genetic change happened 2 million to 3 million years ago, based on the genetic differences among primates and other animals.

That's "slightly longer than I would have expected for such a large shift in [endurance], "Says Best, as it predates some of the skeletal changes, which do not show up in the fossil record until much later. But to Pontzer, the date makes sense, as these ancestors needed endurance for walking and digging up food. "Maybe it's more than about running," he notes.

However, "Mice are not humans or primates," says Best adviser at UMass, Jason Kamilar, a biological anthropologist also not involved with the new work. "The genetic mechanisms in mice may not necessarily translate to humans or other primates."

Either way, says Pontzer, the study is going beyond the fossils and into what is actually going on in the bodies of ancient animals. "This is really energizing work; it tells us how much is out there to do. "