Unusual abundance of vertebrate 3-phosphate dehydrogenase pseudogenes

Nature (Impact Factor: 41.46). 11/1984; 312(5993):469-71. DOI: 10.1038/312786a0
Source: PubMed


Only one gene coding for glyceraldehyde 3-phosphate dehydrogenase (GAPDH, EC, a key enzyme in the control of glycolysis, is known to be functional in man, mouse, rat and chicken. The gene has been localized to chromosome 12 in human and chromosome 6 in mouse. Only a single mRNA species has been found in chicken and rat. However, analysis of genomic DNA blots of various species with a cloned GAPDH cDNA probe has revealed large differences in the level of reiteration, ranging from one to over 200 copies. On this basis, we have grouped these organisms into three classes according to the number of GAPDH-related sequences they contain; one class with a unique representation (chicken), another class of relatively low reiteration (10-30 copies in man, hare, guinea-pig and hamster) and a third class of high reiteration (greater than 200 copies in mouse and rat). The third class represents the first reported occurrence of such an extreme number of pseudogenes related to an enzyme-coding gene and suggests that a dramatic amplification event took place between 15 and 25 million years ago.

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    • "Pgk2 represent an ancient retrotransposition event shared by all eutherian mammals, while Aldoart1 and Aldoart2 are only found in the rodent lineage and are much more recent [4,28]. In addition, frequent retrotransposition of the Gapdh and Aldoa genes has been reported in both human and mouse, based on an abundance of pseudogenes [29-32]. "
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    ABSTRACT: The central metabolic pathway of glycolysis converts glucose to pyruvate, with the net production of 2 ATP and 2 NADH per glucose molecule. Each of the ten reactions in this pathway is typically catalyzed by multiple isozymes encoded by a multigene family. Several isozymes in this pathway are expressed only during spermatogenesis, and gene targeting studies indicate that they are essential for sperm function and male fertility in mouse. At least three of the novel glycolytic isozymes are encoded by retrogenes (Pgk2, Aldoart1, and Aldoart2). Their restricted expression profile suggests that retrotransposition may play a significant role in the evolution of sperm glycolytic enzymes. We conducted a comprehensive genomic analysis of glycolytic enzymes in the human and mouse genomes and identified several intronless copies for all enzymes in the pathway, except Pfk. Within each gene family, a single orthologous gene was typically retrotransposed frequently and independently in both species. Several retroposed sequences maintained open reading frames (ORFs) and/or provided evidence of alternatively spliced exons. We analyzed expression of sequences with ORFs and <99% sequence identity in the coding region and obtained evidence for the expression of an alternative Gpi1 transcript in mouse spermatogenic cells. Our analysis detected frequent, recent, and lineage-specific retrotransposition of orthologous glycolytic enzymes in the human and mouse genomes. Retrotransposition events are associated with LINE/LTR and genomic integration is random. We found evidence for the alternative splicing of parent genes. Many retroposed sequences have maintained ORFs, suggesting a functional role for these genes.
    BMC Genomics 05/2010; 11(1):285. DOI:10.1186/1471-2164-11-285 · 3.99 Impact Factor
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    • "Comparative genomics also demonstrates that the Smcp and Prm3 genes have not created retroposons in 16 and 12 species of mammals, respectively ([13] [18], Bagarova and Kleene, unpublished ) and Southern blots indicate that a variety of genes that are expressed specifically in meiotic and haploid spermatogenic cells are single copy [17]. The observation that the somatic glyceraldehyde-3′- phosphate dehydrogenase (GAPDH) mRNA has generated ~200 processed pseudogenes, while the spermatid-specific GAPDH mRNA has generated none [7] [29] [30], provides a striking example of the deficit in creation of retroposons from mRNAs that are expressed in haploid spermatogenic cells. Knockouts of the Mili2 and Dnmt3L genes reveal mechanisms that repress expression of LINE-1 retroposons in meiotic spermatogenic cells [31] [32], which probably suppress the creation of retroposons from cellular mRNAs [33]. "
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    ABSTRACT: The comparative genomics of the Odf1, Prm1, Prm2, Tnp1, and Tnp2 genes in 13-21 diverse mammalian species reveals striking similarities and differences in the sequences that probably function in the transcriptional and translational regulation of gene expression in haploid spermatogenic cells, spermatids. The 5' flanking regions contain putative TATA boxes and cAMP-response elements (CREs), but the TATA boxes and CREs exhibit gene-specific sequences, and an overwhelming majority of CREs differ from the consensus sequence. The 5' and 3' UTRs contain highly conserved gene-specific sequences including canonical and noncanonical poly(A) signals and a suboptimal context for the Tnp2 translation initiation codon. The conservation of the 5' UTR is unexpected because mRNA translation in spermatids is thought to be regulated primarily by the 3' UTR. Finally, all of the genes contain a single intron, implying that retroposons are rarely created from mRNAs that are expressed in spermatids.
    Genomics 09/2008; 92(2):101-6. DOI:10.1016/j.ygeno.2008.05.001 · 2.28 Impact Factor
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    • "There is evidence for an ancient duplication around the bilaterian origin; however, the testis-specific copy was found only in vertebrates, which makes this scenario rather unlikely. It has been hypothesized that vertebrates acquired a second copy, only expressed in the testis, by retroposition [84,85]. However, many more new gene copies were created, most of which, if not all, seem to be pseudogenes [42,86,87]. "
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