Significance of the Evolutionary α1,3-Galactosyltransferase (GGTA1) Gene Inactivation in Preventing Extinction of Apes and Old World Monkeys

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• 作者：Uri Galili
• 关键词：α1 ; 3 ; Galactosyltransferase ; Primate evolution ; α ; Gal epitope ; Primate extinction ; Anti ; Gal antibody ; GGTA1
• 刊名：Journal of Molecular Evolution
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：80
• 期：1
• 页码：1-9
• 全文大小：372 KB
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  20. Daw
• 作者单位：Uri Galili (1) (2)
  
  1. UMass Medical School, Worcester, MA, USA
  2. 910 South Michigan Avenue, Apt. 1404, Chicago, IL, 60605, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Microbiology
  Plant Sciences
  
• 出版者：Springer New York
• ISSN：1432-1432

文摘

The α1,3-galactosyltransferase (α1,3GT or GGTA1) gene displays unique evolutionary characteristics. This gene appeared early in mammalian evolution and is absent in other vertebrates. The α1,3GT gene is active in marsupials, nonprimate placental mammals, lemurs (prosimians) and New World monkeys, encoding the α1,3GT enzyme that synthesizes a carbohydrate antigen called “οgal epitope.-The α-gal epitope is present in large numbers on cell membrane glycolipids and glycoproteins. The α1,3GT gene was inactivated in ancestral Old World monkeys and apes by frameshift single-base deletions forming premature stop codons. Because of this gene inactivation, humans, apes, and Old World monkeys lack α-gal epitopes and naturally produce an antibody called the “anti-Gal antibody-which binds specifically to α-gal epitopes and which is the most abundant antibody in humans. The evolutionary event that resulted in the inactivation of the α1,3GT gene in ancestral Old World primates could have been mediated by a pathogen endemic to Eurasia–Africa landmass that exerted pressure for selection of primate populations lacking the α-gal epitope. Once the α-gal epitope was eliminated, primates could produce the anti-Gal antibody, possibly as means of defense against pathogens expressing this epitope. This assumption is supported by the fossil record demonstrating an almost complete extinction of apes in the late Miocene and failure of Old World monkeys to radiate into multiple species before that period. A present outcome of this evolutionary event is the anti-Gal-mediated rejection of mammalian xenografts expressing α-gal epitopes in humans, apes, and Old World monkeys.