Dominant Red Coat Color in Holstein Cattle Is Associated with a Missense Mutation in the Coatomer Protein Complex, Subunit Alpha (COPA) Gene.
Dominant Red Coat Color in Holstein Cattle Is Associated with a Missense Mutation in the Coatomer Protein Complex, Subunit Alpha (COPA) Gene.
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DOI：
10.1371/journal.pone.0128969
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Andersson L
中科院分区：
文献类型：
--
作者：
Dorshorst B;Henegar C;Liao X;Sällman Almén M;Rubin CJ;Ito S;Wakamatsu K;Stothard P;Van Doormaal B;Plastow G;Barsh GS;Andersson L
荷斯坦奶牛的毛色主要由黑皮质素1受体（MC 1 R）基因控制，MC 1 R基因是跨动物物种的黑色（真黑素）与红色/棕色褐黑素合成的中心决定因素。荷斯坦牛的MC 1 R等位基因主要是显性黑（MC 1 RD）和隐性红（MC 1 Re）。1980年，在一只出生的动物身上首次观察到一种新的显性红色毛色。这种表型的突变被命名为显性红，是上位的组成型激活MC 1 RD。在这里，我们表明，错义突变的外套蛋白复合物，亚基α（COPA），一个基因，以前没有已知的色素合成的作用，是完全与显性红荷斯坦奶牛。该突变导致在真核生物中完全保守的氨基酸残基处精氨酸被半胱氨酸取代。尽管这种高水平的保守性，我们表明，无论是杂合子和纯合子是健康和可行的。对毛发色素组成的分析表明，显性红表型与MC 1 R隐性红表型相似，尽管在减少真黑素合成方面效果较差。RNA-seq数据类似地显示，显性红动物通过下调真黑素合成通常所需的基因来实现主要的褐黑素合成。COPA是外壳蛋白I七亚基复合物的组分，其参与蛋白质和RNA货物的逆行和顺式高尔基体细胞内包被囊泡转运。这表明显性红可能是由高度区室化的黑素细胞内异常的MC 1 R蛋白或mRNA运输引起的，模拟了隐性红功能丧失MC 1 R等位基因的作用。
Coat color in Holstein dairy cattle is primarily controlled by the melanocortin 1 receptor (MC1R) gene, a central determinant of black (eumelanin) vs. red/brown pheomelanin synthesis across animal species. The major MC1R alleles in Holsteins are Dominant Black (MC1RD) and Recessive Red (MC1Re). A novel form of dominant red coat color was first observed in an animal born in 1980. The mutation underlying this phenotype was named Dominant Red and is epistatic to the constitutively activated MC1RD. Here we show that a missense mutation in the coatomer protein complex, subunit alpha (COPA), a gene with previously no known role in pigmentation synthesis, is completely associated with Dominant Red in Holstein dairy cattle. The mutation results in an arginine to cysteine substitution at an amino acid residue completely conserved across eukaryotes. Despite this high level of conservation we show that both heterozygotes and homozygotes are healthy and viable. Analysis of hair pigment composition shows that the Dominant Red phenotype is similar to the MC1R Recessive Red phenotype, although less effective at reducing eumelanin synthesis. RNA-seq data similarly show that Dominant Red animals achieve predominantly pheomelanin synthesis by downregulating genes normally required for eumelanin synthesis. COPA is a component of the coat protein I seven subunit complex that is involved with retrograde and cis-Golgi intracellular coated vesicle transport of both protein and RNA cargo. This suggests that Dominant Red may be caused by aberrant MC1R protein or mRNA trafficking within the highly compartmentalized melanocyte, mimicking the effect of the Recessive Red loss of function MC1R allele.
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影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
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影响因子：
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DOI：
10.1073/pnas.0703805104
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