Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A single DNA tweak leads to blond hair

02.06.2014

A single-letter change in the genetic code is enough to generate blond hair in humans, in dramatic contrast to our dark-haired ancestors. A new analysis by Howard Hughes Medical Institute (HHMI) scientists has pinpointed that change, which is common in the genomes of Northern Europeans, and shown how it fine-tunes the regulation of an essential gene.

"This particular genetic variation in humans is associated with blond hair, but it isn't associated with eye color or other pigmentation traits," says David Kingsley, an HHMI investigator at Stanford University who led the study. "The specificity of the switch shows exactly how independent color changes can be encoded to produce specific traits in humans." Kingsley and his colleagues published their findings in the June 1, 2014, issue of the journal Nature Genetics.

Kingsley says a handful of genes likely determine hair color in humans, however, the precise molecular basis of the trait remains poorly understood. But Kingsley's discovery of the genetic hair-color switch didn't begin with a deep curiosity about golden locks. It began with fish.

For more than a decade, Kingsley has studied the three-spined stickleback, a small fish whose marine ancestors began to colonize lakes and streams at the end of the last Ice Age. By studying how sticklebacks have adapted to habitats around the world, Kingsley is uncovering evidence of the molecular changes that drive evolution.

In 2007, when his team investigated how different populations of the fish had acquired their skin colors, they discovered that changes in the same gene had driven changes in pigmentation in fish found in various lakes and streams throughout the world. They wondered if the same held true not just in the numerous bodies of water in which sticklebacks have evolved, but among other species.

Genomic surveys by other groups had revealed that the gene – Kit ligand – is indeed evolutionarily significant among humans. "The very same gene that we found controlling skin color in fish showed one of the strongest signatures of selection in different human populations around the world," Kingsley says. His team went on to show that in humans, different versions of Kit ligand were associated with differences in skin color.

Furthermore, in both fish and humans, the genetic changes associated with pigmentation differences were distant from the DNA that encodes the Kit ligand protein, in regions of the genome where regulatory elements lie.

"It looked like regulatory mutations in both fish and humans were changing pigment," Kingsley says. Kingsley's subsequent stickleback studies have shown that when new traits evolve in different fish populations, changes in regulatory DNA are responsible about 85 percent of the time. Genome-wide association studies have linked many human traits to changes in regulatory DNA, as well. Tracking down specific regulatory elements in the vast expanse of the genome can be challenging, however.

"We have to be kind of choosy about which regulatory elements we decide to zoom in on," Kingsley says. "We thought human hair color was at least as interesting as stickleback skin color." So his team focused its efforts on a human pigmentation trait that has long attracted attention in history, art, and popular culture.

Kit ligand encodes a protein that aids the development of pigment-producing cells, so it made sense that changing its activity could affect hair or skin color. But the Kit ligand protein also plays a host of other roles throughout the body, influencing the behavior of blood stem cells, sperm or egg precursors, and neurons in the intestine. Kingsley wanted to know how alterations to the DNA surrounding this essential gene could drive changes in coloration without comprising Kit ligand's other functions.

Catherine Guenther, an HHMI research specialist in Kingsley's lab, began experiments to search for regulatory switches that might specifically control hair color. She snipped out segments of human DNA from the region implicated in previous blond genetic association studies, and linked each piece to a reporter gene that produces a telltale blue color when it is switched on. When she introduced these into mice, she found that one piece of DNA switched on gene activity only in developing hair follicles. "When we found the hair follicle switch, we could then ask what's different between blonds and brunettes in northern Europe," Kingsley said. Examining the DNA in that regulatory segment, they found a single letter of genetic code that differed between individuals with different hair colors.

Their next step was to test each version's effect on the activity of the Kit ligand gene. Their preliminary experiments, conducted in cultured cells, indicated that placing the gene under the control of the "blond" switch reduced its activity by about 20 percent, as compared to the "brunette" version of the switch. The change seemed slight, but Kingsley and Guenther suspected they had identified the critical point in the DNA sequence.

The scientists next engineered mice with a Kit ligand gene placed under the control of the brunette or the blond hair enhancer. Using technology developed by Liqun Luo, who is also an HHMI investigator at Stanford, they were able to ensure that each gene was inserted in precisely the same way, so that a pair of mice differed only by the single letter in the hair follicle switch—one carrying the ancestral version, the other carrying the blond version.

"Sure enough, when you look at them, that one base pair is enough to lighten the hair color of the animals, even though it is only a 20 percent difference in gene expression," Kingsley says. "This is a good example of how fine-tuned regulatory differences may be to produce different traits. The genetic mechanism that controls blond hair doesn't alter the biology of any other part of the body. It's a good example of a trait that's skin deep—and only skin deep."

Given Kit ligand's range of activities throughout the body, Kingsley says many such regulatory elements are likely scattered throughout the DNA that surrounds the gene. "We think the genome is littered with switches," he says. And like the hair color switch, many of the regulatory elements that control Kit ligand and other 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. The trick is, which switches have changed to produce which traits?

"Despite the challenges, we now clearly have the methods to link traits to particular DNA alterations. I think you will see a lot more of this type of study in the future, leading to a much better understanding of both the molecular basis of human diversity and of the susceptibility or resistance to many common diseases," Kingsley said.

Jim Keeley | Eurek Alert!
Further information:
http://www.hhmi.org

Further reports about: DNA HHMI activity differences experiments genes protein regulatory skin study

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>