Nature 326, 501 - 505 (08 April 1987); doi:10.1038/326501a0

Human testis-specific PGK gene lacks introns and possesses characteristics of a processed gene

John R. McCarrey^*‡ & Kelwyn Thomas^†

^* Division of Biology, Beckman Research Institute of The City of Hope, Duarte, California 91010, USA
^†Department of Biology, California Institute of Technology, Pasadena, California 91125, USA
^‡Present address: The Division of Reproductive Biology, Department of Population Dynamics, School of Hygiene and Public Health, The Johns Hopkins University, 615 N, Wolfe Street, Baltimore, Maryland 21205, USA.

Phosphoglycerate kinase (PGK) (ATP: 3-phospho-D-glycerate 1-phosphotransferase, EC 2.7.2.3) is a metabolic enzyme functioning in the Embden–Meyerhof pathway that converts glucose (or fructose) to pyruvate. Two functional loci for the production of PGK have been identified in the mammalian genome. PGK-1 is an X-linked gene expressed constitutively in all somatic cells and premeitotic germ cells^1–4.. The human PGK-1 gene consists of 11 exons and 10 introns encompassing a region 23 kilobases (kb) in length⁵. PGK-2 is an autosomal gene expressed in a tissue-specific manner exclusively in the late stages of spermatogenesis^3,4,6–8. In the present study, a molecular analysis of a human genomic clone of PGK-2 originally isolated by Szabo et al.⁹ has revealed that this autosomal sequence completely lacks introns and contains characteristics of a processed gene^10,11, or 'retroposon'^12,13, including the remnants of a poly(A)⁺ tail and bounding direct repeats. Typically such processed sequences form non-functional pseudogenes that have evolved multiple genetic lesions which preclude translation of any transcript into a functional polypeptide¹⁰. For example, an X-linked processed pseudogene of PGK-1 (PGK-1) in humans has been identified and shown to contain premature termination codons in all reading frames¹⁴. It was therefore unexpected to find that the intronless autosomal PGK sequence reported here is not a pseudogene, but is rather a functional gene that has retained a complete open reading frame, and is actively expressed in mammalian spermatogenesis. Both the unusual conservation of function in this processed PGK-2 gene and its tissue-specific expression in spermatogenesis are best explained as a compensatory response to the inactivation of the X-linked PGK-1 gene in spermatogenic cells before meiosis.

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