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The agouti gene encodes the agouti signalling peptide (ASIP), a paracrine signaling molecule involved in red-black pigment type-switching. Agouti interacts with the melanocortin 1 receptor to determine whether the melanocyte (pigment cell) produces the yellow to red phaeomelanin, or the brown to black eumelanin. This interaction is responsible for making distinct light and dark bands in the hairs of animals such as the agouti. In other species such as horses, it determines what parts of the body are red or black.

There are two signalling molecules which compete to bind with melanocortin 1 receptor (MC1R) proteins, the agouti signalling peptide (ASIP) and the alpha-Melanocyte-stimulating hormone (α-MSH). Activation by α-MSH causes production of the darker eumelanin, while activation by ASIP causes production of the redder phaeomelanin.

In many species, successive pulses of ASIP block contact between α-MSH and MC1R, resulting in alternating production of eumelanin and pheomelanin; hairs are banded light and dark as a result. In other species, ASIP is regulated such that it only occurs in certain parts of the body. The light undersides of most mammals are due to the carefully controlled action of ASIP. Additionally, the Agouti locus is the site of mutations in several species that result in black-and-tan pigmentations.

In mice

Mice that are heterozygous for the agouti yellow allele have yellow coats and are more prone to obesity. Mice that are homozygous for the agouti yellow allele die during embryonic development because the yellow allele is a recessive lethal allele. Mice that are homozygous for the non-agouti alleles have non-agouti coat colors like black.

In mice, two mutations on Agouti are responsible for yellow coats and marked obesity, with other health defects.

In dogs

In dogs, the agouti gene is associated with various coat colors and patterns. [1] [2]

In cats

In cats, the dominant form of the agouti gene causes the tabby pattern, while the recessive form allows non-tabby coats.

In horses

In horses, Agouti restricts black pigment to specific areas of the body. Horses with the normal agouti gene have the genotype A/A or A/a. Horses without a normal agouti gene have the genotype a/a, and if they are capable of producing black pigment, it is uniformly distributed throughout the coat. A hypothesized third option, A^t, restricts black pigment to a black-and-tan pattern called seal brown. This allele is recessive to A and dominant to a, such that horses with the genotype A/A^t appear bay, while A^t/A^t and A^t/a horses are seal brown in the presence of a dominant Extension allele E.

The agouti gene, dominant over the black gene, limits or suppresses the black coloring to black points, allowing the underlying red coat color to come through. Unlike other types of "point" coloring, such as that seen in Siamese cats, the black points characteristic of bay coloring are not produced by a dilution or albinism gene.

The mode of inheritance of the Agouti gene is theorized to be complicated by the presence of more than 2 alleles. The theorized A^t allele appears to be responsible for Dark Brown to near black color colors that have lighter brown/tan color on the soft parts of the horse (muzzle, withers and around the eyes), such as this one.

The various shades of bay may be genetically produced by multiple factors, but a simple explanation of bay genetics is that "red" color, seen in the chestnut horse, represented by the recessive "e" allele; and black color, represented by the dominant "E" allele, are the two most basic coat color genes. All other colors are produced by the action of additional alleles acting on these two base colors.

In normal horses, ASIP restricts the production of eumelanin to the "points": the legs, mane, tail, ear edges, etc. In 2001, researchers discovered a recessive mutation on Asip that, when homozygous, left the horse without any ASIP. As a result, horses capable of producing true black pigment had uniformly black coats. One genetics testing lab began offering a test for A^t, but it was later found to be inaccurate and is no longer offered.

The black allele is caused by an 11 base pair deletion in exon 2 of ASIP.

Agouti phenotypes

• A/A wildtype, homozygous. Visually, the horse may be bay, buckskin, bay dun, amber champagne, and so on, or gray, or any member of the red family. However, such a horse will never be black, grullo, and so on, nor will a homozygous A horse ever produce uniform-black offspring or seal brown offspring.
• A/A^t Heterozygous Agouti. Visually Indistinguishable from the homozygous A Bay colored horse. Such horses are unable to produce Black colored foal.
• A/a wildtype, Heterozygous Agouti. Visually Indistinguishable from homozygous A. With the right partner, such horses have the ability to produce Black colored foals.
• A^t/A^t Theorized mutation of Agouti known as Brown or Seal Brown. In the absence of a dominant E allele. The presence of the theorized Agouti mutation A^t A Theorized mutation of the Agouti gene which is responsible in modifying the coat by restricting eumelanin in the coat to the points of the horse (Legs, ears, mane and tail). In the presence of at least 1 dominant E allele, the theorized mutation results in what is a [Brown/Seal Brown (horse)|brown] coat color. The Color is that of a Brown to almost black color body with light brown to tan hairs on the muzzle, around the eyes and on the withers of the horse. Variations of the theorized brown/seal brown coat color include: Dark Buckskin (also referred to as Smokey Brown) - A brown based horse with 1 cream gene; Perlino - a brown horse with 2 cream genes; Brown Dun - A brown based horse with at least 1 dun gene; and Sable Champagne - A brown based coat with at least 1 Champagne gene.
• A^t/a Indistinguishable from the homozygous Brown. Such horses have the ability to produce Black and black based colored horses.
• a/a homozygous recessive. Visually, in the presence of a dominant E allele, the horse's coat will be black. With the presence of a single cream gene, the coat will be smoky black, and with the presence of 2 cream genes the coat will be smoky cream. The Presence of at least 1 Dun gene will result in a grullo colored coat (Black Dun). The presence of at least 1 Champagne gene will result in classic champagne coat, and the presence of the at least 1 Silver gene will turn the black coat into a silver black coat, and so on.

History

The cause behind the various shades of bay, particularly the genetic factors responsible for wild bay and seal brown, have been contested for over 50 years. In 1951, zoologist Miguel Odriozola published "A los colores del caballo" in which he suggested four possible alleles for the "A" gene. He described an order of dominance between the alleles and the associated phenotypes:

• a, the least dominant, must be homozygous to be observed and is responsible for unrestricted black coat (non-agouti black),
• A^t, only visible in the homozygous form or when paired with a, is responsible for the black-and-tan seal brown coat,
• A, visible when homozygous or when paired with a or A^t, is responsible for the standard bay coat,
• A+, dominant, is responsible for the wildtype wild bay coat.

This was accepted until the 1990s, when a new theory became popular. The new theory suggested that shades of bay were caused by many different genes, some which lightened the coat, some which darkened it. This theory also suggested that seal brown horses were black horses with a trait called pangare. Pangaré is an ancestral trait also called "mealy", which outlines the soft or communicative parts of the horse in buff tan.

The pale areas on this bay horse are due to the pangaré trait

The combination of black and pangaré was dismissed as the cause of brown in 2001, when a French research team published Mutations in the agouti (ASIP), the extension (MC1R), and the brown (TYRP1) loci and their association to coat color phenotypes in horses (Equus caballus). This study used a DNA test to identify the recessive a allele on the Agouti locus, and found that none of the horses fitting the phenotype of seal brown were homozygous for the a allele.

Since 2001, the mechanisms of the variations within the "bay" category remain unclear. Ongoing research suggests that Odriozola's theories may have been correct, evidenced by a parallel condition in mice. Mice have more than six alleles at the Agouti locus, including A^t which produces black-and-tan.

It is still likely that to some extent, the "shade" of coat color may be regulated by unrelated genes for traits like "sooty", and that the phenotypes of sooty or dark bays/browns may overlap.

In rabbits

TODO

In hamsters

Not sure this section will be needed

In goats

[3]