Abstract
BackgroundPseudogenes provide a record of the molecular evolution of genes. As glycolysis is such a highly conserved and fundamental metabolic pathway, the pseudogenes of glycolytic enzymes comprise a standardized genomic measuring stick and an ideal platform for studying molecular evolution. One of the glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), has already been noted to have one of the largest numbers of associated pseudogenes, among all proteins.ResultsWe assembled the first comprehensive catalog of the processed and duplicated pseudogenes of glycolytic enzymes in many vertebrate model-organism genomes, including human, chimpanzee, mouse, rat, chicken, zebrafish, pufferfish, fruitfly, and worm (available at ). We found that glycolytic pseudogenes are predominantly processed, i.e. retrotransposed from the mRNA of their parent genes. Although each glycolytic enzyme plays a unique role, GAPDH has by far the most pseudogenes, perhaps reflecting its large number of non-glycolytic functions or its possession of a particularly retrotranspositionally active sub-sequence. Furthermore, the number of GAPDH pseudogenes varies significantly among the genomes we studied: none in zebrafish, pufferfish, fruitfly, and worm, 1 in chicken, 50 in chimpanzee, 62 in human, 331 in mouse, and 364 in rat. Next, we developed a simple method of identifying conserved syntenic blocks (consistently applicable to the wide range of organisms in the study) by using orthologous genes as anchors delimiting a conserved block between a pair of genomes. This approach showed that few glycolytic pseudogenes are shared between primate and rodent lineages. Finally, by estimating pseudogene ages using Kimura's two-parameter model of nucleotide substitution, we found evidence for bursts of retrotranspositional activity approximately 42, 36, and 26 million years ago in the human, mouse, and rat lineages, respectively.ConclusionOverall, we performed a consistent analysis of one group of pseudogenes across multiple genomes, finding evidence that most of them were created within the last 50 million years, subsequent to the divergence of rodent and primate lineages.
Highlights
Pseudogenes provide a record of the molecular evolution of genes
After mRNAs of the parent genes are transcribed in the usual fashion by RNA polymerases, they are reverse transcribed and integrated into genomic DNA by reverse transcriptases and endonucleases encoded by long interspersed nuclear elements (LINEs) in primates and humans [14,15,5,16,17]
Pseudogene pipeline, as decribed under Methods, we found that the number of pseudogenes does not vary significantly with the threshold for sequence identity or BLAST score when compared to the parent gene
Summary
Pseudogenes provide a record of the molecular evolution of genes. As glycolysis is such a highly conserved and fundamental metabolic pathway, the pseudogenes of glycolytic enzymes comprise a standardized genomic measuring stick and an ideal platform for studying molecular evolution. Pseudogenes are inheritable genomic sequences sharing large amounts of sequence similarity to genes but exhibit limited or altered functionality because of disablements. After mRNAs of the parent genes are transcribed in the usual fashion by RNA polymerases, they are reverse transcribed and integrated into genomic DNA by reverse transcriptases and endonucleases encoded by long interspersed nuclear elements (LINEs) in primates and humans [14,15,5,16,17]. Because these pseudogenes are generated through mRNA intermediates, they are notable for their lack of introns, spliced out during mRNA maturation. They retain most of the exon-intron arrangements with possible duplication of upstream and downstream regions
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