Kingsley, a brunet, said the study, published today in Nature Genetics, also offers a powerful insight into the workings of the human genome. The mutation doesn't alter the protein production of any of the 20,000 genes in the human genome, he said. Instead, in people of European ancestry, it causes blond hair through a 20 percent "turn of the thermostat dial" that regulates a signaling gene in the hair follicles of the skin.
Elsewhere in the body, that signaling gene is involved in the formation of blood, egg, sperm, and stem cells. Turning such a gene entirely on or off could be devastating. But a tiny mutation that tweaks the gene's activity in only one area—in this case the skin—allows for harmless changes, he said.
Pardis Sabeti, a computational biologist at Harvard University and Broad Institute who was not involved in the research, said the study is a "beautiful demonstration" of this kind of tweaking, which has previously been poorly understood. To find a single letter change and prove that it is a big driver of blond hair is a major scientific accomplishment, she said.
To find the blond-hair gene mutation, Kingsley and his team looked at an area of the genome previously linked to blondness in people fromIceland and the Netherlands. They painstakingly identified the exact letter change that gives a person blond hair.
The researchers tested what that letter change did in human skin cells grown in a petri dish. The cells showed a reduction in activity in the switch that controls the signaling gene. Then Kingley's group bred lines of mice that either had the mutation or didn't have it. The single-letter change didn't create blond mice, but those with the mutation had coats of a lighter color than those without.
Learning the mechanism behind something as common—and as universally recognizable—as hair color, can help explain how genes work in other contexts, such as illnesses, where the stakes are higher, Kingsley said. "Understanding these principles will help people ... trying to find drugs for diseases."
Hopi Hoekstra, a professor of genetics at Harvard who was not involved in the research, said the new finding confirms what researchers had long suspected: that small changes in gene expression caused by only a single DNA base pair change can lead to major changes in traits.
Hair color "is a great starting point to do this type of molecular dissection" because it's simple to see whether the mutation results in a change in appearance, she said. "But it highlights how difficult this is going to be for more complex human traits, like mental illness, which we've never been very good at measuring."
The blond hair mutation—or variant—is not genetically linked to any other traits, even eye color, Kingsley said, showing that none of our stereotypes about blonds are true. In contrast, many other human variants, such as some that cause red hair, are known to affect the protein structure of genes, and therefore trigger changes everywhere in the body the gene is expressed. Red hair, fair skin, and lighter eyes tend to travel as a package, he said, and may even be genetically paired with greater sensitivity to pain and temperature changes—though probably not fiery tempers.
Source: nationalgeographic.com by Karen Weintraub