MC1R gene - Genetics Home Reference MC1R gene Normal Function The MC1R gene provides instructions for making a protein called the melanocortin 1 receptor. This receptor plays an important role in normal pigmentation. The receptor is primarily located on the surface of melanocytes, which are specialized cells that produce a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. Melanin is also found in the light-sensitive tissue at the back of the eye (the retina), where it plays a role in normal vision. Melanocytes make two forms of melanin, eumelanin and pheomelanin. The relative amounts of these two pigments help determine the color of a person's hair and skin. People who produce mostly eumelanin tend to have brown or black hair and dark skin that tans easily. Eumelanin also protects skin from damage caused by ultraviolet (UV) radiation in sunlight. People who produce mostly pheomelanin tend to have red or blond hair, freckles, and light-colored skin that tans poorly.

Because pheomelanin does not protect skin from UV radiation, people with more pheomelanin have an increased risk of skin damage caused by sun exposure. The melanocortin 1 receptor controls which type of melanin is produced by melanocytes. When the receptor is activated, it triggers a series of chemical reactions inside melanocytes that stimulate these cells to make eumelanin. If the receptor is not activated or is blocked, melanocytes make pheomelanin instead of eumelanin. Common variations (polymorphisms) in the MC1R gene are associated with normal differences in skin and hair color. Certain genetic variations are most common in people with red hair, fair skin, freckles, and an increased sensitivity to sun exposure. These MC1R polymorphisms reduce the ability of the melanocortin 1 receptor to stimulate eumelanin production, causing melanocytes to make mostly pheomelanin. Although MC1R is a key gene in normal human pigmentation, researchers believe that the effects of other genes also contribute to a person's hair and skin coloring.

The melanocortin 1 receptor is also active in cells other than melanocytes, including cells involved in the body's immune and inflammatory responses. The receptor's function in these cells is unknown. Related Information The genetic causes, ethnic origins and history of red hair - Eupedia Eupedia Home > Genetics > The origins of red hair The genetic causes, ethnic origins and history of red hair Contents 7. Red hair and the Indo-European migrations What causes red hair ? Red hair is a recessive genetic trait caused by a series of mutations in the melanocortin 1 receptor (MC1R), a gene located on chromosome 16. As a recessive trait it must be inherited from both parents to cause the hair to become red. Consequently there are far more people carrying the mutation for red hair than people actually having red hair. In Scotland, approximately 13% of the population are redheads, although 40% carry at least one mutation. There are many kinds of red hair, some fairer, or mixed with blond ('strawberry blond'), some darker, like auburn hair, which is brown hair with a reddish tint.

This is because some people only carry one or a few of the several possible MC1R mutations. The lightness of the hair ultimately depends on other mutations regulating the general pigmentation of both the skin and hair. Red Hair Facts Skin and hair pigmentation is caused by two different kinds of melanin: eumelanin and pheomelanin. The most common is eumelanin, a brown-black polymer responsible for dark hair and skin, and the tanning of light skin. Pheomelanin has a pink to red hue and is present in lips, nipples, and genitals. The mutations in the MC1R gene imparts the hair and skin more pheomelanin than eumelanin, causing both red hair and freckles. Redheads have very fair skin, almost always lighter than non-redheads. This is an advantage in northern latitudes and very rainy countries, where sunlight is sparse, as lighter skin improves the absorption of sunlight, which is vital for the production of vitamin D by the body. The drawback is that it confers redheads a higher risk for both sunburns and skin cancer.

Studies have demonstrated that people with red hair are more sensitive to thermal pain and also require greater amounts of anesthetic than people with other hair colours. The reason is that redheads have a mutation in a hormone receptor that can apparently respond to at least two different hormones: the melanocyte-stimulating hormone (for pigmentation) and endorphins (the pain relieving hormone). Folk wisdom has long described redheads as hot-tempered and short-tempered. If you did an autosomal DNA test (e.g. with 23andMe), you can check if you carry some of the MC1R mutations . Red hair, a Celto-Germanic trait ? Red hair has long been associated with Celtic people. Both the ancient Greeks and Romans described the Celts as redheads. The Romans extended the description to Germanic people, at least those they most frequently encountered in southern and western Germany. It still holds true today. Although red hair is an almost exclusively northern and central European phenomenon, isolated cases have also been found in the Middle East, Central Asia (notably among the Tajiks), as well as in some of the Tarim mummies from Xinjiang, in north-western China.

The Udmurts, an Uralic tribe living in the northern Volga basin of Russia, between Kazan and Perm, are the only non-Western Europeans to have a high incidence of red hair (over 10%). So what do all these people have in common ? Surely the Udmurts and Tajiks aren't Celts, nor Germans. Yet, as we will see, all these people share a common ancestry that can be traced back to a single Y-chromosomal haplogroup: R1b. Where is red hair more common ? It is hard to calculate the exact percentage of the population having red hair as it depends on how wide a definition one adopts. For example, should men with just partial red beards, but no red hair on the top of their heads be included or not ? Should strawberry blond be counted as red, blond, or both ? Regardless of the definition, the frequency of red hair is highest in Ireland (10 to 30%) and Scotland (10 to 25%), followed by Wales (10 to 15%), Cornwall and western England, Brittany, the Franco-Belgian border, then western Switzerland, Jutland and southwest Norway.

The southern and eastern boundaries, beyond which red hair only occurs in less than 1% of the population, are northern Spain, central Italy, Austria, western Bohemia, western Poland, Baltic countries and Finland. Overall, the distribution of red hair matches remarkably well the ancient Celtic and Germanic worlds. It is undeniable too that the highest frequencies are always observed in Celtic areas, especially in those that remained Celtic-speaking to this day or until recently. The question that inevitably comes to many people's minds is: did red hair originate with the Celtic or the Germanic people ? Southwest Norway may well be the clue to the origin of red hair. It has been discovered recently, thanks to genetic genealogy, that the higher incidence of both dark hair and red hair (as opposed to blond) in southwest Norway coincided with a higher percentage of the paternal lineage known as haplogroup R1b-L21 , including its subclade R1b-M222, typical of northwestern Ireland and Scotland (the so-called lineage of Niall of the Nine Hostages ). It is now almost certain that native Irish and Scottish Celts were taken (probably as slaves) to southwest Norway by the Vikings, and that they increased the frequency of red hair there.

Map of red hair frequency in Europe Map of Y-haplogroup R1b in Europe The 45th parallel, a natural boundary for red hair? What is immediately apparent to genetic genealogists is that the map of red hair correlates with the frequency of haplogroup R1b in northern and western Europe. It doesn't really correlate with the percentage of R1b in southern Europe, for the simple reason that red hair is more visible among people carrying various other genes involved in light skin and hair pigmentation. Mediterranean people have considerably darker pigmentations (higher eumelanin), especially as far as hair is considered, giving the red hair alleles little opportunity to express themselves. The reddish tinge is always concealed by black hair, and rarely visible in dark brown hair. Rufosity being recessive, it can easily stay hidden if the alleles are too dispersed in the gene pool, and that the chances of both parents carrying an allele becomes too low. Furthermore, natural selection also progressively pruned red hair from the Mediterranean populations, because the higher amount of sunlight and strong UV rays in the region was more likely to cause potentially fatal melanoma in fair-skinned redheads.

At equal latitude, the frequency of red hair correlates amazingly well with the percentage of R1b lineages. The 45th parallel north, running through central France, northern Italy and Croatia, appears to be a major natural boundary for red hair frequencies. Under the 45th parallel, the UV rays become so strong that it is no longer an advantage to have red hair and very fair skin. Under the 41th parallel, redheads become extremely rare, even in high R1b areas. The 45th parallel is also the traditional boundary between northern European cultures, where cuisine is butter-based, and southern European cultures, preferring olive oil for cooking. In France, the 45th parallel is the also limit between the northern Oï¿½l dialects of French and the southern Occitan language. In northern Italy, it is the 46th parallel that separates German speakers (in South Tyrol) from Italian speakers. The natural boundary probably has a lot to do with the sun and climate in general, since the 45th parallel is exactly halfway between the Equator and the North Pole.

Even as far back as Neolithic times, the 45th parallel roughly divided the Mediterranean Cardium Pottery culture from the Central European Linear Pottery culture . It is entirely possible, and even likely, that the European north-south divide, not just for culture and agriculture, but also for phenotypes and skin pigmentation, go back to Neolithic times, when the southern expansion of agriculture was carried out mostly by the migration of farmers from the Near East to Iberia, following the Mediterranean coastlines, while the northern Danubian diffusion of farming was achieved by native Mesolithic Europeans who acquired Neolithic techniques by contact with farmers from Thessaly and Albania (Sesklo culture), and only blending to a small extent. Slavic, Baltic and Finnish people are predominantly descended from haplogroup R1a , N1c1 and I1 . Their limited R1b ancestry means that the MC1R mutation is much rarer in these populations. This is why, despite their light skin and hair pigmentation and living at the same latitude as Northwest Europeans, almost none of them have red hair, apart from a few Poles or Czechs with partial German ancestry. Where did red hair first arise ?

It has been suggested that red hair could have originated in Paleolithic Europe, especially since Neanderthal also had red hair. The only Neanderthal specimen tested so far (from Croatia) did not carry the same MC1R mutation responsible for red hair in modern humans (the mutation in question in known as Arg307Gly). But since Neanderthals evolved alongside Homo Sapiens for 600,000 years, and had numerous subspecies across all Europe, the Middle East and Central Asia, it cannot be ruled out that one particular subspecies of Neanderthal passed on the MC1R mutation to Homo Sapiens. It is however unlikely that this happened in Europe, because red hair is conspicuously absent from, or very low in parts of Europe with the highest percentages of haplogroup I (e.g. Finland, Bosnia, Sardinia) and R1a (Eastern Europe), the only two lineage associated with Mesolithic and Paleolithic Europeans. We must therefore look for the source of red hair, elsewhere. unsurpisingly, the answer lies with the R1b people - thought to have recolonised Central and Western Europe during the Bronze Age.

The origins of haplogroup R1b are complex, and shrouded in controversy to this day. The present author favours the theory of a Middle Eastern origin (a point upon which very few population geneticists disagree) followed by a migration to the North Caucasus and Pontic Steppe, serving as a starting point for a Bronze-age invasion of the Balkans, then Central and Western Europe. This theory also happens to be the only one that explains the presence of red hair among the Udmurts, Central Asians and Tarim mummies. A possible Neanderthal link ? Haplogroup R1b probably split from R1a during the Upper Paleolithic, roughly 25,000 years ago. The most likely location was Central Asia, around what is now the Caspian Sea, which only became a sea after the last Ice Age ended and the ice caps over western Russia melted. After the formation of the Caspian Sea, these nomadic hunter-gatherers, ended up on the greener and richer Caucaso-Anatolian side of the Caspian, where they may have domesticated local animals, such as cows, pigs, goats and sheep.

If the mutation for red hair was inherited from Neanderthal, it would have been from a Central Asian Neanderthal, perhaps from modern Uzbekistan, or an East Anatolian/Mesopotamian one. The mutation probably passed on to some other (extinct ?) lineages for a few millennia, before being inherited by the R1b tribe. Otherwise, it could also have arisen independently among R1b people as late as the Neolithic period (but no later). Red hair and the Indo-European migrations Developing pottery, or more probably acquiring the skills from Middle Eastern neighbours (notably haplogroup G2a ), part of the R1b tribe (and a small minority of G2a3b1) migrated across the Caucasus to take advantage of the vast expanses of grassland for their herds. This is where the Proto-Indo-European culture would have emerged, and spread to the native R1a tribes of the Eurasian steppe, with whom the R1b people blendeded to a moderate level (the reason why there is always a minority of R1b and G2a among predominantly R1a populations today, anywhere from Eastern Europe to Siberia and India).

The domestication of the horse in the Volga-Ural region circa 4000-3500 BCE, combined with the emergence of Bronze Age technology in the North Caucasus around 3300 BCE, would lead to the spectacular expansion of R1b and R1a lineages, an adventure that would lead these Proto-Indo-European speakers to the Atlantic fringe of Europe to the west, to Siberia and North America to the east, and all the way from Egypt to India to the south. From 3500 BCE, the vast majority of the R1b migrated westward along the Black Sea coast, to the metal-rich Balkans, where they mixed with the local inhabitants of Chalcolithic "Old Europe". A small number of R1b accompanied R1a to Siberia and Central Asia, which is why red hair very occasionally turns up in R1a-dominant populations of those areas (who usually still have a minority of R1b among their lineages, although some tribes may have lost them due to the founder effect ).

The archeological record indicates that this sustained series of invasions was extremely violent and led to the complete destruction of the until then flourishing civilizations of the Balkans and Carpathians (whose descendants survive as the I2a1b and E1b1b1a lineages). The R1b invaders took local women as wives and concubines, creating a new mixed ethnicity. The language evolved in consequence, adopting loanwords from the languages of Old Europe. This new ethnic and linguistic entity could be referred to as the Proto-Italo-Celto-Germanic people. After nearly a millennium in the Danubian basin (as far west as Bavaria), they would continue their westward expansion (from 2500 BCE) to Western Europe. In fact, the westward expansion was most likely carried out exclusively by the westernmost faction of R1b, who had settled north of the Alps, around Austria and Bavaria, and developed the Unetice culture.

Many R1b lineages stayed behind in the Balkans, where they progressively blended with the natives, then with later immigrants to the region (notably J2, under the Greek, Roman, Byzantine and Ottoman rules) over the next millennia - mostly losing their red hair due to the high incidence of very dark hair in the region today. According to ancient Greek writers, red hair was common among the Thracians, who lived around modern Bulgaria, an region where rufosity has almost completely disappeared today. Red hair alleles may have survived in the local gene pool though, but cannot be expressed due to the lack of other genes for light hair pigmentation. The red-haired Proto-Italic, Proto-Celtic and Proto-Germanic split in three branches during the progressive expansion of the successive Bronze-age Unetice, Tumulus and Urnfield cultures from Central Europe. The Proto-Germanic branch, originating as the R1b-U106 subclade , is thought to have migrated from present-day Austria to the Low Countries and north-western Germany.

They would continue their expansion (probably from 1200 BCE) to Denmark, southern Sweden and southern Norway, where, after blending with the local I1 and R1a people, the ancient Germanic culture emerged. Nowadays, the frequency of red hair among Germanic people is highest in the Netherlands, Belgium, north-western Germany and Jutland, i.e. where the percentage of R1b is the highest, and presumably the first region to be settled by R1b, before blending with the blond-haired R1a and I1 people from Scandinavia and re-expanding south to Germany during the Iron Age, with a considerably lower percentage of R1b and red-hair alleles. Red-haired is therefore most associated with the continental West Germanic peoples, and least with Scandinavians and Germanic tribes that originated in Sweden, like the Goths and the Vandals. This also explains why the Anglo-Saxon settlements on southern England have a higher frequency of redheads than the Scandinavian settlements of northeast England. The Italic branch crossed the Alps around 1300 BCE and settled across most of the peninsula, but especially in Central Italy (Umbrians, Latins, Oscans).

They probably belonged predominantly to the R1b-U152 subclade . It is likely that the original Italics had just as much red hair as the Celts and Germans, but lost them progressively as they intermarried with their dark-haired neighbours, like the Etruscans. The subsequent Gaulish Celtic settlements in northern Italy increased the rufosity in areas that had priorly been non-Indo-European (Ligurian, Etruscan, Rhaetic) and therefore dark-haired. Nowadays red hair is about as common in northern and in central Italy. The Celtic branch is the largest and most complex. The area that was Celtic-speaking in Classical times encompassed regions belonging to several distinct subclades of R1b-S116 (the Proto-Italo-Celtic haplogroup). The earliest migration of R1b to Western Europe must have happened with the diffusion of the Bronze Age to France, Belgium, Britain and Ireland around 2100 BCE - a migration best associated with the R1b-L21 subclade . A second migration took place around 1800 BCE to Southwest France and Iberia, and is associated with R1b-Z196.

These two branches are usually considered as Celtic, but was probably more distinct than the later continental Celtic were from Italic languages, due to its earlier split. The Northwest Celtic branch could have been ancestral to Goidelic languages (Gaelic), and the south-western one to Celtiberian. Both belong to the Q-Celtic group, as opposed to the P-Celtic group, to which Gaulish and Brythonic belong and which is associated with the expansion of the Hallstatt and La Tï¿½ne cultures and R1b-U152 (the same subclade as the Italic branch). Nowadays, red hair is found in all three Celtic branches, although it is most common in the R1b-L21 branch. The reason is simply that it is the northernmost branch (red hair being more useful at higher latitudes) and that the Celtic populations of Britain and Ireland have retained the purest Proto-Celtic ancestry (extremely high percentage of R1b).

Red hair was also found among the tartan-wearing Chï¿½rchï¿½n man, one of the Tarim mummies dating from 1000 BCE, who according to the author were an offshoot of Central European Celts responsible for the presence of R1b among modern Uyghurs. The earlier, non-tartan-wearing Tarim mummies from 2000 BCE, which were DNA tested and identified as members of haplogroup R1a, did not have red hair, just like modern R1a-dominant populations. Eupedia The Genetics of Red Hair: What Causes Natural Red Hair? written by: Paul Arnold •edited by: Paul Arnold •updated: 9/4/2009 Red hair is the rarest natural colour amongst humans. The colouring is due to mutations on a gene known as MC1R. This article looks at the genetic and biological roots of red hair. slide 1 of 6 What Causes Natural Red Hair? Skin and hair colour are determined by a pigment known as melanin. There are two main categories; eumelanin which is brown-black and phaeomelanin which is a sort of reddish brown.

A person with red hair will have much greater amounts of phaeomelanin than they will have of eumelanin. So what determines the difference? slide 2 of 6 It's All in the Genes The answers came to scientists in the late 1990's. The focus of their studies was chromosome 16 and in particular one of its genes, MC1R. Now the job of MC1R is to make a protein called MC1R receptor (melanocortin 1). This protein plays a key role in the conversion of phaeomelanin to eumelanin. When there are two mutated versions of the MC1R gene, the conversions are not as frequent and so there is a build up of phaeomelanin in the pigment cells. Consequently a person will have red hair and fair skin, they are also prone to freckles . slide 3 of 6 To understand why this happens we need to cover some basic genetics. You inherit two copies of every gene from your parents, one from your mother and one from your father. So you have two copies of the MC1R gene.

If both are mutated in the same way, the respective individual is likely to have red hair. slide 4 of 6 Inheriting Traits Of course many people wonder how a child with red hair can be born to parents who are brunette or blonde . That too can be explained by simple genetics, and a pattern of inheritance known as autosomal recessive. The parents will both have a functioning and a mutant version of the MC1R gene. They are said to be carriers and there is a 1 in 4 chance of them having a child who is a redhead. That's the probability that the mutant versions from both parents will come together in the next generation. It doesn't of course mean that if a couple have four kids, one of them will have a child with ginger hair. Odds and probabilities do not work like that. They are not reliant on what went before. It means that each child has a 25% chance of having red hair. slide 5 of 6 Medical Implications There is much more to this subject than its curiosity factor. There appear to be medical implications for people with red hair. Although here, like many areas of science, the research is contradictory.

In 2002 researchers from Louisville University showed that redheads are more sensitive to pain, and need more anaesthetic during surgery than people with blonde or dark hair. However, in 2005 scientists from the University of Edinburgh found that a MC1R mutation gives redheads a higher tolerance for pain. Research into these aspects of red hair genetics continues. Redheads should though be more careful about their exposure to sunlight as they are at an increased risk of contracting skin cancer. One theory suggests that melanin, the pigment responsible for tanning (it darkens as a protective mechanism) may be chemically different from the melanin of people with dark hair. Researchers have found that UV rays interact with phaeomelanin, creating molecules that cause damage to DNA, which can lead to cancer . If you are a redhead, the advice is not to stay out of the sun, but to be careful about how much exposure you get, and to cover yourself with a high factor sunscreen.

slide 6 of 6 Red Hair: A Mutation, A Royal Trait, and Sometimes a Curse | Red Hair Red Hair: A Mutation, A Royal Trait, and Sometimes a Curse Download Description Red Hair: A Mutation, A Royal Trait, and Sometimes a Curse by Aminah Sheikh Supervised by Dr. Rashid Alam Red Hair: A Mutation, A Royal Trait, and Sometimes a Curse by Aminah Sheikh Genetics and Pain - Do redheads need extra anesthesia? | HowStuffWorks Do redheads need extra anesthesia? George Doyle/ Getty Images It's something of a scary thought, but medical science is not totally sure exactly how anesthesia works. But the University of Louisville study has pulled back the curtain a bit on the mysterious inner workings of the higher brain . If redheads need more anesthesia than non-redheads, it probably has something to do with their genetic makeup. Luckily, geneticists have already figured out which gene is causing the anomaly. The melanocortin-1 receptor (MC1R) gene is responsible for the production of pigments in the body. Redheads' bodies produce the red pigment pheomelanin in increased amounts, and underproduce the dark pigment eumelanin.

It's because of the levels of these pigments that redheads have red hair and their skin doesn't tan well. Up Next The Healthy Things That Aren't Quiz Beyond this, scientists can only speculate why the gene may have an effect on pain . One explanation could be that the MC1R gene is also involved in hormones that stimulate pain receptors in the brain. The same mutation that inhibits the production of one pigment and increases another could also overproduce a pain-related hormone, making redheads more sensitive to pain. Another explanation suggests that the pigments themselves cause an increase in pain sensitivity. With the MC1R gene not functioning properly, the melanin doesn't have a receptor site to bind with. The pigments may seek other, similar receptors to bind to, such as the brain's pain receptors. The poor fit between the pain receptor and the pigment could overstimulate the brain's pain response, accounting for the increased need for anesthesia. Researchers also found a link between this gene and increased sensitivity to pain in studies of mice. Lab mice with a mutated MC1R gene -- and a lighter fur color -- require more anesthesia to prevent pain than mice with a properly functioning MC1R gene.

So while geneticists are confident that the MC1R gene is directly related to pain, it's the space in between point A and point B that requires filling in. The University of Louisville study provided the first demonstrable link between a phenotype (a visible genetic trait) and anesthesia. Since anesthesia's effects on the brain aren't fully understood, studying the role genes play in these higher functions could answer questions about which regions of the brain are responsible for these functions. It's also good news for another branch of medicine -- pharmacogenetics. This relatively recently created field studies how humans react differently to drugs, based on differences in their genes. Rather than simply using more general anesthesia to knock out a redhead -- and increase the risk of overdose -- future pharmacogenetic research may yield a totally separate anesthesia, one that's designed specifically for redheads. For more information on redheads, genetics, anesthesia and related topics, read the next page. Red Hair, Blue Eyes, and Other Genetic Mutations in Humans Follow Us Red Hair, Blue Eyes, and Other Genetic Mutations in Humans In any given species, the genetic makeup is uniform across a population. The attributes that differentiate one individual from another arise from variations in the genome. These variations are called genetic mutations.

These mutations may have a negative or positive effect depending on the gene that is altered. This Buzzle article provides an understanding of mutations and their effects. Advertisement Alike, yet unique! In humans, 99.9% of the genome is exactly the same in all individuals. The differences among the individuals arise due to variations in merely 0.1% of the whole genome. To understand what a genetic mutation is, one must first understand the concept of genes. A gene is a hereditary unit that consists of sequences of DNA that code for various molecules, which eventually help define an organism and regulate all processes associated with it. There are close to 30,000 genes in the human genome. Each gene consists of a juxtaposition of the four basic building blocks of DNA: Adenine (A), Guanine (G), Thymine (T), and Cytosine (C). These bases, present in various combinations, are responsible for coding all the various molecules that form an organism and help it function. Any alteration in the set sequence of a gene can be called a genetic mutation. The alteration may sometimes lead to a desirable change or to an undesirable change. In some cases, no change might be observed despite a genetic mutation.

Some Common Genetic Mutations in Humans Hair Color The color of human hair is a multifactorial trait that generally depends on the interaction between the eumelanin and pheomelanin pigments. These pigments are coded for by different forms of the MC1R gene. The expression of this gene, however, is controlled by various other genes. The melanocortin 1 receptor (MC1R) gene in its normal form produces pheomelanin and converts it into eumelanin. In the event of mutation, the amount of pheomelanin builds up, and is not converted into eumelanin. Pheomelanin produces colors from orange to yellow, while eumelanin is responsible for the black and brown pigments, and also for determining the darkness of the hair color. Blonde hair has a very low percentage of eumelanin, whereas brown hair has brown eumelanin in a large percentage. Black eumelanin leads to the presence of black hair. Pheomelanin is comparatively more stable, and hence breaks down very slowly when oxidized. As it decomposes, the color changes from red to orange to yellow, and finally to white.

The interactions between these pigments, and their presence in varying concentration lead to the occurrence of natural hair colors like black, brown, red, blonde, and white. Example: Red Hair In the case of red hair color, due to the malfunction of the MC1R gene, the pheomelanin in the hair follicles, builds up and is not converted into eumelanin. The stable and reddish nature of the pheomelanin molecules cause the resultant red hair color. The inheritance of red hair color depends on the hair color of the parents. If both parents are red-haired, then the progeny also has red hair. However, in cases where one parent has a different hair color, the non-mutated gene copy from that parent may correct or compensate for the mutated gene copy from the other parent, resulting in progeny that may or may not have red hair. Eye Color The color of the eyes is a physical trait of humans that is determined by more than one gene. All humans originally had brown eyes. Somewhere along the course of evolution, different eye colors emerged due to genetic mutations. Since then, these mutations have been passed down through generations.

A research paper in the Journal of Human Genetics provides evidence that close to 16 genes may be responsible for eye color, and the way these interact with each other determine the specific shade of color. However, the two main genes involved in this process are the OCA2 and the HERC2 genes located on chromosome 15. The OCA2 gene is responsible for production of melanin, a molecule that imparts color. The absence of this molecule leads to albinism. The HERC2 gene regulates the expression of the OCA2 gene. A specific mutation in the HERC2 gene along with single nucleotide polymorphisms (SNPs) in the OCA2 gene causes the development of a spectrum of different eye colors in humans. The condition of heterochromia, where the two eyes have different coloration, is also due to the interaction of the OCA2 and HERC2 genes. Example: Blue Eyes The occurrence of blue eyes is a recessive trait. The brown or black eye color is usually dominant over it. It is caused due to specific interactions between the OCA2 and HERC2 gene. The progeny only has blue eyes if both parents also have a blue eye color.

If one of the parents has a different eye color, that color is usually seen in the progeny. However, there have been rare cases reported where this recessive trait skipped generations in family lineages, often occurring in alternate generations, irrespective of the eye colors of the parents. Freckles While the occurrence of freckles is not dependent on genetic factors, their abundance is due to genetic mutations in the MC1R gene. Melanocytes are specialized cells in our skin, which produce the pigment melanin. Melanin protects our DNA from the harmful ultraviolet (UV) radiations given off by the sun. Generally melanocytes are evenly spread throughout the skin, causing the skin to tan due to melanin production. In individuals with mutated MC1R gene, these melanocytes are present in clumps across the skin, and on exposure to sunlight lead to the occurrence of freckles. Since the gene is mutated, the melanin produced exhibits a shade of red. Cleft Chin It is yet another example of multifactorial traits. Additionally, it also exhibits variable penetrance, which in simple words implies that this trait does not follow a strict pattern of inheritance.

If a parent has a cleft chin, the offspring may or may not exhibit the same. This is because this trait essentially occurs due to the incomplete fusion of the jawbone during the process of embryogenesis. Modifier genes may be activated during the process, leading to a correction of the error and causing the progeny to show the absence of the cleft. However, if those genes are not activated, the error remains uncorrected, and the fetus is born with a cleft chin. Double Eyelash This particular phenotype is also termed distichiasis. It is the condition where eyelids show presence of a double row of eyelashes. Hair follicles replace the oil glands present on the waterline along the eyelids. This occurs due to a mutation in the FOXC2 gene, which is responsible for most of the tissue development during embryogenesis. Extensive mutations in this gene may cause lymphedema and failure of the lymphatic system. Dimples This trait is exhibited when genetic defects lead to shortened facial muscles, and cause the formation of indentations when an individual smiles. The aberrant muscles are caused due to defects caused in the subcutaneous connective tissue during the course of development of the embryo.

The exact genetic cause for this is as yet unidentified, but geneticists believe that it may be a dominant trait caused due to a single gene mutation. The inheritance of this trait is variable. If both parents have this quality, then it is inherited by the child. But in the case of only one parent exhibiting dimples, the child may or may not show its presence. Types of Genetic Mutations Mutations may result from a damage to the genome (exogenous or endogenous), faulty repair of damaged DNA, insertion and deletion of individual bases or of short sequences of DNA, or from errors that have occurred during replication of the genome. They are classified and named based on the cause and effect of the mutation. Mutations Causing Structural Changes Point mutations: These mutations are characterized by changes in a single nucleotide in a gene. There are 4 types of point mutations: deamination, depurination, transition, and transversion. Deamination: This mutation arises when a base undergoes hydrolysis and the amine group is displaced from the base, transforming it into an atypical base with a keto group.

For example, deamination of cytosine would yield a uracil base and that of adenine will yield a hypoxanthine base. Depurination: This mutation occurs when there is loss of a purine base from a sequence, giving rise to an apurinic site. The purine bases are adenine and guanine. Transition: In this type of mutation, a purine base is replaced by another purine base or a pyrimidine base is replaced by another pyrimidine base. Adenine and guanine are purines, and pyrimidines include cytosine and thymine. Transversion: This mutation involves a purine being replaced by a pyrimidine and a pyrimidine replaced by a purine. This type of mutation is less common as compared to transition mutations. If these mutations occur in the coding regions of the genes, they are further classified based on the type of effect seen in the resultant molecule. They are of 4 types. Frame-shift mutations: Nucleotides are read by transcribed and translated by grouping them into groups of three, called codons. Each codon codes of a unique amino acid. The nucleotides are read as codons by the open reading frame.

In the event of a deletion or insertion, the grouping is disrupted and leads to a different grouping that shifts the reading frame, causing a frame-shift mutation. Silent Mutations: The altered base causes a change in the amino acid codon, but the amino acid remains the same despite the change. For example: the codon of the amino acid lysine is TTC, if due to a transition mutation the codon is changed to TTT, it will be a silent mutation as the codon TTT also coded for lysine. Missense mutations: The altered base causes the amino acid codon to change such that the codon now codes for a different amino acid. For example, if the lysine codon TTC is changed to TCC codon which codes for arginine, it will result in a missense mutation. Nonsense mutation: These mutations occur when the altered base changes the codon to a stop codon that terminates the amino acid chain and could lead to a truncated protein. For example, if the TTC lysine codon is changed to ATC stop codon, the protein synthesis machinery will terminate and lead to a incomplete protein. Insertions- The addition of extra nucleotides to a sequence is called an insertion mutation.

There can be an insertion of a single nucleotide, as well as a sequence of nucleotides. Such sequences are called transposable elements and they are characterized by their ability to change their position in the genome. Deletions- The removal of a single nucleotide or a sequence of nucleotides (transposable elements) is called a deletion mutation. Gene duplication- This occur when a multiple amplified copies of a gene are found, leading to overproduction of a molecule. Translocation- This involves the change in position of a set of genes from one chromosome to another non-homologous chromosome. Inversion- When the sequence of genes on a chromosome is disrupted and the sequence is reversed, the resulting change in orientation of genes is called an inversion. Loss of heterozygosity- Every gene occurs in a set of two copies. The two copies are called alleles of the gene. An individual may possess the identical alleles (homozygous) or two different alleles (heterozygous) of the same gene. When there is a loss of one allele of the gene in a heterozygous individual, the condition is called loss of heterozygosity.

Mutations Affecting Function Loss of function- If a mutation in the gene causes the gene to lose its normal function, the mutation is called a loss-of function mutation. In cancer, most tumor suppressor genes undergo this type of mutation. Gain of function- When a mutation in a gene leads to the gain of a new and abnormal function, that mutation is called a gain of function mutation. In cancer, the oncogenes undergo this mutation and start rapidly regenerating. Dominant negative mutation- In this type of gene mutation, the product of the altered allele of a gene acts as an antagonist towards the product of the normal wild-type allele of that same gene. The altered product does not let the normal product carry out its original function. This occurs in genes like p53, ATM, etc. Lethal mutation- When a mutation in a specific gene leads to a halt in the development or even death of an organism, that mutation is called a lethal mutation. Mutations Affecting Inheritance Pattern Heterozygous mutations- This occurs when there is a mutation in only one allele of the gene. Homozygous mutations- This involves the occurrence of the same mutations on both the alleles of a gene.

Compound heterozygous mutations- This condition arises when both alleles exhibit different mutations. These examples gives one an understanding of the complex and intricate nature of genetic mutations. While most of the mutations are harmless and responsible for the physical variation across a species, some mutations do cause life-altering health conditions. Scientists are still working hard to decipher the function of each particular gene and the interactions between them. Komal B. Patil

Question: A mutated MC1R gene causes what physical trait?
Answer: Red Hair