The melanocortin 1 receptor (MC1R), also known as melanocyte-stimulating hormone receptor (MSHR), melanin-activating peptide receptor, or melanotropin receptor, is a
G protein–coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
that binds to a class of
pituitary
In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The hypop ...
peptide hormone
Peptide hormones or protein hormones are hormones whose molecules are peptide, or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine system of animals, including h ...
s known as the
melanocortin
The melanocortins are a family of neuropeptide hormones which are the ligands of the melanocortin receptorsEricson, M.D., et al., ''Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016.'' Biochim Biophys Acta Mol Basi ...
s, which include
adrenocorticotropic hormone
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...
(ACTH) and the different forms of
melanocyte-stimulating hormone
The melanocyte-stimulating hormones, known collectively as MSH, also known as melanotropins or intermedins, are a family of peptide hormones and neuropeptides consisting of α-melanocyte-stimulating hormone (α-MSH), β-melanocyte-stimulating ...
(MSH). It is coupled to
Gαs and upregulates levels of
cAMP
Camp may refer to:
Outdoor accommodation and recreation
* Campsite or campground, a recreational outdoor sleeping and eating site
* a temporary settlement for nomads
* Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...
by activating
adenylyl cyclase
Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction:
:A ...
in cells expressing this receptor. It is normally expressed in skin and
melanocyte
Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea),
the inner ear,
vaginal epithelium, meninges,
bones,
and heart.
...
s, and to a lesser degree in
periaqueductal gray matter
The periaqueductal gray (PAG, also known as the central gray) is a brain region that plays a critical role in autonomic function, motivated behavior and behavioural responses to threatening stimuli. PAG is also the primary control center for d ...
,
astrocyte
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of e ...
s and
leukocyte
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
s.
In
skin cancer
Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...
, MC1R is highly expressed in
melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
s but not
carcinoma
Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal ...
s.
MC1R is one of the key
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s involved in regulating
mammalian
Mammals () are a group of vertebrate animals constituting the class (biology), class Mammalia (), characterized by the presence of mammary glands which in Female#Mammalian female, females produce milk for feeding (nursing) their young, a ...
skin color
Human skin color ranges from the darkest brown to the lightest hues. Differences in skin color among individuals is caused by variation in pigmentation, which is the result of genetics (inherited from one's biological parents and or individu ...
and
hair color
Human hair color is the pigmentation of human hair follicles due to two types of melanin: eumelanin and pheomelanin. Generally, if more melanin is present, the color of the hair is darker; if less melanin is present, the hair is lighter. The t ...
. It is located on the
plasma membrane of specialized
cells known as
melanocyte
Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea),
the inner ear,
vaginal epithelium, meninges,
bones,
and heart.
...
s, which produce the
pigment
A pigment is a colored material that is completely or nearly insoluble in water. In contrast, dyes are typically soluble, at least at some stage in their use. Generally dyes are often organic compounds whereas pigments are often inorganic compo ...
melanin
Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...
through the process of
melanogenesis
Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea),
the inner ear,
vaginal epithelium, meninges,
bones,
and heart.
...
. It works by controlling the type of melanin being produced, and its activation causes the melanocyte to switch from generating the yellow or red
phaeomelanin
Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...
by default to the brown or black
eumelanin
Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amin ...
in replacement.
MC1R has also been reported to be involved in cancer (independent of skin coloration), developmental processes, and susceptibility to infections and pain.
Functions
Coloration in mammals
The MC1R protein lies within the
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
, and is signalled by
melanocyte-stimulating hormone
The melanocyte-stimulating hormones, known collectively as MSH, also known as melanotropins or intermedins, are a family of peptide hormones and neuropeptides consisting of α-melanocyte-stimulating hormone (α-MSH), β-melanocyte-stimulating ...
(MSH) released by the
pituitary
In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The hypop ...
gland.
When activated by one of the variants of MSH, typically α-MSH, MC1R initiates a complex signaling cascade that leads to the production of the brown or black pigment eumelanin. In contrast, the receptor can also be antagonized by
agouti signalling peptide
Agouti-signaling protein is a protein that in humans is encoded by the ASIP gene. It is responsible for the distribution of melanin pigment in mammals. Agouti interacts with the melanocortin 1 receptor to determine whether the melanocyte (pigment ...
(ASIP), which reverts the cell back to producing the yellow or red phaeomelanin.
The pulsatile nature of ASIP signalling through MC1R produces the characteristic yellow and black agouti banding pattern observed on most mammalian hair. In some species, ASIP signaling is not of a pulsative nature, but is limited to certain regions. This is especially conspicuous in horses, where a
bay horse
Bay is a hair coat color of horses, characterized by a reddish-brown or brown body color with a black point coloration on the mane, tail, ear edges, and lower legs. Bay is one of the most common coat colors in many horse breeds.
The black ...
has black legs, mane, and tail, but a reddish body. A notable exception to this is human hair, which is neither banded nor particoloured, so is thought to be regulated by α-MSH signaling through MC1R exclusively.
In the United States, about 25% of the population carries the mutated melanocortin 1 receptor that causes red hair. With one in four people as carriers, the chance of two people having a child with red hair is about 2% (one in 64). The prevalence of
red hair
Red hair (also known as orange hair and ginger hair) is a hair color found in one to two percent of the human population, appearing with greater frequency (two to six percent) among people of Northern or Northwestern European ancestry and ...
varies considerably worldwide. People with freckles and no red hair have an 85% chance of carrying the MC1R gene that is connected to red hair. People with no freckles and no red hair have an 18% chance of carrying the MC1R gene linked to red hair.
Eight genes have been identified in humans that control whether the MC1R gene is turned on and the person has red hair.
Pain in mammals
In mutant yellow-orange mice and human redheads, both with nonfunctional MC1R, both genotypes display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to
morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
-metabolite
analgesic
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
s.
These observations suggest a role for mammalian MC1R outside the pigment cell, though the exact mechanism through which the protein can modulate pain sensation is not known.
In a certain genetic background in mice it has been reported that animals lacking MC1R had increased tolerance to
capsaicin
Capsaicin (8-methyl-''N''-vanillyl-6-nonenamide) ( or ) is an active component of chili peppers, which are plants belonging to the genus ''Capsicum''. It is a chemical irritant for mammals, including humans, and produces a sensation of burning ...
acting through the
TRPV1
The transient receptor potential cation channel subfamily V member 1 (TrpV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the ''TRPV1'' gene. It was the first isolated member of th ...
receptor and decreased response to chemically induced inflammatory pain.
Humans with MC1R mutations have been reported to need approximately 20% more
Inhalational anaesthetic than controls.
Lidocaine
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidoca ...
was reported to be much less effective in reducing pain in another study of humans with MC1R mutations
Some roles in development
Since
G protein–coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
s are known to activate
Signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
in cells, it should not be surprising to find MC1R involved in development. As one example at the cellular level, preventing signalling by MC1R stopped
erythropoiesis
Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' "to make") is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
It is stimulated by decrea ...
from proceeding from the polychromatic cell stage (poly-E in the figure) to the orthochromatic cell stage (ortho-E in the diagram). The same report showed that neutralizing
antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
to MC1R prevented phosphorylation of
STAT5 by
erythropoietin
Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bo ...
, and that MC2R and MC5R were also involved, as shown in their model.
![MCR1carti4TC](https://upload.wikimedia.org/wikipedia/commons/d/d8/MCR1carti4TC.jpg)
One example at the tissue level showed the involvement of MC1R in the normal and pathological development of
articular cartilage
Hyaline cartilage is the glass-like (hyaline) and translucent cartilage found on many joint surfaces. It is also most commonly found in the ribs, nose, larynx, and trachea. Hyaline cartilage is pearl-gray in color, with a firm consistency and has ...
in the mouse
knee
In humans and other primates, the knee joins the thigh with the leg and consists of two joints: one between the femur and tibia (tibiofemoral joint), and one between the femur and patella (patellofemoral joint). It is the largest joint in the hu ...
. In this study the authors compared normal mice with mice completely lacking MC1R. Even without experimental induction of osteoarthritis, mice without MC1R had less articular cartilage (as shown by the red staining in the image). After experimental induction of osteoarthritis, the defect caused by MC1R was more pronounced.
MC1R and infection/inflammation
The involvement of MC1R in a rat model of
Candida albicans
''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is us ...
vaginitis
Vaginitis, also known as vulvovaginitis, is inflammation of the vagina and vulva. Symptoms may include itching, burning, pain, discharge, and a bad smell. Certain types of vaginitis may result in complications during pregnancy.
The three main ...
was investigated. These authors suggest that MC1R is important in anti-fungal and anti-inflammatory processes, in part because
siRNA
Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA at first non-coding RNA molecules, typically 20-24 (normally 21) base pairs in length, similar to miRNA, and operating wi ...
knockdown of MC1R almost completely prevented the responses.
Nosocomial infections
A hospital-acquired infection, also known as a nosocomial infection (from the Greek , meaning "hospital"), is an infection that is acquired in a hospital or other health care facility. To emphasize both hospital and nonhospital settings, it is ...
are of variable importance. One of the most important is complicated
sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
, which was defined as sepsis with organ dysfunction. One variant of MC1R (MC1RR163Q, rs885479) was reported to be associated with lowered risk of developing complicated sepsis during hospitalization after trauma. Thus, if the association is confirmed, MC1R targeting may become a therapeutic option to prevent severe sepsis.
Role in cancer independent of skin color
MC1R signalling stimulates
antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
and
DNA repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...
pathways, as reviewed.
There are
single nucleotide polymorphisms
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
in MC1R that are associated with predisposition to nonmelanoma skin cancer. It has been reported that variants of MC1R, even in
heterozygotes
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mo ...
and independent of their effects on pigmentation, are risk factors for
basal cell carcinoma
Basal-cell carcinoma (BCC), also known as basal-cell cancer, is the most common type of skin cancer. It often appears as a painless raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raise ...
and
squamous cell carcinoma A review has discussed the role of some MC1R variants in
melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
and basal and squamous cell carcinomas independent of pigment production.
Role in kidney pathology
Membranous glomerulonephritis
Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly people between ages of 30 and 50 years, usually white people (i.e., those of European, Middle Eastern, or North African ancestry.).
It is the seco ...
is a serious human disease that can be treated with
ACTH
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...
, which is a known
agonist of MC1R. In a rat model of nephritis it was found that treatment with a different
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
of MC1R improved aspects of kidney morphology and reduced
proteinuria
Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...
,
which may help explain the benefit of ACTH in humans.
Ligands
Agonists
*
α-MSH
α-Melanocyte-stimulating hormone (α-MSH) is an endogenous peptide hormone and neuropeptide of the melanocortin family, with a tridecapeptide structure and the amino acid sequence Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. I ...
- nonselective peptide full agonist
*
β-MSH
β-Melanocyte-stimulating hormone (β-MSH) is an endogenous peptide hormone and neuropeptide. It is a melanocortin, specifically, one of the three types of melanocyte-stimulating hormone (MSH), and is produced from proopiomelanocortin (POMC). I ...
- nonselective peptide full agonist
*
γ-MSH - nonselective peptide full agonist
*
ACTH
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...
- nonselective peptide full agonist
*
Afamelanotide
Afamelanotide, sold under the brand name Scenesse, is a synthetic peptide and analogue of α-melanocyte stimulating hormone. It has been used to prevent skin damage from the sun in people with erythropoietic protoporphyria in the European Un ...
- nonselective peptide full agonist
*
BMS-470,539
BMS-470539 is a small-molecule experimental drug which acts as a potent and highly selective full agonist of the MC1 receptor. It was discovered in 2003 as part of an effort to understand the role of the MC1 receptor in immunomodulation, and ...
- selective small-molecule full agonist
*
Bremelanotide
Bremelanotide, sold under the brand name Vyleesi, is a medication used to treat low sexual desire in women. Specifically it is used for low sexual desire which occurs before menopause and is not due to medical problems, psychiatric problems, or ...
- nonselective peptide full agonist
*
Melanotan II
Melanotan II is a synthetic analogue of the peptide hormone α-melanocyte-stimulating hormone (α-MSH) that stimulates melanogenesis and increases sexual arousal.
It was under development as drug candidate for female sexual dysfunction and ...
- nonselective peptide full agonist
*
Modimelanotide
Modimelanotide (INN) (code names AP-214, ABT-719, ZP-1480) is a melanocortinergic peptide drug derived from α-melanocyte-stimulating hormone (α-MSH) which was under development by, at different times, Action Pharma, Abbott Laboratories, AbbVi ...
- nonselective peptide full agonist
*
Setmelanotide
Setmelanotide, sold under the brand name Imcivree, is a medication used for the treatment of genetic obesity caused by a rare single-gene mutation.
The most common side effects include injection site reactions, skin hyperpigmentation (skin patc ...
- nonselective peptide full agonist
Antagonists
*
Agouti signalling peptide
Agouti-signaling protein is a protein that in humans is encoded by the ASIP gene. It is responsible for the distribution of melanin pigment in mammals. Agouti interacts with the melanocortin 1 receptor to determine whether the melanocyte (pigment ...
- nonselective peptide antagonist
In other organisms
![Zfishchroma](https://upload.wikimedia.org/wikipedia/commons/6/67/Zfishchroma.jpg)
MC1R has a slightly different function in
cold-blooded animals such as fish, amphibians, and reptiles. Here, α-MSH activation of MC1R results in the dispersion of eumelanin-filled
melanosomes
A melanosome is an organelle found in animal cells and is the site for synthesis, storage and transport of melanin, the most common light-absorbing pigment found in the animal kingdom. Melanosomes are responsible for color and photoprotection ...
throughout the interior of pigment cells (called
melanophore
Chromatophores are cells that produce color, of which many types are pigment-containing cells, or groups of cells, found in a wide range of animals including amphibians, fish, reptiles, crustaceans and cephalopods. Mammals and birds, in cont ...
s). This gives the skin of the animal a darker hue and often occurs in response to changes in mood or environment. Such a physiological color change implicates MC1R as a key mediator of adaptive
cryptic coloration
Camouflage is the use of any combination of materials, coloration, or illumination for concealment, either by making animals or objects hard to see, or by disguising them as something else. Examples include the leopard's spotted coat, the b ...
. The role of ASIP's binding to MC1R in regulating this adaptation is unclear; however, in teleost fish at least, functional antagonism is provided by
melanin-concentrating hormone
Melanin-concentrating hormone (MCH), also known as pro-melanin stimulating hormone (PMCH), is a cyclic 19-amino acid orexigenic hypothalamic peptide originally isolated from the pituitary gland of teleost fish, where it controls skin pigmentation ...
. This signals through its receptor to aggregate the melanosomes toward a small area in the centre of the melanophore, resulting in the animal's having a lighter overall appearance.
Cephalopod
A cephalopod is any member of the molluscan class Cephalopoda (Greek plural , ; "head-feet") such as a squid, octopus, cuttlefish, or nautilus. These exclusively marine animals are characterized by bilateral body symmetry, a prominent head ...
s generate a similar, albeit more dramatic, pigmentary effect using muscles to rapidly stretch and relax their pigmented
chromatophore
Chromatophores are cells that produce color, of which many types are Biological pigment, pigment-containing cells, or groups of cells, found in a wide range of animals including amphibians, fish, reptiles, crustaceans and cephalopods. Mammals and ...
s. MC1R does not appear to play a role in the rapid and spectacular colour changes observed in these
invertebrate
Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...
s.
Pigmentation genetics
''MC1R''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
expression is regulated by the
microphthalmia-associated transcription factor (MITF).
Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s of the ''MC1R'' gene either can create a
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
that constantly signals, even when not stimulated, or can lower the receptor's activity.
Allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chro ...
s for constitutively active ''MC1R'' are inherited
dominantly and result in a black coat colour, whereas alleles for dysfunctional ''MC1R'' are
recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
and result in a light coat colour.
Variants of ''MC1R'' associated with black, red/yellow, and white/cream coat colors in numerous animal
species
In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
have been reported, including:
*
Laboratory mice
The laboratory mouse or lab mouse is a small mammal of the order Rodentia which is bred and used for scientific research or feeders for certain pets. Laboratory mice are usually of the species ''Mus musculus''. They are the most commonly used ...
*
Dog
The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. Do ...
s
*
Big cat
The term "big cat" is typically used to refer to any of the five living members of the genus '' Panthera'', namely the tiger, lion, jaguar, leopard, and snow leopard.
Despite enormous differences in size, various cat species are quite similar ...
s
*
Horses
The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 million yea ...
*
Cattle
Cattle (''Bos taurus'') are large, domesticated, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus ''Bos''. Adult females are referred to as cows and adult mal ...
*
Chicken
The chicken (''Gallus gallus domesticus'') is a domesticated junglefowl species, with attributes of wild species such as the grey and the Ceylon junglefowl that are originally from Southeastern Asia. Rooster or cock is a term for an adult m ...
s
*
Bananaquit
*
Gyrfalcon
The gyrfalcon ( or ) (), the largest of the falcon species, is a bird of prey. The abbreviation gyr is also used. It breeds on Arctic coasts and tundra, and the islands of northern North America and the Eurosiberian region. It is mainly a reside ...
*
Kermode bear
The Kermode bear, sometimes called the spirit bear (''Ursus americanus kermodei''), is a subspecies of the American black bear and lives in the Central and North Coast regions of British Columbia, Canada. It is the official provincial mammal ...
s
*
Rock pocket mice
*
Domestic rabbit
A domestic or domesticated rabbit (''Oryctolagus cuniculus domesticus'')—more commonly known as a pet rabbit, bunny, bun, or bunny rabbit—is a subspecies of European rabbit, a member of the lagomorph family. A male rabbit is known as a ''bu ...
s
*
Antarctic fur seal
The Antarctic fur seal (''Arctocephalus gazella''), is one of eight seals in the genus ''Arctocephalus'', and one of nine fur seals in the subfamily Arctocephalinae. Despite what its name suggests, the Antarctic fur seal is mostly distributed i ...
s
*
Mammoth
A mammoth is any species of the extinct elephantid genus ''Mammuthus'', one of the many genera that make up the order of trunked mammals called proboscideans. The various species of mammoth were commonly equipped with long, curved tusks and, ...
A study on unrelated British and Irish individuals demonstrated that over 80% of people with red hair and/or fair skin that tan poorly have a dysfunctional variant of the ''MC1R'' gene. This is compared to less than 20% in people with brown or black hair, and less than 4% in people showing a good tanning response.
Asp294His (rs1805009) is a
single nucleotide polymorphism
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
(SNP) in the ''
MC1R
The melanocortin 1 receptor (MC1R), also known as melanocyte-stimulating hormone receptor (MSHR), melanin-activating peptide receptor, or melanotropin receptor, is a G protein–coupled receptor that binds to a class of pituitary peptide hormones ...
''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
and it is associated with
red hair
Red hair (also known as orange hair and ginger hair) is a hair color found in one to two percent of the human population, appearing with greater frequency (two to six percent) among people of Northern or Northwestern European ancestry and ...
and light skin type.
Other SNPs in the gene,
Arg151Cys and
Arg160Trp, are also associated with red hair.
The
Out-of-Africa
In paleoanthropology, the recent African origin of modern humans, also called the "Out of Africa" theory (OOA), recent single-origin hypothesis (RSOH), replacement hypothesis, or recent African origin model (RAO), is the dominant model of the ...
model proposes that modern humans originated in Africa and migrated north to populate Europe and Asia. These migrants most likely had a functional ''MC1R'' variant and, accordingly, dark hair and skin as displayed by indigenous Africans today. As humans migrated north, the absence of high levels of
solar radiation
Solar irradiance is the power per unit area (surface power density) received from the Sun in the form of electromagnetic radiation in the wavelength range of the measuring instrument.
Solar irradiance is measured in watts per square metre ( ...
in northern Europe and Asia relaxed the
selective pressure
Any cause that reduces or increases reproductive success in a portion of a population potentially exerts evolutionary pressure, selective pressure or selection pressure, driving natural selection. It is a quantitative description of the amount of ...
on active ''MC1R'', allowing the gene to mutate into dysfunctional variants without reproductive penalty, then propagate by
genetic drift
Genetic drift, also known as allelic drift or the Wright effect, is the change in the frequency of an existing gene variant (allele) in a population due to random chance.
Genetic drift may cause gene variants to disappear completely and there ...
. Studies show the ''MC1R Arg163Gln'' allele has a high frequency in East Asia and may be part of the evolution of light skin in East Asian populations. No evidence is known for
positive selection
In population genetics, directional selection, is a mode of negative natural selection in which an extreme phenotype is favored over other phenotypes, causing the allele frequency to shift over time in the direction of that phenotype. Under dir ...
of ''MC1R'' alleles in Europe
and there is no evidence of an association between the emergence of dysfunctional variants of ''MC1R'' and the evolution of light skin in European populations. The lightening of skin color in Europeans and East Asians is an example of
convergent evolution
Convergent evolution is the independent evolution of similar features in species of different periods or epochs in time. Convergent evolution creates analogous structures that have similar form or function but were not present in the last com ...
.
See also
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Chromatophore
Chromatophores are cells that produce color, of which many types are Biological pigment, pigment-containing cells, or groups of cells, found in a wide range of animals including amphibians, fish, reptiles, crustaceans and cephalopods. Mammals and ...
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Melanocyte
Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea),
the inner ear,
vaginal epithelium, meninges,
bones,
and heart.
...
*
SLC24A5
SLC may refer to:
Places
* Salt Lake City, Utah
* Salt Lake City International Airport, IATA Airport Code
Education
* Sarah Lawrence College, NY
* School Leaving Certificate (Nepal)
* St. Lawrence College, Ontario, Canada
* Small Learning Comm ...
*
Melanin
Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...
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Pigment
A pigment is a colored material that is completely or nearly insoluble in water. In contrast, dyes are typically soluble, at least at some stage in their use. Generally dyes are often organic compounds whereas pigments are often inorganic compo ...
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Human skin color
Human skin color ranges from the darkest brown to the lightest hues. Differences in skin color among individuals is caused by variation in pigmentation, which is the result of genetics (inherited from one's biological parents and or individu ...
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Freckles
Freckles are clusters of concentrated melaninized cells which are most easily visible on people with a fair complexion. Freckles do not have an increased number of the melanin-producing cells, or melanocytes, but instead have melanocytes that ...
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Melanotropin receptor
References
Further reading
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External links
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{{DEFAULTSORT:Melanocortin 1 Receptor
G protein-coupled receptors
Human proteins
Hair color
Skin pigmentation
Mutated genes
Genes on human chromosome 16