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Dun gene

The Dun gene is a dominant at the TBX3 locus in that produces a distinctive color dilution effect, lightening the while leaving the primitive markings—such as a dorsal stripe along the spine, darker ear tips, face mask, and leg barring—unaffected, thereby creating a pattern ancestral to wild equids. This gene acts by regulating asymmetric pigmentation in hair follicles, inhibiting production in specific regions to generate the diluted shades (e.g., yellow dun on base, red dun on , or on black) without altering the primitive markings' dark pigmentation. Genetically, the Dun phenotype results from the functional D allele, which contrasts with two non-dun variants: nd1, which lacks dilution but may retain faint primitive markings, and nd2, a more recent mutation post-domestication that eliminates both dilution and markings entirely. The D allele is inherited in an autosomal dominant manner, meaning heterozygous (D/nd) and homozygous (D/D) horses exhibit identical dun coloration with no dosage effect, while non-dun horses (nd1/nd1, nd1/nd2, or nd2/nd2) display the typical undiluted base coat colors of modern domesticated breeds. The non-dun2 allele includes a 1,617-base-pair deletion in a regulatory region of the TBX3 gene, which impairs TBX3 expression and eliminates both coat dilution and primitive markings. The functional dun (D) allele allows normal TBX3 expression to regulate asymmetric pigmentation in hair follicles, inhibiting melanin production selectively in body hairs. The genetic basis of the Dun gene was elucidated in a 2016 study published in Nature Genetics, where researchers sequenced DNA from diverse breeds and ancient samples, confirming TBX3's role and tracing the alleles' origins to pre-domestication wild populations, including Przewalski's horses and even 43,000-year-old Pleistocene specimens. This discovery highlighted dun as the wild-type camouflage pattern in equids, with non-dun mutations arising later and becoming prevalent in many modern breeds due to for solid colors. is notably fixed or common in primitive breeds like the Norwegian Fjord (nearly 100% dun), , and , but rare in Thoroughbreds and absent in many Warmbloods, aiding breed identification and conservation efforts through .

Overview

Definition and Characteristics

The Dun gene refers to a dominant in the TBX3 , which encodes a T-box that regulates asymmetric pigmentation during hair follicle development in equines. This mutation disrupts radial symmetry in pigment deposition, leading to dilution of the body coat while sparing darker pigmentation in the head, , , and lower legs. Located on equine (ECA8), the gene's effect manifests as a dilution overlay on underlying base coat colors such as , , or . As an ancestral wild-type in equines, the Dun gene produces a characterized by a lightened body coat that enhances through , with the dilution typically resulting in sandy, tan, or yellowish tones depending on the base color. For instance, a classic dun exhibits a yellowish body coat contrasted by darker primitive markings, including a prominent stripe along the spine and transverse leg barring. These markings, remnants of ancestral patterning, are consistently present in Dun individuals. The term "dun" originates from dunn, describing a dull or dingy hue, which aptly captures the muted, earthy tones of the diluted . This has persisted in equine to denote the gene's influence across breeds and species.

Evolutionary and Historical Context

The gene was first identified in 2015 through a (GWAS) conducted by Imsland et al., which linked the to regulatory elements in the TBX3 gene on equine chromosome 8. This discovery revealed that results from the wild-type , while derived mutations in TBX3 regulatory regions cause the non- phenotype, characterized by more uniform pigmentation. Evolutionarily, the Dun allele represents the ancestral wild-type state in equids, as evidenced by its fixed presence in all extant wild species, including , , , and . This primitive coloration likely provided camouflage advantages in natural environments, with asymmetric pigment deposition creating patterns. evidence supports the prevalence of the Dun in predomestication horses. One non-Dun (non-dun1) predates , appearing in from a ~43,000-year-old Siberian horse, while the other (non-dun2) emerged more recently. Following horse domestication around 5,500 years ago on the , favored solid, non- coat colors for aesthetic or cultural reasons, leading to the rapid spread of non-dun2 mutations during the early (~5,000–6,000 years ago). This shift reduced Dun prevalence in domestic but preserved it in conserved . Recent research by Cieslak et al. in 2021 analyzed the Polish (Konik), a bred to resemble the extinct , and found a of 84% in a sampled , underscoring its retention in populations maintained for historical authenticity.

Taxonomic Distribution

Presence in Wild Equids

The Dun allele is nearly ubiquitous in wild equids, serving as the ancestral wild-type coloration across various species. In (Equus ferus przewalskii), the last surviving wild horse subspecies, individuals are homozygous for the Dun allele (D/D), resulting in a characteristic dun coat with primitive markings such as a dorsal stripe and leg barring. Similarly, other wild equids including the (Equus hemionus), (Equus kiang), (Equus africanus), and extinct (Equus quagga quagga) and (Equus ferus ferus) exhibit homozygous Dun genotypes, as evidenced by the presence of key regulatory SNPs in the TBX3 gene that define the D allele. Zebras ( spp.) carry the Dun allele, and it has been hypothesized that their stripes represent an extension of the primitive markings associated with the Dun phenotype. Genetic analyses confirm that all examined modern wild equids are homozygous for the dominant Dun allele (D/D), with no instances of non-dun genotypes observed, underscoring the allele's fixation in natural populations. This distribution contrasts with domestic horses, where non-dun variants predominate, and highlights Dun as the default state in undomesticated equids. The ancestral status of Dun, briefly referenced in evolutionary studies, aligns with its consistent expression of primitive markings in these species. The Dun phenotype provides adaptive camouflage benefits in the arid and steppe habitats of wild equids, where the diluted body coat blends with sandy or dusty environments, while undiluted dark stripes and mane offer disruptive patterning against predators. This coloration likely contributed to survival in open landscapes, as the reduced pigment intensity minimizes visibility during daylight foraging. Conservation efforts for endangered wild equids, particularly Przewalski's horses, inherently preserve the Dun allele, as reintroduction programs maintain homozygous D/D populations to sustain genetic integrity and wild-type traits. With Przewalski's horses numbering approximately 2,000–2,500 individuals globally as of , including captive and rewilded groups, ongoing breeding management ensures the retention of this ancestral coloration amid habitat restoration in and .

Prevalence in Domestic Species

The prevalence of the Dun allele varies significantly across domestic horse breeds, reflecting historical breeding practices that favored or selected against the dilution effect in different populations. In primitive or landrace breeds, the Dun allele remains at high frequencies due to less intensive selection for uniform coat colors. For instance, a study of the Vyatka breed in found that 35.5% of genotyped individuals were homozygous for Dun (DD), 61.3% were heterozygous (Dd), and only 3.2% carried the recessive non-dun allele (nd2/nd2), indicating a strong persistence of the trait in this ancient breed. Similarly, the approaches fixation in certain breeds maintained for traditional phenotypes. Regional and breed-specific variations highlight the influence of geographic isolation and cultural preferences on Dun prevalence. Norwegian Fjord horses are nearly fixed for the Dun allele, with all registered individuals exhibiting the dun phenotype, a result of breed standards that preserve the ancestral coloration. In Icelandic horses, the Dun allele is rare, with no detections in recent breed surveys of over 60 individuals, though individual heterozygotes have been noted in earlier genetic studies. Conversely, modern performance breeds show low Dun frequencies due to against dilution for aesthetic or competitive reasons; for example, the allele is rare in Warmbloods, where non-dun coats predominate, and it is infrequently observed in Thoroughbreds, where historical selection has favored solid colors. The advent of commercial genetic testing has profoundly impacted the detection and management of Dun alleles in domestic horses. Tests such as the Dun zygosity panel from the University of California, Davis Veterinary Genetics Laboratory distinguish between dominant Dun (D), non-dun1 (nd1), and non-dun2 (nd2) variants, enabling identification of heterozygous carriers that do not express visible dilution. This has led to increased awareness of hidden Dun carriers in breeds with low apparent prevalence, facilitating targeted breeding programs to restore genetic diversity and reintroduce the allele in populations where it had been diminished. While the primary focus remains on equines, rare Dun-like dilution effects have been noted in domestic donkeys, where a TBX3 gene mutation similarly influences primitive markings and body lightening, though these are less studied and not as variably selected as in horses.

Phenotypic Effects

Coat Color Dilution

The Dun gene causes a dilution of the base coat color in equines by reducing melanin production in the hair shaft, resulting in a lighter overall appearance of the body coat while preserving darker pigmentation in primitive areas such as the mane, tail, legs, and ears. This dilution typically lightens the body hair by one to two shades, transforming bay to a tan or golden hue (bay dun), black to a smoky gray or mouse-colored tone (grullo or blue dun), and chestnut to a light tan or pale red (red dun or sorrel dun). The effect arises from radially asymmetric deposition of pigment, limiting melanin to approximately 25–50% of the hair cortex in affected areas, which creates the characteristic washed-out look compared to non-dun counterparts. Both heterozygous (D/nd) and homozygous (D/D) Dun genotypes produce equivalent dilution levels, with no discernible difference in coat lightness or pattern intensity between them, and unlike certain other dilution genes such as cream in double dose, the Dun gene carries no lethal effects. The Dun dilution acts as an overlay on the underlying base coat colors determined by the Extension and loci, without fundamentally altering their distribution—for instance, it does not convert black pigment to red, maintaining the distinction between dun (with black points) and red dun (with red points). This overlay preserves the integrity of the base color while imparting a uniform fading to the body, aiding in visual identification of horses through their notably paler, sun-bleached appearance relative to solid-colored individuals of the same base. The mechanism involves regulatory mutations in the TBX3 gene, which disrupt symmetric pigmentation in hair follicles.

Primitive Markings and Variants

The primitive markings associated with the Dun gene are distinctive dark, undiluted features that contrast against the diluted body coat, serving as to enhance in a manner reminiscent of wild equids. These include a prominent stripe extending from the to the , often referred to as the "eel stripe," which runs along the spine and provides a dark midline that blends the animal into varied terrains. Horizontal leg barring appears as zebra-like stripes across the legs, particularly noticeable on the forelegs, while shoulder stripes form cross-like patterns over the and shoulder blades. Additionally, a darkens the muzzle and eye areas, sometimes accompanied by cobwebbing or concentric rings around the eyes, creating an overall pattern that disrupts the outline for predatory evasion. In horses carrying the Dun allele (D), these markings are bold and fully expressed regardless of whether the genotype is heterozygous (D/nd1 or D/nd2) or homozygous (D/D), contributing to a striking wild-type appearance. Variant expressions can occur in the absence of the Dun dilution, where the non-dun1 allele (nd1/nd1) produces faint primitive markings, such as subtle leg barring, without significant body lightening, while non-dun2 (nd2/nd2) typically eliminates them entirely. Breed-specific consistency is evident in the Norwegian Fjord horse, which is nearly fixed for the homozygous Dun genotype, resulting in vivid eel stripes, dark midsections in the and (known as "midstol" and "halefjaer"), and pronounced and barring that accentuate its , robust silhouette. These markings visually emphasize the Dun phenotype's evolutionary ties to ancestral camouflage, where the dark stripes and masks break up the lighter body coat to mimic dappled light and shadow in natural habitats, as observed in diagrammatic representations of dun equids showing enhanced outline disruption compared to non-dun counterparts.

Genetic Mechanisms

Molecular Basis

The Dun phenotype in horses arises from the action of the TBX3 gene, which encodes a T-box critical for regulating development and differentiation. In the ancestral Dun allele, TBX3 promotes radially asymmetric distribution within individual hair shafts by influencing the positioning and activity of melanocytes during follicle growth. Genome-wide association studies (GWAS) and targeted sequencing identified the causal regulatory variants distinguishing from non-Dun alleles in a conserved enhancer element approximately 5 kb downstream of TBX3 on equine chromosome 8. Specifically, non-Dun1 features a (SNP) at position chr8:18,227,267 (G in Dun, T in non-Dun1), which disrupts binding sites for CCAT box transcription factors such as NF-Y and NF-I, while non-Dun2 involves a 1,617 bp deletion at chr8:18,227,267–18,228,883, eliminating binding motifs for ALX4 and MSX2. These mutations reduce TBX3 transcriptional activity specifically in follicles, leading to symmetric production and loss of dilution, whereas primitive marking regions retain enhancer function and asymmetric expression. Contrary to earlier hypotheses, no retroviral insertion characterizes the allele itself; instead, it represents the functional ancestral state. At the cellular level, TBX3 in Dun follicles is expressed asymmetrically along the dermal-epidermal boundary, suppressing KIT ligand (KITLG) expression on the ventral side of the hair, which restricts and synthesis to the dorsal , resulting in localized dilution. This mechanism spares primitive markings, where symmetric TBX3 expression maintains full pigmentation. Expression analyses in dun Mongolian Bider horses confirm region-specific TBX3 regulation, with quantitative real-time revealing significantly higher TBX3 mRNA levels in dark-colored regions such as the and Bider markings compared to light-colored body regions, alongside elevated protein abundance via in pigmented areas. These differences directly correlate with observed pigmentation patterns, underscoring TBX3's role in spatially controlled dilution.

Alleles and Inheritance Patterns

The Dun gene at the TBX3 locus exhibits three primary alleles: the dominant Dun allele (D), which produces the characteristic dilution and primitive markings; the recessive non-dun1 allele (nd1), associated with partial or variable primitive markings in homozygous individuals; and the recessive non-dun2 allele (nd2), which lacks such markings. The nd1 allele is ancient, predating horse domestication and present in wild equid populations for over 40,000 years, while nd2 arose more recently, after approximately 4,000 BCE, coinciding with early domestication processes. Genotypes at this locus follow simple with complete dominance of D over both nd1 and nd2. Horses homozygous for the allele (D/D) display the phenotype, as do heterozygotes (D/nd1 or D/nd2); in contrast, non-dun phenotypes occur in homozygotes for either recessive (nd1/nd1, nd2/nd2) or compound heterozygotes (nd1/nd2), with no dilution effect. There is no phenotypic dosage difference between D/D and D/nd genotypes, both expressing equivalent traits. Inheritance operates via autosomal dominance, enabling predictable outcomes. For instance, mating a heterozygous horse (D/nd) with a homozygous non-dun horse (nd/nd) results in 50% offspring (D/nd) and 50% non-dun offspring (nd/nd), as shown in this :
Dnd
ndD/nd ()nd/nd (non-dun)
ndD/nd ()nd/nd (non-dun)
This 1:1 ratio holds regardless of whether nd represents nd1 or nd2. Zygosity testing identifies these alleles through targeted assays, including detection of single nucleotide polymorphisms (SNPs) at specific positions in TBX3 (such as chr8:18,227,267 and chr8:18,226,905) and a 1,617 bp deletion diagnostic for nd2 via amplification and sequencing. Such tests, offered by veterinary genetics laboratories, confirm status and distinguish nd1 from nd2 in non-dun horses, aiding .

Dun-Like Mimics

Several equine coat colors superficially resemble the phenotype through partial dilution or patterns but lack the characteristic genetic basis and full suite of primitive markings associated with the Dun gene at the TBX3 locus. These mimics arise from distinct loci, such as SLC45A2 for cream dilution or PMEL for silver dilution, leading to potential confusion in visual identification without . Buckskin, resulting from a single copy of the cream dilution gene (CR) on a bay base, produces a golden-tan body with black points and legs, often exhibiting subtle along the dorsal midline that can mimic a faint stripe. Unlike true , buckskin lacks distinct primitive markings such as leg barring or shoulder stripes, and the dilution primarily affects red pigment while leaving black unchanged. Perlino, a double cream dilution (CR/CR) on a bay base, yields a pale coat with slightly darker red points, pink skin, and blue eyes, creating an overall washed-out appearance that may superficially echo Dun's lightening effect but without any striping or barring. This is distinguished by its uniform paleness and absence of countershading patterns typical of Dun. Roan patterns, caused by variants in the KIT gene, intermix white hairs throughout the body coat while preserving solid coloration on the head, mane, tail, and lower legs, sometimes producing irregular striping or mottling that resembles Dun's primitive markings in certain lighting or patterns like sabino-roan overlays. However, roan does not dilute the base pigment and instead scatters white hairs progressively, lacking the even body lightening and defined dorsal stripe of Dun. Silver dapple, due to a mutation in PMEL, dilutes black pigment on bay or black bases to a chocolate-brown body with flaxen or silver-gray mane and tail, often displaying dappled spots that can mimic the mousy grullo (Dun on black) shade. This effect is limited to eumelanin (black pigment) and does not alter red areas, differing from Dun's balanced dilution of both pigments and presence of authentic primitive markings. A notable genetic mimic is the Non-Dun1 (nd1) variant at the TBX3 locus, which produces primitive markings like dorsal stripes and leg barring without the accompanying coat dilution seen in functional Dun alleles. Horses homozygous for nd1 (nd1/nd1) exhibit these countershading features on non-diluted coats, leading to frequent misclassification as Dun, particularly in breeds like Icelandic or Canadian horses where the variant is prevalent. This regulatory mutation disrupts asymmetric pigmentation but fails to achieve the full Dun dilution, allowing differentiation via targeted sequencing. Differentiation of these mimics from true Dun relies on genetic testing to confirm the presence of functional TBX3 variants versus mutations at other loci, such as MC1R (for red factor assessment in cream interactions) or KIT for roan. Visually, mimics often lack the crisp, even primitive markings of Dun, showing instead inconsistent countershading, dappling, or progressive whitening; for instance, buckskins may have a shadowy dorsal line but no transverse leg stripes.
Mimic ColorGenetic BasisBody ShadeMane/Tail ColorMarkingsKey Difference from Dun
BuckskinSingle cream (SLC45A2) on bayGolden-tanBlackSubtle countershading, no barringNo dilution of black points; lacks defined stripes
PerlinoDouble cream (SLC45A2) on bayPale creamReddish-creamNone or faint countershadingUniform paleness without primitive patterns
RoanKIT variants on any baseIntermixed white/coloredSolid base colorIrregular mottling, possible false stripingNo pigment dilution; white hairs increase with age
Silver DapplePMEL on black/bayChocolate-brownFlaxen/silver-grayDapples, occasional countershadingAffects only black pigment; no red dilution or true barring
Non-Dun1TBX3 nd1 variantNon-diluted baseBase colorPrimitive markings without dilutionMarkings present but body color undiluted

Interactions with Other Color Genes

The Dun gene interacts with other equine coat color loci to produce compound phenotypes, primarily through additive dilution effects on base colors determined by the extension (MC1R) and agouti (ASIP) loci. Dun dilutes both eumelanin (black pigment) and phaeomelanin (red pigment) produced by these loci, resulting in lighter body coats while preserving primitive markings on diluted backgrounds such as bay dun, red dun, or grulla (black dun). A prominent interaction occurs with the cream dilution gene (SLC45A2), where a single copy of cream on a chestnut base combined with yields dunalino, characterized by a golden body with primitive markings and undiluted points. Double cream dilution (homozygous Cr/Cr) with further lightens the coat; for instance, on a black base (E/-; a/a; D/-; Cr/Cr), it produces a smoky cream-like phenotype but retains 's dark dorsal stripe, leg barring, and other primitive markings, distinguishing it from non- smoky cream. Dun also combines with the silver dilution (PMEL, Z locus), which primarily affects black pigment. In silver dun grullo horses (E/-; a/a; D/-; Z/-), the silver gene causes additional fading of the mane and tail to a flaxen or chocolate tone atop the grulla's mouse-gray body, enhancing the dilution without altering Dun's primitive markings. Regarding roan (KIT locus), Dun exerts partial epistatic override by diluting the base color into which white hairs are interspersed, while keeping primitive markings largely unroaned and dark. This results in a roan dun phenotype where the body shows mixed diluted and white hairs, but points and stripes remain prominently colored. In contrast, shows no epistatic interaction with the leopard complex (TRPM1, locus); the two simply overlay, with diluting the pigmented areas amid leopard spotting patterns, as seen in dun Appaloosas. A 2024 review of multi-locus interactions in equine coat colors highlights these combinations, emphasizing their role in breed-specific phenotypes and breeding predictions via .

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