HUMAN TESTIS-SPECIFIC PGK GENE LACKS INTRONS AND POSSESSES CHARACTERISTICS OF A PROCESSED GENE
HUMAN TESTIS-SPECIFIC PGK GENE LACKS INTRONS AND POSSESSES CHARACTERISTICS OF A PROCESSED GENE
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DOI：
10.1038/326501a0
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发表时间：
1987-04-02
期刊：
影响因子：
64.8
通讯作者：
THOMAS, K
中科院分区：
文献类型：
--
作者：
MCCARREY, JR;THOMAS, K
磷酸甘油酸激酶（PGK）（ATP：3-磷酸-D-甘油酸1-磷酸转移酶，EC 2.7.2.3）是在Embden-Meyerhof途径中起作用的代谢酶，其将葡萄糖（或果糖）转化为丙酮酸。PGK-1是一个X连锁的基因，在哺乳动物的体细胞和减数分裂前生殖细胞中组成型表达1 -4。人PGK-1基因由11个外显子和10个内含子组成，包含一个长度为23 kb的区域5.PGK-2是一个常染色体基因，仅在精子发生的晚期以组织特异性方式表达3，4，6-8。在本研究中，对最初由Szabo等人分离的PGK-2的人类基因组克隆进行的分子分析显示，该常染色体序列完全缺乏内含子，并含有加工基因的特征10，11，或“逆转录酶”12，13，包括poly（A）+尾的残留物和边界直接重复序列。典型地，这样的加工序列形成非功能性假基因，其已经进化出多个遗传损伤，其阻止任何转录物翻译成功能性多肽10。例如，已经鉴定出人类PGK-1的X-连锁加工假基因（PGK-1），并显示其在所有阅读框中都含有提前终止密码子14。因此，我们意外地发现，这里报道的无内含子常染色体PGK序列不是假基因，而是一个保留了完整开放阅读框架的功能基因，并且在哺乳动物精子发生中活跃表达。PGK-2基因在精子发生过程中的功能异常保守性及其组织特异性表达可以解释为对减数分裂前生精细胞中X连锁PGK-1基因失活的补偿反应。
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-1is an X-linked gene expressed constitutively in all somatic cells and premeitotic germ cells1–4.. The humanPGK-1gene consists of 11 exons and 10 introns encompassing a region ∼23 kilobases (kb) in length5.PGK-2is an autosomal gene expressed in a tissue-specific manner exclusively in the late stages of spermatogenesis3,4,6–8. In the present study, a molecular analysis of a human genomic clone ofPGK-2originally isolated by Szabo et al.9has revealed that this autosomal sequence completely lacks introns and contains characteristics of a processed gene10,11, 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 ofPGK-1(ψPGK-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 autosomalPGKsequence 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 processedPGK-2gene and its tissue-specific expression in spermatogenesis are best explained as a compensatory response to the inactivation of the X-linkedPGK-1gene in spermatogenic cells before meiosis.