Science 封面文章：破譯犬類體型大小關鍵基因

美國康奈爾大學等單位的研究人員，最近鑑別出決定狗體型大小的關鍵基因IGF1，向弄清人類體型大小差異邁出重要一步。相關文章被選為4月6日《Science》封面文章。

研究人員通過在骨骼尺寸變化較大的葡萄牙水犬（Portuguese water dogs）中對比個體DNA差異，發現小體型和大體型個體有差異的基因組區域。其中一個區域包括編碼胰島素樣生長因子1（insulin-like growth factor 1，IGF1）基因，於是研究人員在開始包括奇瓦瓦犬（Chihuahuas）、玩具更犬（Toy Fox Terrier）和博美犬( Pomeranian)在內的14種小體型狗和包括獵狼犬（Irish wolfhounds）、聖伯納犬(Saint Bernard)和大丹犬(Great Dane)在內的9種大體型狗中分析此區域。

奇怪的是，大多數小體型狗擁有一段與大體型葡萄牙水犬相似的DNA片段，但大體積葡萄牙水犬、狼犬和豺狗等野生犬中沒有這段DNA。研究人員推測，在狗馴化歷史早期出現的一個基因突變，產生了「小狗」版的IGF1， 並隨著馴化過程逐漸在小體型狗中固定下來，提示IGF1在決定同一品種狗體型大小差異中的作用，與在小體型狗品種與大體型狗品種分離過程中的作用相似。

「這麼多種小體積狗品種是由對同一個基因的同一種突變的選擇實現的，令人驚愕。這些結果提示儘管不同品系間存在各種各樣的差異（甚至基因大小），IGF1作為一個一貫影響體型大小的基因，在眾多小體積品種狗的進化過程種發揮重要作用，」 Bustamante說，研究證明了家狗模式系統對鑑定重要基因（研究）中的作用。

因為小體型狗品種相互間親緣關係較遠，研究人員認為小體型狗間的基因變異在進化歷史中出現較早，通過若干代的人工選育，現代狗已經成為個體間體型差異最大的哺乳動物。



Science 6 April 2007:
Vol. 316. no. 5821, pp. 112 - 115
DOI: 10.1126/science.1137045


Reports
A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs
Nathan B. Sutter,1 Carlos D. Bustamante,2 Kevin Chase,3 Melissa M. Gray,4 Keyan Zhao,5 Lan Zhu,2 Badri Padhukasahasram,2 Eric Karlins,1 Sean Davis,1 Paul G. Jones,6 Pascale Quignon,1 Gary S. Johnson,7 Heidi G. Parker,1 Neale Fretwell,6 Dana S. Mosher,1 Dennis F. Lawler,8 Ebenezer Satyaraj,8 Magnus Nordborg,5 K. Gordon Lark,3 Robert K. Wayne,4 Elaine A. Ostrander1*

The domestic dog exhibits greater diversity in body size than any other terrestrial vertebrate. We used a strategy that exploits the breed structure of dogs to investigate the genetic basis of size. First, through a genome-wide scan, we identified a major quantitative trait locus (QTL) on chromosome 15 influencing size variation within a single breed. Second, we examined genetic variation in the 15-megabase interval surrounding the QTL in small and giant breeds and found marked evidence for a selective sweep spanning a single gene (IGF1), encoding insulin-like growth factor 1. A single IGF1 single-nucleotide polymorphism haplotype is common to all small breeds and nearly absent from giant breeds, suggesting that the same causal sequence variant is a major contributor to body size in all small dogs.

1 National Human Genome Research Institute, Building 50, Room 5349, 50 South Drive MSC 8000, Bethesda, MD 20892–8000, USA.
2 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14850, USA.
3 Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
4 Department of Ecology and Environmental Biology, University of California, Los Angeles, CA 90095, USA.
5 Department of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
6 The WALTHAM Centre for Pet Nutrition, Waltham on the Wolds, Leicestershire, LE14 4RT, UK.
7 Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
8 Nestle Research Center (NRC-STL), St. Louis, MO 63164, USA.