Agouti coloration genetics


The agouti gene is responsible for variations in color in many species. Agouti works with extension to regulate the color of melanin which is produced in hairs. The agouti protein causes red to yellow pheomelanin to be produced, while the competing molecule α-MSH signals production of brown to black eumelanin. In wildtype mice, alternating cycles of agouti and α-MSH production cause agouti coloration. Each hair has bands of yellow which grew during agouti production, and black which grew during α-MSH production. Wildtype mice also have light-colored bellies. The hairs there are a creamy color the whole length because the agouti protein was produced the whole time the hairs were growing.
In mice and other species, loss of function mutations generally cause a darker color, while gain of function mutations cause a yellower coat.

Mice

As of 1979, there were 17 known alleles of agouti in mice.
This is not a complete list of mouse agouti alleles.
Lethal yellow and viable yellow cause obesity, features of type II diabetes, and a higher likelihood of tumors. In normal mice Agouti is only expressed in the skin during hair growth, but these dominant yellow mutations cause it to be expressed in other tissues including liver, muscle, and fat.
The mouse agouti gene is found on chromosome 2.

Dogs

In dogs, the agouti gene is associated with various coat colors and patterns.
The alleles at the A locus are related to the production of agouti-signaling protein and determine whether an animal expresses an agouti appearance and, by controlling the distribution of pigment in individual hairs, what type of agouti. There are four known alleles that occur at the A locus:
Most texts suggest that the dominance hierarchy for the A locus alleles appears to be as follows: Ay > aw > at > a; however, research suggests the existence of pairwise dominance/recessiveness relationships in different families and not the existence of a single hierarchy in one family.
The dominant, wild-type A allows hairs to be banded with black and red, while the recessive non-agouti or "hypermelanistic" allele, a, causes black pigment production throughout the growth cycle of the hair. Thus, the non-agouti genotype masks or hides the tabby pattern, although sometimes a suggestion of the underlying pattern can be seen, especially in kittens. The sex-linked orange coloration is epistatic over agouti, and prevents the production of black pigment.
AlleleSymbolImageDescriptionMutation
AgoutiATabby pattern thanks to a functional agouti gene.Wildtype
NonagoutiaBlack, which lacks a functional agouti gene and so cannot signal MC1R to produce red pigment.A 2 base pair frameshift deletion thought to cause a complete loss of function

Horses

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 functional ASIP. As a result, horses capable of producing true black pigment had uniformly black coats. The dominant, wildtype allele producing bay is symbolized as A, while the recessive allele producing black is symbolized as a. Extension is epistatic over agouti and will cause chestnut coloration regardless of what agouti alleles are present.
A hypothesized third option, At, might restrict black pigment to a black-and-tan pattern called seal brown. This allele would be recessive to A and dominant to a, such that horses with the genotype A/At appear bay, while At/At and At/a horses are seal brown in the presence of a dominant Extension allele E. One genetics testing lab began offering a test for At, but it was later found to be inaccurate and is no longer offered.
AlleleSymbolImageDescriptionMutation
Wild bayA+Wild bay pattern, like bay but the black does not extend so far up the legsHypothesized
BayABay pattern due to a functional agouti gene. The body is red while the "points", the mane, tail, and lower legs, are black.Wildtype
Seal brownatSeal brown color, mostly black but with some red on the flanks, muzzle, and around the eyesHypothesized
Nonagouti blackaBlack horses produce black pigment in the entire coat because they lack a functional Agouti protein.An 11 base pair frameshift deletion in exon 2

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, A+, A, At, and a, in order of most dominant to least.
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 combination of black and pangaré was dismissed as the cause of brown in 2001, when a French research team published Mutations in the agouti, the extension, and the brown loci and their association to coat color phenotypes in horses . 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 several alleles at the Agouti locus, including At which produces black-and-tan.

Donkeys

Most donkeys have creamy to gray-white areas on the belly and around the muzzle and eyes, called light points or pangare. However, a recessive variant of agouti causes those areas to be the same color as the body in a pattern called no light points or NLP, which is similar to recessive black in other mammals. This allele can be found in Norman donkeys and American miniature donkeys.
AlleleSymbolImageDescriptionMutation
Light pointsAA gray dun donkey with a white belly and white around the muzzleWildtype
No light pointsanlpA gray dun donkey with no white areasA single nucleotide polymorphism predicted to be deleterious to protein function

Rabbits

In rabbits, the wildtype is agouti with a light belly, and a recessive non-agouti allele causes a black coat. A third allele, possibly a mutation to a regulator or promoter region, is thought to cause black and tan color. The nonagouti allele is estimated to have first appeared before 1700.
Agouti is linked to the wideband gene, with about a 30% crossover rate.
Like white bellied agouti mice, rabbits with wildtype agouti produce transcripts with different untranslated 5' ends that have different dorsal and ventral expression. The 1A exon is only expressed in the belly region and may be responsible for the lighter color there.
AlleleSymbolImageDescriptionMutation
AgoutiAChestnut, sometimes called agouti. Hairs are banded black and yellow, and the belly is light. This resembles the mouse's light bellied agouti.Wildtype
Black and tanatBlack otter, black with a white belly. Tan rabbits are all this color, but also have the wideband pattern and rufous color causing their bellies to be fiery orange.Thought to exist from classical genetics studies, but not found molecularly. May be on a promoter or regulator of agouti.
NonagoutiaBlack self. All hairs are fully black.Single base pair frameshift insertion in exon 2 causing loss of function