Harvard team uses mice to elucidate key changes in human evolution

David L. Ryan/Globe staff/2008 file photo
David L. Ryan/Globe staff/2008 file photo
Pardis Sabeti, a systems biologist at Harvard University and the Broad Institute is one of the leaders of new research into human evolution at the genetic level

Harvard researchers are using scientific tools more often deployed to probe major health problems to understand the recent evolution of humans. In a study published Thursday, scientists used DNA blueprints from living people and experiments in laboratory mice to gain insight into a genetic change that became common among East Asians some 30,000 years ago.

They showed that the particular gene variant causes the development of more sweat glands, and speculate it could have given people a survival advantage in the humid climate of the region.

A statistical tool the scientists developed a few years ago highlighted the particular version of the gene, called EDAR, telling them it had been favored by human evolution. They knew the gene was associated with certain traits—differences in tooth shape and thicker hair. But big questions remained: Did the gene cause the tooth and hair differences? What advantage could it have given people?

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Thus far, most of the work in this field had more to do with finding the genetic underpinnings of traits scientists already understood, such as the spread of the gene that allows human beings to continue to digest milk in adulthood. This time, they wanted to use the genes as a clue to understand what traits were adaptive during human evolution.

To help unravel the story, a large interdisciplinary team used genetic manipulation to create a laboratory mice that had the same version of the human gene. In the study appearing in the journal Cell, they reported that the particular mutation that is prevalent among East Asians not only caused the mice to have thicker hair, but more sweat glands on their footpads and changes in the structure of their mammary glands.

The sweat gland finding was especially interesting. Sweat, it turns out, is one of the things that sets people apart from other animals. Even closely-related chimpanzees can sweat through only a limited number of body areas, such as their hands or nose. Our ability to sweat is one of the traits that has made human beings so good at running long distances—which may have been helpful for hunter-gatherers.

“It gives you a history of what traits were critical for survival in humans,” said Pardis Sabeti, associate professor of systems biology at Harvard University and a member of the Broad Institute, a Cambridge genomics research center.

To make sure they weren’t just getting an odd result in a mouse, the team was also simultaneously studying people. Using publicly available data and a computational analysis, the scientists estimated that the particular version of the gene evolved and spread in central China between 13,000 and 40,000 years ago.

The researchers studied a group of Han Chinese who carried the same version of the gene as the mice and measured their traits: the people, like the mice, had more sweat glands.

Sabeti said it was surprising that so many different traits were linked to the same gene. It raises the possibility that some of those biological traits could have become more common because they happened to be linked to the same gene as one advantageous trait.

Around the time the particular version of the gene emerged, China was humid and warm. It then became cooler but remained humid, suggesting that sweating efficiently could be advantageous. But the alterations to the mammary gland could also be evolutionarily significant. Changes in the mammary glands could potentially affect breast milk production, an important biological function that could influence the survival of offspring and have evolutionary consequences.

The researchers are already developing a lab mouse that carries a different mutation in a gene that is often found along with the one in EDAR. Depending on what they find, that gene’s biological functions may help elucidate which traits were the ones that became more common because of evolution, and which were merely along for the ride.

And in a separate study published in Cell on Thursday, Sabeti and colleagues reported they had applied their statistical method to a large set of whole genomes and found 412 new candidates for genes that underwent evolution.

They’ve already begun to examine one of those mutations in detail, and found that a gene involved in the immune system developed a mutation that spread through populations that appears to make it more difficult for bacteria to cause an infection.

Ultimately, Sabeti hopes that her study of advantageous genetic traits in human evolution will lead her to new understandings of disease, since many adaptations may have helped people resist or survive infections.