Blondes have more fun, the saying goes, and so an entire industry of commercial hair dye has been promoted for decades. But in the sci-fi future — when cars are driverless and our individual traits are selected prenatally in a lab — parents may simply flip on a genetic switch in order to produce a fair-haired child. Or so you might imagine after reading the latest research from scientists at Howard Hughes Medical Institute (HHMI), Stanford University. They found a single letter change in your DNA is enough to fine-tune the regulation of an essential gene and results in blonde hair.

“The genetic mechanism that controls blond hair doesn't alter the biology of any other part of the body,” said Dr. David Kingsley, an investigator at HHMI, who led the study published in Nature Genetics. “It's a good example of a trait that's skin deep — and only skin deep."

Eye-Catching Hair

Among the first traits we notice in a stranger is hair color. Compared to other hues, blonde is a virtual light bulb bright enough to cause us to swivel our necks each time a fair-haired person appears. This fact has been exploited by entertainers time and again; Marilyn Monroe’s hair was naturally more honey than platinum, while Justin Timberlake, Beyonce, and Madonna have all preferred the bottle blonde look to their natural dark locks at different times in their career.

Surprisingly, Kingsley’s thoughts have been occupied, until recently, by something other than blonde hair; he has been researching the three-spined stickleback for more than a decade. Yet, in 2007, when his team of researchers discovered changes in the same gene had driven changes in pigmentation of this fish, he couldn’t help but wonder: Does the same hold true for other species?

Scientists have long believed it’s just a handful of genes that decide hair color, but they’ve never understood the precise molecular basis behind the trait. To learn more, Kingsley’s team of researchers snipped out segments of human DNA from a region identified in previous studies of genetic blondeness. Next, they linked these to a reporter gene that produces a blue color when it is switched on; here they discovered a single letter of genetic code differed from person to person with different hair colors. "When we found the hair follicle switch, we could then ask what's different between blonds and brunettes in northern Europe," Kingsley said.

After more testing and experiments, the team identified the critical point in the DNA sequence and then engineered mice with each gene inserted in precisely the same way. Next, the researchers produced a pair of mice differing by only a single letter in the hair follicle switch, with one carrying the usual version, the other carrying the blond version. What did they find?

With only a 20 percent difference in gene expression, one mouse was blonde, the other not.

This shows how fine-tuned regulatory differences may produce different traits. "We think the genome is littered with switches," Kingsley said in a press release. Just like the hair color switch, many regulatory elements that control genes may subtly adjust activity. "A little up or a little down next to key genes — rather than on or off — is enough to produce significant differences,” he explained.

Looking ahead, Kingsley predicts more studies will focus on variations to understand the molecular basis for human diversity as well as susceptibility (or resistance) to common diseases. “Despite the challenges, we now clearly have the methods to link traits to particular DNA alterations,” Kingsley concluded.

 

Source: Guenther CA, Tasic B, Luo L, Bedell MA, Kingsley DM. A molecular basis for classic blond hair color in Europeans. Nature Genetics. 2014.