Tiny mutation may have shaped modern humans, scientists say

About 30,000 years ago, a tiny mutation arose in a gene known as EDAR and began to spread rapidly in central China, eventually becoming common in the region.

This week, scientists at Harvard University offered some explanations for why the EDAR mutation may have been so successful — by observing how it affects mice, animals long used in disease research but never before pressed into service for the study of human evolution.


The small change, substituting one chemical letter of DNA for another, may have helped humans in Asia survive crippling heat and humidity by endowing them with extra sweat glands, the scientists reported Thursday in the journal Cell. It may also have made people with the mutation more attractive to the opposite sex by allowing them to grow thicker hair or fuller breasts.

The research showed how scientists are getting better at zeroing in on the key DNA changes that shaped who we are today. The analysis also revealed that mutations in genes involved in bone density, skin color and immune system function were likely pivotal in helping humans adapt to new environments as they spread throughout the world.

“You can let the genome tell you what’s been important in human evolution,” said Harvard computational geneticist Pardis Sabeti, senior author of the two studies published in Cell.

Living beings evolve through a process known as selection. Organisms with advantageous traits thrive, passing their DNA to another generation. Harmful traits die off when their hosts can’t live long enough to reproduce.

Scientists can recognize patterns in DNA that indicate a particular version of a gene has spread through a population because it boosts survival. But those beneficial mutations are usually passed down along with thousands of other variants that happen to live in their chromosomal neighborhood.

That has made it hard for researchers to determine exactly which genetic tweaks conferred the competitive advantage.

“It’s like you walk around a ghost town and you see the clues that something happened, but you don’t know exactly what or how,” said UC Santa Cruz biomolecular engineer Ed Green, who was not involved in the new studies.

Sabeti and an international group of colleagues are using multiple techniques to dig out the key drivers of human evolution in the avalanche of genetic data made possible by faster, cheaper sequencing technology. A single human genome contains 3 billion pairs of the chemical letters A, C, G and T.

To sort through all that, the researchers used powerful computers to identify genetic changes that seemed to be linked to evolutionary change. They examined the DNA of 179 people from Utah, East Asia and West Africa and revealed hundreds of potentially key variants, including mutations that made bones stronger and helped people absorb more vitamin D from the sun as they moved to northern latitudes.

Sabeti wanted to understand more about how these mutations influenced human traits. Such work requires experimentation — and that is where the mice entered the picture.

The EDAR gene was already known to influence hair thickness and to alter tooth shape in humans. But Sabeti wasn’t sure whether the mutation her team turned up was a key change that drove human evolution.

To arrive at an answer, she and her collaborators genetically engineered mice that had the Asian version of EDAR.

They found that, as with humans, the mice had thicker hair than their counterparts without the variant. They also displayed traits the researchers hadn’t expected to see, including more sweat glands and changes in their mammary glands. (The variant had no discernible effect on the animals’ teeth.)

Next, the team examined the fingertips and EDAR genes of 623 people in Taizhou, China, to see if those who had the mutation also had a larger number of active sweat glands. They did.

The results present a fuller picture of how the EDAR mutation may have helped drive evolution.

People who inherited the variant may have reproduced more successfully because having more sweat glands helped their bodies cool off in hot, humid weather.

Or it might have spread through sexual selection. Thicker hair may have been more appealing in a mate. In addition, the mutation could have changed breast size or shape, making people who had it more attractive to the opposite sex.

That scientists could study a mouse and reveal such insights into human evolution was “amazing,” said Green, who co-wrote an essay about the work that was also published in Cell on Thursday.

The story was similar for the TLR-5 gene, which is involved in protecting the body from certain bacteria. Instead of testing in mice, the scientists used cell cultures in lab dishes to demonstrate that the mutation reduced the immune system’s inflammatory response to a key protein in the bacterial pathogens.

The team’s analysis suggested that many of the key genetic changes weren’t in genes themselves, but in regions of the chromosome that scientists think contain instructions for how those genes should be turned on and off, or tuned up or down, Sabeti said.

The work offers a long-awaited view into the key mutations that billions of us share and that made us who we are, said David Kingsley, an evolutionary geneticist at Stanford University who was not involved in the new studies.

“We’re reading a book of information about our past that has never been available before,” he said.