36
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Comprehensive analysis of the pseudogenes of glycolytic enzymes in vertebrates: the anomalously high number of GAPDH pseudogenes highlights a recent burst of retrotrans-positional activity

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          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. 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.

          Results

          We 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 http://pseudogene.org/glycolysis/). 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.

          Conclusion

          Overall, 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.

          Related collections

          Most cited references46

          • Record: found
          • Abstract: found
          • Article: not found

          Genome sequence of the nematode C. elegans: a platform for investigating biology.

          (1999)
          The 97-megabase genomic sequence of the nematode Caenorhabditis elegans reveals over 19,000 genes. More than 40 percent of the predicted protein products find significant matches in other organisms. There is a variety of repeated sequences, both local and dispersed. The distinctive distribution of some repeats and highly conserved genes provides evidence for a regional organization of the chromosomes.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Human LINE retrotransposons generate processed pseudogenes.

            Long interspersed elements (LINEs) are endogenous mobile genetic elements that have dispersed and accumulated in the genomes of higher eukaryotes via germline transposition, with up to 100,000 copies in mammalian genomes. In humans, LINEs are the major source of insertional mutagenesis, being involved in both germinal and somatic mutant phenotypes. Here we show that the human LINE retrotransposons, which transpose through the reverse transcription of their own transcript, can also mobilize transcribed DNA not associated with a LINE sequence by a process involving the diversion of the LINE enzymatic machinery by the corresponding mRNA transcripts. This results in the 'retroposition' of the transcribed gene and the formation of new copies that disclose features characteristic of the widespread and naturally occurring processed pseudogenes: loss of intron and promoter, acquisition of a poly(A) 3' end and presence of target-site duplications of varying length. We further show-by introducing deletions within either coding sequence of the human LINE-that both ORFs are necessary for the formation of the processed pseudogenes, and that retroviral-like elements are not able to produce similar structures in the same assay. Our results strengthen the unique versatility of LINEs as genome modellers.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The origin and evolution of model organisms.

              The phylogeny and timescale of life are becoming better understood as the analysis of genomic data from model organisms continues to grow. As a result, discoveries are being made about the early history of life and the origin and development of complex multicellular life. This emerging comparative framework and the emphasis on historical patterns is helping to bridge barriers among organism-based research communities.
                Bookmark

                Author and article information

                Journal
                BMC Genomics
                BMC Genomics
                BioMed Central
                1471-2164
                2009
                16 October 2009
                : 10
                : 480
                Affiliations
                [1 ]Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Boston, MA, USA
                [2 ]Department of Molecular Biophysics and Biochemistry, P.O. Box 208114, Yale University, New Haven, CT 06520, USA
                [3 ]Albert Einstein College of Medicine of Yeshiva University, Department of Neurology, Rose F. Kennedy Center, 1410 Pelham Parkway South, Room 915B, Bronx, NY 10461, USA
                [4 ]Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA
                [5 ]Department of Computer Science, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA
                Article
                1471-2164-10-480
                10.1186/1471-2164-10-480
                2770531
                19835609
                1f3ea89c-331a-4290-b44b-ac7a88f53d89
                Copyright © 2009 Liu et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 March 2009
                : 16 October 2009
                Categories
                Research Article

                Genetics
                Genetics

                Comments

                Comment on this article