基因研究人員發(fā)現(xiàn)，一個控制狗毛色的基因出乎意料地編碼一個屬于過去只知道是與抵抗微生物有關(guān)的蛋白質(zhì)家族的蛋白質(zhì)。在大多數(shù)哺乳動物中，毛色由兩個基因決定,，一個是負責深色的黑皮素受體-1(Melanocortin 1 receptor)基因，另一個是負責淺色的鼠灰色(Agouti)基因。但是在狗身上,，毛色還涉及到第三個基因。Sophie Candille和同事把該基因確定在狗DNA上被稱為K位點的一個小區(qū)域內(nèi),，該基因能解釋大多數(shù)品種狗的黃,、黑、或斑紋顏色的不同,，隨后的生物化學和小鼠實驗也支持這個結(jié)果,。這個與毛色有關(guān)的基因編碼CDB103，該蛋白質(zhì)是防御素(beta-defensin)的一個成員,，防御素是一類涉及內(nèi)在免疫的小蛋白質(zhì)家族,。防御素的這個超出免疫功能的新作用將引導研究人員發(fā)現(xiàn)防御素涉及的其它新功能。
原始出處:
Published Online October 18, 2007
Science DOI: 10.1126/science.1147880
Research Articles
Submitted on July 16, 2007
Accepted on October 3, 2007
A -Defensin Mutation Causes Black Coat Color in Domestic Dogs
Sophie I. Candille 1, Christopher B. Kaelin 1, Bruce M. Cattanach 2, Bin Yu 3, Darren A. Thompson 3, Matthew A. Nix 3, Julie A. Kerns 4, Sheila M. Schmutz 5, Glenn L. Millhauser 3, Gregory S. Barsh 1*
1 Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA.
2 MRC Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 ORD, UK.
3 Departments of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
4 Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA; Present address: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
5 Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Canada.
* To whom correspondence should be addressed.
Gregory S. Barsh , E-mail: [email protected]
These authors contributed equally to this work.
Genetic analysis of mammalian color variation has provided fundamental insight into human biology and disease. In most vertebrates, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls pigment type-switching, but in domestic dogs, a third gene is implicated, the K locus, whose genetic characteristics predict a new component of the melanocortin pathway. Here we identify the K locus as -defensin 103 (CBD103) and show that its protein product binds with high affinity to the Mc1r, and has a simple and strong effect on pigment type-switching in domestic dogs and transgenic mice. These results expand the functional role of -defensins, a protein family previously implicated in innate immunity, and identify an additional class of ligands for signaling through melanocortin receptors.
