title: Comparative analysis of pseudogenes across three phyla.
abstract: Pseudogenes are degraded fossil copies of genes. Here, we report a comparison of pseudogenes spanning three phyla, leveraging the completed annotations of the human, worm, and fly genomes, which we make available as an online resource. We find that pseudogenes are lineage specific, much more so than protein-coding genes, reflecting the different remodeling processes marking each organism's genome evolution. The majority of human pseudogenes are processed, resulting from a retrotranspositional burst at the dawn of the primate lineage. This burst can be seen in the largely uniform distribution of pseudogenes across the genome, their preservation in areas with low recombination rates, and their preponderance in highly expressed gene families. In contrast, worm and fly pseudogenes tell a story of numerous duplication events. In worm, these duplications have been preserved through selective sweeps, so we see a large number of pseudogenes associated with highly duplicated families such as chemoreceptors. However, in fly, the large effective population size and high deletion rate resulted in a depletion of the pseudogene complement. Despite large variations between these species, we also find notable similarities. Overall, we identify a broad spectrum of biochemical activity for pseudogenes, with the majority in each organism exhibiting varying degrees of partial activity. In particular, we identify a consistent amount of transcription (∼15%) across all species, suggesting a uniform degradation process. Also, we see a uniform decay of pseudogene promoter activity relative to their coding counterparts and identify a number of pseudogenes with conserved upstream sequences and activity, hinting at potential regulatory roles.
authors.affiliation: Program in Computational Biology and Bioinformatics and Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520;
authors.forename: Cristina
authors.initials: C
authors.lastname: Sisu
authors.affiliation: Program in Computational Biology and Bioinformatics and.
authors.forename: Baikang
authors.initials: B
authors.lastname: Pei
authors.affiliation: Program in Computational Biology and Bioinformatics and.
authors.forename: Jing
authors.initials: J
authors.lastname: Leng
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
authors.forename: Adam
authors.initials: A
authors.lastname: Frankish
authors.affiliation: Program in Computational Biology and Bioinformatics and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520;
authors.forename: Suganthi
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: Center for Biomolecular Science and Engineering, University of California, Santa Cruz, CA 95064; and.
authors.forename: Rachel
authors.initials: R
authors.lastname: Harte
authors.affiliation: Program in Computational Biology and Bioinformatics and.
authors.forename: Daifeng
authors.initials: D
authors.lastname: Wang
authors.affiliation: Program in Computational Biology and Bioinformatics and.
authors.forename: Michael
authors.initials: M
authors.lastname: Rutenberg-Schoenberg
authors.affiliation: Program in Computational Biology and Bioinformatics and.
authors.forename: Wyatt
authors.initials: W
authors.lastname: Clark
authors.affiliation: Center for Biomolecular Science and Engineering, University of California, Santa Cruz, CA 95064; and.
authors.forename: Mark
authors.initials: M
authors.lastname: Diekhans
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520;
authors.forename: Joel
authors.initials: J
authors.lastname: Rozowsky
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
authors.forename: Tim
authors.initials: T
authors.lastname: Hubbard
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
authors.forename: Jennifer
authors.initials: J
authors.lastname: Harrow
authors.affiliation: Program in Computational Biology and Bioinformatics and Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520; Department of Computer Science, Yale University, New Haven, CT 06511 mark@gersteinlab.org.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Gerstein
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D019143:Evolution, Molecular; D056726:Genetic Association Studies; D006801:Humans; D058977:Molecular Sequence Annotation; D010802:Phylogeny; D011401:Promoter Regions, Genetic / Q000235:genetics; D011544:Pseudogenes / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
keywords: functional genomics; genome annotation; transcriptomics