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Molecular basis of evolutionary loss of the α1,3-galactosyltransferase gene in higher primates

Koike, C and Fung, JJ and Geller, DA and Kannagi, R and Libert, T and Luppi, P and Nakashima, I and Profozich, J and Rudert, W and Sharma, SB and Starzl, TE and Trucco, M (2002) Molecular basis of evolutionary loss of the α1,3-galactosyltransferase gene in higher primates. Journal of Biological Chemistry, 277 (12). 10114 - 10120. ISSN 0021-9258

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Abstract

Galactose-α1,3-galactose (αGal) epitopes, the synthesis of which requires the enzyme product of α1,3-galactosyltransferase (α1,3GT), are sugar chains on the cell surface of most mammalian species. Notable exceptions are higher primates including Old World monkeys, apes, and humans. The αGal-negative species as well as mice with deletion of the α1,3GT gene produce abundant anti-αGal antibodies. The evolutionary loss of αGal epitopes has been attributed to point mutations in the coding region of the gene. Because no transcripts could be found in the higher primate species with Northern blot analysis, a potential alternative explanation has been loss of upstream regulation of the gene. Here, we have demonstrated that the rhesus promoter is functional. More importantly, a variety of full-length transcripts were detected with sensitive PCR-based methods in the tissues of rhesus monkeys, orangutans, and humans. Five crucial mutations were delineated in the coding region of the human and rhesus and three in the orangutan, any one of which could be responsible for inactivation of the α1,3GT gene. Two of the mutations were shared by all three higher primates. These findings, which elucidate the molecular basis for the evolutionary loss of αGal expression, may have implications in medical research.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Koike, C
Fung, JJ
Geller, DAdageller@pitt.eduDAGELLER
Kannagi, R
Libert, T
Luppi, P
Nakashima, I
Profozich, J
Rudert, W
Sharma, SB
Starzl, TEtes11@pitt.eduTES11
Trucco, M
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 22 March 2002
Date Type: Publication
Journal or Publication Title: Journal of Biological Chemistry
Volume: 277
Number: 12
Page Range: 10114 - 10120
DOI or Unique Handle: 10.1074/jbc.m110527200
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0021-9258
Other ID: uls-drl:31735062120799, Starzl CV No. 2169
Date Deposited: 08 Apr 2010 17:37
Last Modified: 13 Oct 2017 22:59
URI: http://d-scholarship.pitt.edu/id/eprint/5555

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