Alu -mediated inactivation of the human CMP- N -acetylneuraminic acid hydroxylase gene

doi:10.1073/pnas.191268198

Alu-mediated inactivation of the human CMP- N-acetylneuraminic acid hydroxylase gene

^*Department of Biosystems Science, Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa 240-0193, Japan; and ^†Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093-0687

Edited by Henry C. Harpending, University of Utah, Salt Lake City, UT, July 17, 2001 (received for review May 30, 2001)

Abstract

Inactivation of the CMP-N-acetylneuraminic acid hydroxylase gene has provided an example of human-specific genomic mutation that results in a widespread biochemical difference between human and nonhuman primates. We have found that, although a region containing a 92-bp exon and an AluSq element in the hydroxylase gene is intact in all nonhuman primates examined, the same region in the human genome is replaced by an AluY element that was disseminated at least one million years ago. We propose a mechanistic model for this Alu-mediated replacement event, which deleted the 92-bp exon and thus inactivated the human hydroxylase gene. It is suggested that Alu elements have played potentially important roles in genotypic and phenotypic evolution in the hominid lineage.

Footnotes

↵ ‡ To whom reprint requests should be addressed. E-mail: takahata{at}soken.ac.jp.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database [accession nos. AB060157 (human genomic region around the 92-bp exon of CMP-Neu5Ac hydroxylase), AB060158 (chimpanzee genomic region around the 92-bp exon of CMP-Neu5Ac hydroxylase), AB060159 (gorilla genomic region around the 92-bp exon of CMP-Neu5Ac hydroxylase), and AB060160 (rhesus monkey genomic region around the 92-bp exon of CMP-Neu5Ac hydroxylase)].
Abbreviations:

Neu5Ac,

N-acetylneuraminic acid;

Neu5Gc,

N-glycolylneuraminic acid;

sahAluSq,

sialic acid hydroxylase AluSq;

sahAluY,

sialic acid hydroxylase AluY;

msAluY,

most similar AluY;

E-A region,

exon to AluSq region