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Molecular basis of evolutionary loss of the alpha 1,3-galactosyltransferase gene in higher primates.


ABSTRACT: Galactose-alpha1,3-galactose (alphaGal) epitopes, the synthesis of which requires the enzyme product of alpha1,3-galactosyltransferase (alpha1,3GT), are sugar chains on the cell surface of most mammalian species. Notable exceptions are higher primates including Old World monkeys, apes, and humans. The alphaGal-negative species as well as mice with deletion of the alpha1,3GT gene produce abundant anti-alphaGal antibodies. The evolutionary loss of alphaGal 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 alpha1,3GT gene. Two of the mutations were shared by all three higher primates. These findings, which elucidate the molecular basis for the evolutionary loss of alphaGal expression, may have implications in medical research.

SUBMITTER: Koike C 

PROVIDER: S-EPMC3018882 | biostudies-literature | 2002 Mar

REPOSITORIES: biostudies-literature

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Molecular basis of evolutionary loss of the alpha 1,3-galactosyltransferase gene in higher primates.

Koike Chihiro C   Fung John J JJ   Geller David A DA   Kannagi Reiji R   Libert Therese T   Luppi Patrizia P   Nakashima Izumi I   Profozich Jennifer J   Rudert William W   Sharma Sugandha B SB   Starzl Thomas E TE   Trucco Massimo M  

The Journal of biological chemistry 20011228 12


Galactose-alpha1,3-galactose (alphaGal) epitopes, the synthesis of which requires the enzyme product of alpha1,3-galactosyltransferase (alpha1,3GT), are sugar chains on the cell surface of most mammalian species. Notable exceptions are higher primates including Old World monkeys, apes, and humans. The alphaGal-negative species as well as mice with deletion of the alpha1,3GT gene produce abundant anti-alphaGal antibodies. The evolutionary loss of alphaGal epitopes has been attributed to point mut  ...[more]

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