Change hair color at the genetic level. How to make hair thicker and denser? Bioengineered epidermis for cosmetologists and pharmacologists

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Researchers at the Howard Hughes Medical Institute in Chevy Chase have found that changing just one letter in the DNA code can change a person's hair color.

David Kingsley, a research fellow at the institute, has long studied the evolution of sticklebacks, small fish that moved from the seas into lakes and streams at the end of the last ice age.

By exploiting the stickleback's ability to adapt to different environmental conditions, Kingsley and his colleagues were able to identify the molecular changes underlying its evolution.

Recently, they have turned their attention to the fact that the evolutionary changes in this fish can lead to interesting conclusions about the evolution of humans and other species.

In their latest research, Dr Kingsley's team looked at the genetic code that controls stickleback pigmentation. In 2007, scientists found that in different stickleback populations around the world, changes in pigmentation are triggered by the same gene.

Interestingly, this gene turned out to be not at all unique to the small fish.

In humans and fish, pigmentation is controlled by a single gene.

Variations of this region of the gene, called Kit ligand, are associated with differences in skin color in humans. Kingsley discovered that in both fish and humans, genetic changes associated with pigmentation occur in regulatory elements of the genome.

But tracking specific regulatory elements across a huge genome is like looking for a needle in a haystack. Kingsley says they had a choice about which area to focus on.

In addition to encoding proteins for pigment cells, the Kit ligand region has many other functions. For example, it affects the behavior of blood stem cells, sperm and egg precursors, and intestinal neurons.

Scientists tried to isolate regulatory changes in this region that are responsible specifically for hair color, without affecting other functions of the gene. To do this, one of the team's experts, Catherine Guenther, cut segments of human DNA in the specified region and linked each piece of the regulatory gene to a reporter gene. If the genes were linked “correctly,” the scientists obtained a deep blue color.

Upon further study of the DNA in this regulatory segment, the team discovered that a single letter of the genetic code differs among people who have different hair colors.

This was confirmed in experiments with cell cultures. The switch to light hair color corresponded to a simple decrease in gene activity by 20% - allowing the scientists to conclude that they had found exactly the right key component of the DNA sequence.

The experiment was also successful in mice. Rodents in which scientists activated this gene in different ways resulted in either dark or light coat color.

Kingsley explained the results: “We can confidently say that one base pair is enough to lighten the fur of an animal, and all it takes is a reduction in gene expression by 20%. This is a good example of how finely tuned regulatory mechanisms can produce different traits in an organism. The genetic mechanism that controls hair lightening does not in any way disrupt the biology of other parts of the body. Blonde hair is just blonde hair."

Kingsley hopes that their work will not only lead to a better understanding of the molecular mechanisms of human diversity, but will be an important step towards increasing people's resistance to various diseases.

An international team of scientists has discovered more than a hundred new genetic loci that control color in Europeans. Despite the fact that these variants explain only 20% of the total contribution of genes to hair color, in total they have some predictive ability, thanks to which we can guess the hair color of their owner. The study was published in Nature Genetics.

Human hair color (as well as the color of the skin and iris of the eyes) is determined by the ratio of two types of melanin pigment - black-brown eumelanin and red-yellow pheomelanin. Pigments are synthesized from the amino acid tyrosine in specialized cells - melanocytes, located in the hair follicles.

It is known that the choice of biosynthesis of one or another type of melanin by cells is determined by the activity of the melanocortin 1 receptor, which is located on the surface of melanocytes and encoded by the MC1R gene. Polymorphisms in this gene—in particular, some variants that produce an inactive receptor—are associated with red hair color.

In a new study, an international team of scientists from the UK, Australia, Italy, the Netherlands, China and the US, including 23andMe employees, led by Timothy Spector of King's College London, discovered 124 genetic loci associated with human hair color. One of these loci turned out to be associated with the X chromosome. Most of the identified associations (111 out of 124) turned out to be new, previously unknown.

The genetic variants were found through a meta-analysis of two huge samples, together including almost 300 thousand participants of European descent. Data on half of the participants was provided by the American private genetic testing company 23andMe. The second half of the data was taken from the UK Biobank database, which includes information on health indicators and genotype of a significant number of people in the UK. Participants self-reported information about their natural hair color.

In addition to already known polymorphisms associated with pigmentation, such as in the MC1R, HERC2, IRF4 and SLC45A genes, the researchers showed a significant association with hair color with variants in regulatory genes encoding transcription factors, such as FOXO and SOX. A new locus associated with hair color was discovered on the X chromosome in the region of the COL46A gene, which encodes one of the types of collagen. Overall, the authors concluded that the main contribution to hair color is made by polymorphisms in regulatory genes, and not in genes directly related to pigmentation. In total, the polymorphisms found explained only 20% of the cases of heritability of hair color, about 35% of the heritability of red hair color, 25% for blond hair and 26% for black hair.

As a result of data analysis, scientists concluded that hair color is to some extent associated with a person’s gender - namely, women are characterized by lighter shades of hair.

The researchers also tested the predictive power of the associations they found using a mathematical model. It turned out that the model predicts black and red hair color with good probability, but for blondes and brown-haired people the predictions turned out to be less accurate.

Follow on

A person's appearance is largely determined by the color of his skin and hair. It is not surprising that scientists have long been busy with their evolution.

Over the past six years, studies of the genomes of thousands of people have identified at least eight sections of DNA that contain code elements unique to blondes. Thus, a certain single nucleotide polymorphism (SNP) was discovered in the genes responsible for the production of pigments, in particular melanin. Such mutations simultaneously change skin and hair color. In addition, variations of individual nucleotides occur outside genes, in areas involved in the regulation of DNA. Such mutations control how genes work in specific parts of the body, so they can change hair color without affecting skin characteristics.

Northern Europeans, who are predominantly blond, have the KITLG gene, changes in which are closely related to hair color. This gene encodes a protein that is responsible for the correct arrangement and specialization of cells in the body. David Kingsley from Stanford University has long been studying such SNPs. He and his colleagues discovered that this gene was responsible for the change in coloration of stickleback fish when they became isolated in freshwater lakes after the retreat of glaciers. Each individual population evolved independently of the others, becoming darker or lighter depending on the clarity of the water.

Kingsley's team hypothesized that the same changes could affect hair color in humans. First, scientists familiarized themselves in detail with the nucleotide sequence of the KITLG gene, obtained from residents of Iceland and the Netherlands, and noted all the SNPs that could affect hair color.

Then, for each case of polymorphism, they created two versions of the gene, one of which retained the original letter of the code, and the other of which replaced it with the “opposite” nucleotide (adenine to guanine). These genes were put into mouse cells. The results showed that such spot changes did not change the color of the coat from gray to white, but did noticeably lighten the color.

Experiments with human cells grown in the laboratory showed that SNPs do not turn the gene on or off, but only reduce its activity within 20%. However, this is enough for the hair color to change to a lighter or darker direction. In other words, changing just one specific nucleotide in the DNA performs the functions of fine-tuning the shade.

Another important conclusion made by the authors of the article, published in Nature Genetics, is that the mutations responsible for blond hair color are not genetically linked to other human characteristics.

Thus, from a genetic point of view, all stereotypes about blondes are not confirmed, which cannot be said about some other variations. For example, it is known that genetic changes in red-haired people affect the structure of proteins and have an impact on the entire body.

Scientists have found that golden hair appears due to a small mutation

For thousands of years, blondes have been an object of admiration and, more recently, ridicule. But a recent study showed that golden hair certainly has nothing to do with intelligence: it was the result of a small genetic mutation, when out of the 3 billion letters of the human genetic code, one letter "A" was replaced by the letter "G", reports National Geographic.

"The mutation is the biological mechanism that led to the natural appearance of blond hair," said Stanford University evolutionary biologist David Kingsley, who led the study. “In biology, this is a clear example of how a person’s external traits can be controlled.”

Kingsley is confident that the results of his latest research, published in the scientific journal Nature Genetics, shed light on the activities of the human genome. The mutation does not affect protein production in any of the 20,000 genes in the human genome. Among Caucasians, fair hair results from a mystical “turn of the switch” by 20%, which controls the signal gene in the hair follicles of the skin.

This signaling gene is involved in the formation of blood, eggs, sperm and stem cells. Turning such a gene on or off completely can be detrimental. However, a small mutation that affects the activity of a gene in only one area (for example, the skin) is not dangerous.

Harvard University biological engineer Pardis Sabeti, who was not involved in the study, said the study was a "beautiful demonstration" of the effects of the mutation, which had previously been little studied. Finding the change in one letter and proving that it is responsible for blond hair is a major scientific achievement.

Small change with big consequences

To find the genetic mutation responsible for blond hair, Kingsley and a team of scientists studied residents of Iceland and the Netherlands who had the corresponding genome. They painstakingly searched for the letter change responsible for the person's blond hair.

Scientists have studied the effects of changing the “letter” in a human skin cell grown in a Petri dish. A decrease in the activity of the “switch” that controls the signaling gene was found in the cells. A team of scientists led by Kingsley managed to breed groups of mice, both mutated and normal. When one “letter” was changed, the mice did not become white, but their fur became lighter than that of their relatives.

Learning the basics of something as simple and obvious as hair color will allow us to learn more about gene activity in other areas - such as diseases, where the stakes are higher, Kingsley says: "Understanding these basics will help people... who need drugs."

Harvard University genetics professor Hopi Hoekstra said the new discovery confirms scientists' assumptions: small changes in gene expression after changing just one pair of DNA bases can have a significant impact on external features.

Hair color "is a big starting point towards this type of molecular dissection" because changes in appearance make the effects of the mutation easy to see, she said. could be clearly measured."

The mutation that causes blonde hair, or any other, is not genetically linked to other traits, not even eye color, Kingsley said, challenging stereotypes about blondes. However, it is known that human mutations responsible for red hair color affect the protein structure of genes and lead to changes throughout the body. Red hair, light skin color and eyes go along with and are even genetically combined with, for example, greater sensitivity to pain and temperature changes, but a passionate character is already formed on its own.