Pseudogenes and Their Evolution

Ondrej Podlaha, University of California, Davis, California, USA
Jianzhi Zhang, University of Michigan, Ann Arbor, Michigan, USA

Published online: November 2010

DOI: 10.1002/9780470015902.a0005118.pub2

Pseudogenes are relics of former genes that no longer possess biological functions. They are abundant in the genomes of complex organisms such as vertebrates and flowering plants and provide a useful resource for studying mutation rates and neutral evolutionary patterns. Processed pseudogenes can be regarded as fossilised footprints of past gene expression, permitting a peek into ancient transcriptomes. Occasionally adaptive, pseudogenisation is usually a neutral process. Yet, it can have a substantial impact on future evolution by limiting or opening certain evolutionary possibilities. Studies of pseudogenisation may help date key phenotypic changes in evolution and understand the genetic basis of phenotypic evolution. Recent studies found some pseudogenes to possess apparent functions in gene regulation, creating a difficulty in defining pseudogenes.

Key Concepts:

  • Pseudogenes are relatives of functional genes that have lost their functions.
  • Most pseudogenes arise from degenerated replicates of functional genes produced by either DNA-mediated gene duplication or RNA-mediated retroposition.
  • Processed pseudogenes arise from retroposition and their copy numbers are positively correlated with the germline expression levels of their parent genes. Thus, they may be regarded as fossilised footprints of past gene expression for studying ancient transcriptomes.
  • Most pseudogenes evolve neutrally and thus have been used to study the rates and patterns of mutations.
  • The human and mouse genomes contain nearly as many pseudogenes as functional genes.
  • The number of pseudogenes in a genome, compared to that of functional genes, varies substantially among organisms.
  • Pseudogenisation is usually a neutral process; yet, it can have significant impacts on future evolution by either limiting or opening certain evolutionary possibilities.
  • Pseudogenisation may occasionally be adaptive when the expression of a gene becomes deleterious, due to changes of the genetic background or environment.
  • Some apparent pseudogenes have been found to possess regulatory functions, causing a difficulty in defining pseudogenes.

Keywords: pseudogene; pseudogenisation; gene loss; evolution; gene regulation

Figure 1. Pseudogene formation after DNA- and RNA-mediated duplication. (a) Unequal crossing-over leads to the generation of an extra gene with a full complement of coding and noncoding sequences. (b) During retroposition, mature mRNA is reverse-transcribed and randomly inserted into the genome, giving rise to a processed pseudogene. Retroposition copies only the coding sequence, leaving out any regulatory sequence. Rectangles and bold lines represent exons and introns, respectively. Asterisks indicate open reading frame (ORF)-disrupting mutations. Reproduced with modification from Zhang (2003), with permission from Elsevier.
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 References
    Arabidopsis Genome Initiative (2000) Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408: 796–815.
    Balakirev ES and Ayala FJ (2003) Pseudogenes: are they “junk” or functional DNA? Annual Review of Genetics 37: 123–151.
    Balasubramanian S, Zheng D, Liu YJ et al. (2009) Comparative analysis of processed ribosomal protein pseudogenes in four mammalian genomes. Genome Biology 10: R2.
    Begun DJ (1997) Origin and evolution of a new gene descended from alcohol dehydrogenase in Drosophila. Genetics 145: 375–382.
    Benovoy D and Drouin G (2006) Processed pseudogenes, processed genes, and spontaneous mutations in the Arabidopsis genome. Journal of Molecular Evolution 62: 511–522.
    Blanc G, Hokamp K and Wolfe KH (2003) A recent polyploidy superimposed on older large-scale duplications in the Arabidopsis genome. Genome Research 13: 137–144.
    Dasilva C, Hadji H, Ozouf-Costaz C et al. (2002) Remarkable compartmentalization of transposable elements and pseudogenes in the heterochromatin of the Tetraodon nigroviridis genome. Proceedings of the National Academy of Sciences of the USA 99: 13636–13641.
    Eyal N, Wilder S and Horowitz M (1990) Prevalent and rare mutations among Gaucher patients. Gene 96: 277–283.
    Force A, Lynch M, Pickett FB et al. (1999) Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151: 1531–1545.
    Graur D, Shuali Y and Li WH (1989) Deletions in processed pseudogenes accumulate faster in rodents than in humans. Journal of Molecular Evolution 28: 279–285.
    Gray TA, Wilson A, Fortin PJ and Nicholls RD (2006) The putatively functional Mkrn1-p1 pseudogene is neither expressed nor imprinted, nor does it regulate its source gene in trans. Proceedings of the National Academy of Sciences of the USA 103: 12039–12044.
    Grus WE and Zhang J (2006) Origin and evolution of the vertebrate vomeronasal system viewed through system-specific genes. BioEssays 28: 709–718.
    Hirotsune S, Yoshida N, Chen A et al. (2003) An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene. Nature 423: 91–96.
    International Rice Genome Sequencing Project (2005) The map-based sequence of the rice genome. Nature 436: 793–800.
    Jacq C, Miller J and Brownlee G (1977) Pseudogene structure in 5S-DNA of Xenopus laevis. Cell 12: 109–120.
    Johnson JM, Edwards S, Shoemaker D and Schadt EE (2005) Dark matter in the genome: evidence of widespread transcription detected by microarray tiling experiments. Trends in Genetics 21: 93–102.
    Keren H, Lev-Maor G and Ast G (2010) Alternative splicing and evolution: diversification, exon definition and function. Nature Reviews. Genetics 11: 345–355.
    Korneev SA, Park JH and O'shea M (1999) Neuronal expression of neural nitric oxide synthase (nNOS) protein is suppressed by an antisense RNA transcribed from an NOS pseudogene. Journal of Neuroscience 19: 7711–7720.
    Marques AC, Dupanloup I, Vinckenbosch N, Reymond A and Kaessmann H (2005) Emergence of young human genes after a burst of retroposition in primates. PLoS Biology 3: e357.
    book Ohno S (1970) Evolution by Gene Duplication. Berlin: Springer.
    Ophir R and Graur D (1997) Patterns and rates of indel evolution in processed pseudogenes from humans and murids. Gene 205: 191–202.
    Ota T and Nei M (1995) Evolution of immunoglobulin VH pseudogenes in chickens. Molecular Biology and Evolution 12: 94–102.
    Petrov DA, Lozovskaya ER and Hartl DL (1996) High intrinsic rate of DNA loss in Drosophila. Nature 384: 346–349.
    Podlaha O and Zhang J (2009) Processed pseudogenes: the ‘fossilized footprints’ of past gene expression. Trends in Genetics 25: 429–434.
    Poliseno L, Salmena L, Zhang J et al. (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465: 1033–1038.
    Saleh M, Vaillancourt JP, Graham RK et al. (2004) Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms. Nature 429: 75–79.
    Shemesh R, Novik A, Edelheit S and Sorek R (2006) Genomic fossils as a snapshot of the human transcriptome. Proceedings of the National Academy of Sciences of the USA 103: 1364–1369.
    Stedman HH, Kozyak BW, Nelson A et al. (2004) Myosin gene mutation correlates with anatomical changes in the human lineage. Nature 428: 415–418.
    Tam O, Aravin A, Stein P et al. (2008) Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453: 534–538.
    Wang X, Grus WE and Zhang J (2006) Gene losses during human origins. PLoS Biology 4: e52.
    Watanabe T, Totoki Y, Toyoda A et al. (2008) Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 453: 539.
    Waterston RH, Lindblad-Toh K, Birney E et al. (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520–562.
    Watnick TJ, Gandolph MA, Weber H, Neumann HPH and Germino GG (1998) Gene conversion is a likely cause of mutation in PKD1. Human Molecular Genetics 7: 1239–1243.
    Yamada K, Lim J, Dale JM et al. (2003) Empirical analysis of transcriptional activity in the Arabidopsis genome. Science 302: 842–846.
    Yu J, Wang J, Lin W et al. (2005) The genomes of Oryza sativa: a history of duplications. PLoS Biology 3: e38.
    Zhang J (2003) Evolution by gene duplication – an update. Trends in Ecology & Evolution 18: 292–298.
    Zhang J and Webb DM (2003) Evolutionary deterioration of the vomeronasal pheromone transduction pathway in catarrhine primates. Proceedings of the National Academy of Sciences of the USA 100: 8337–8341.
    Zhang Z, Carriero N and Gerstein M (2004) Comparative analysis of processed pseudogenes in the mouse and human genomes. Trends in Genetics 20: 62–67.
    Zheng D and Gerstein MB (2007) The ambiguous boundary between genes and pseudogenes: the dead rise up, or do they? Trends in Genetics 23: 219–224.
    Zou C, Lehti-Shiu MD, Thibaud-Nissen F et al. (2009) Evolutionary and expression signatures of pseudogenes in Arabidopsis and rice. Plant Physiology 151: 3–15.
 Furthur Reading
    Chiefari E, Iiritano S, Paonessa F et al. (2010) Pseudogene-mediated posttranscriptional silencing of HMGA1 can result in insulin resistance and type 2 diabetes. Nature Communications 1: 40.
    Karro JE, Yan Y, Zheng D et al. (2007) Pseudogene. org: a comprehensive database and comparison platform for pseudogene annotation. Nucleic Acids Research 35: D55–D60.
    Lam HY, Khurana E, Fang G et al. (2009) Pseudofam: the pseudogene families database. Nucleic Acids Research 37: D738–D743.
    book Li WH (1997) Molecular Evolution. Sunderland, MA: Sinauer.
    Li WH, Gojobori T and Nei M (1981) Pseudogenes as a paradigm of neutral evolution. Nature 292: 237–239.
    Olson MV (1999) When less is more: gene loss as an engine of evolutionary change. American Journal of Human Genetics 64: 18–23.
    Svensson O, Arvestad L and Lagergren J (2006) Genome-wide survey for biologically functional pseudogenes. PLoS Computational Biology 2: e46.
    Zhang J and Zhang YP (2003) Pseudogenization of the tumor-growth promoter angiogenin in a leaf-eating monkey. Gene 308: 95–101.
    Zhao H, Yang JR, Xu H and Zhang J (2010) Pseudogenization of the umami taste receptor gene Tas1r1 in the giant panda coincided with its dietary switch to bamboo. Molecular Biology and Evolution [Epub ahead of print].

Related Sub-Topics:

Evolutionary Genomics | Molecular Evolution | Variation by Mutation and Recombination | DNA Structure and Function | Evolution of Coding and Functional Modules
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Article Title: Pseudogenes and Their Evolution
 
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Podlaha, Ondrej, and Zhang, Jianzhi(Nov 2010) Pseudogenes and Their Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005118.pub2]