Abstract
Processed pseudogenes are a curious feature of genomes in higher organisms: copies of gene sequences without the associated introns or regulatory sequences. Annotation of assembled genomes has indicated many thousands of processed pseudogenes, and many subsequent studies have shown them to be highly important material for the evolution of new genes, suggesting that the term ‘pseudogene’ is often a misnomer. It has been shown that these copies arise through non-LTR retrotransposition mediated by LINE-1 elements which also mobilise a host of other sequences, and thus they are sometimes referred to as ‘gene retrocopies’ or ‘retrogenes’. Recent research has identified cases where novel gene retrocopies have consequences in terms of phenotypic variation and genetic disease, and multiple studies have surveyed the extent of gene retrocopy insertion polymorphism in humans and other species. Finally, in line with the biology of other retrotransposons, gene retrocopy insertions can exist as somatic mutations, suggesting an interesting though yet unproven mechanism for their occasional involvement in cancer etiology.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abyzov A et al (2013) Analysis of variable retroduplications in human populations suggests coupling of retrotransposition to cell division. Genome Res 23(12):2042–2052
Alkan C, Sajjadian S, Eichler EE (2011) Limitations of next-generation genome sequence assembly. Nat Methods 8(1):61–65
Altschul SF et al (1990) Basic local alignment search tool. J Mol Biol 215(3):403–410
Baertsch R et al (2008) Retrocopy contributions to the evolution of the human genome. BMC Genomics 9:466
Bradley J et al (2004) An X-to-autosome retrogene is required for spermatogenesis in mice. Nat Genet 36(8):872–876
Britten RJ, Kohne DE (1968) Repeated sequences in DNA. Hundreds of thousands of copies of DNA sequences have been incorporated into the genomes of higher organisms. Science 161(3841):529–540
Carelli FN et al (2016) The life history of retrocopies illuminates the evolution of new mammalian genes. Genome Res 26(3):301–314. doi:10.1101/gr.198473.115
Colgan DF, Manley JL (1997) Mechanism and regulation of mRNA polyadenylation. Genes Dev 11(21):2755–2766
Conrad DF et al (2009) Origins and functional impact of copy number variation in the human genome. Nature 464(7289):704–712
Cooke SL et al (2014) Processed pseudogenes acquired somatically during cancer development. Nat Commun 5:3644
Cordaux R et al (2006) Estimating the retrotransposition rate of human Alu elements. Gene 373:134–137
de Boer M et al (2014) Primary immunodeficiency caused by an exonized retroposed gene copy inserted in the CYBB gene. Hum Mutat 35(4):486–496
Dewannieux M, Esnault C, Heidmann T (2003) LINE-mediated retrotransposition of marked Alu sequences. Nat Genet 35(1):41–48
Doucet AJ et al (2015) A 3′ Poly(A) tract is required for LINE-1 retrotransposition. Mol Cell 60(5):728–741
Emerson JJ, Kaessmann H, Betrán E et al (2004) Extensive gene traffic on the mammalian X chromosome. Science 303(5657):537–540
Esnault C, Maestre J, Heidmann T (2000) Human LINE retrotransposons generate processed pseudogenes. Nat Genet 24(4):363–367
Ewing AD (2015) Transposable element detection from whole genome sequence data. Mob DNA 6:24
Ewing AD, Kazazian HH (2010) High-throughput sequencing reveals extensive variation in human-specific L1 content in individual human genomes. Genome Res 20(9):1262–1270
Ewing AD et al (2013) Retrotransposition of gene transcripts leads to structural variation in mammalian genomes. Genome Biol 14(3):R22
Gilad Y, Man O, Glusman G (2005) A comparison of the human and chimpanzee olfactory receptor gene repertoires. Genome Res 15(2):224–230
Glusman G et al (2001) The complete human olfactory subgenome. Genome Res 11(5):685–702
Hancks DC, Kazazian HH Jr (2012) Active human retrotransposons: variation and disease. Curr Opin Genet Dev 22(3):191–203
Hancks DC et al (2011) Retrotransposition of marked SVA elements by human L1s in cultured cells. Hum Mol Genet 20(17):3386–3400
Hirotsune S et al (2003) An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene. Nature 423(6935):91–96
Huang CRL et al (2010) Mobile interspersed repeats are major structural variants in the human genome. Cell 141(7):1171–1182
Hurteau GJ, Spivack SD (2002) mRNA-specific reverse transcription-polymerase chain reaction from human tissue extracts. Anal Biochem 307(2):304–315
International Chicken Genome Sequencing Consortium (2004) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432(7018):695–716
Jacq C, Miller JR, Brownlee GG (1977) A pseudogene structure in 5S DNA of Xenopus laevis. Cell 12(1):109–120
Jurka J et al (2005) Repbase Update, a database of eukaryotic repetitive elements. Cytogenet Genome Res 110(1–4):462–467
Kabza M et al (2015) Inter-population differences in retrogene loss and expression in humans. PLoS Genet 11(10):e1005579
Kaessmann H, Vinckenbosch N, Long M (2009) RNA-based gene duplication: mechanistic and evolutionary insights. Nat Rev Genet 10(1):19–31
Kalyana-Sundaram S et al (2012) Expressed pseudogenes in the transcriptional landscape of human cancers. Cell 149(7):1622–1634
Karakoc E et al (2012) Detection of structural variants and indels within exome data. Nat Methods 9(2):176–178
Karro JE et al (2007) Pseudogene.org: a comprehensive database and comparison platform for pseudogene annotation. Nucleic Acids Res 35(Database issue):D55–D60
Kazazian HH et al (1988) Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man. Nature 332(6160):164–166
Korneev SA, Park JH, O’Shea M (1999) Neuronal expression of neural nitric oxide synthase (nNOS) protein is suppressed by an antisense RNA transcribed from an NOS pseudogene. J Neurosci 19(18):7711–7720
Kuhn A et al (2014) Linkage disequilibrium and signatures of positive selection around LINE-1 retrotransposons in the human genome. Proc Natl Acad Sci U S A 111(22):8131–8136
Kulpa DA, Moran JV (2006) Cis-preferential LINE-1 reverse transcriptase activity in ribonucleoprotein particles. Nat Struct Mol Biol 13(7):655–660
Lam HYK et al (2010) Nucleotide-resolution analysis of structural variants using BreakSeq and a breakpoint library. Nat Biotechnol 28(1):47–55
Lander ES et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921
Liu Y-J et al (2009) 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. BMC Genomics 10:480
Long M, Langley CH (1993) Natural selection and the origin of jingwei, a chimeric processed functional gene in Drosophila. Science 260(5104):91–95
Luan DD et al (1993) Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: a mechanism for non-LTR retrotransposition. Cell 72(4):595–605
Marques AC et al (2005) Emergence of young human genes after a burst of retroposition in primates. PLoS Biol 3(11):e357
McCarrey JR, Thomas K (1987) Human testis-specific PGK gene lacks introns and possesses characteristics of a processed gene. Nature 326(6112):501–505
Menon RS et al (1991) RT-PCR artifacts from processed pseudogenes. PCR Methods Appl 1(1):70–71
Mighell AJ et al (2000) Vertebrate pseudogenes. FEBS Lett 468(2–3):109–114
Moran JV et al (1996) High frequency retrotransposition in cultured mammalian cells. Cell 87(5):917–927
Mouse Genome Sequencing Consortium et al (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420(6915):520–562
Navarro FCP, Galante PAF (2015) A genome-wide landscape of retrocopies in primate genomes. Genome Biol Evol 7(8):2265–2275
Nisole S et al (2004) A Trim5-cyclophilin A fusion protein found in owl monkey kidney cells can restrict HIV-1. Proc Natl Acad Sci U S A 101(36):13324–13328
Ohno S (1970) Evolution by gene duplication. Springer, Berlin
Parker HG et al (2009) An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science 325(5943):995–998
Pavlícek A et al (2002) Length distribution of long interspersed nucleotide elements (LINEs) and processed pseudogenes of human endogenous retroviruses: implications for retrotransposition and pseudogene detection. Gene 300(1–2):189–194
Pevzner PA, Tang H, Waterman MS (2001) An Eulerian path approach to DNA fragment assembly. Proc Natl Acad Sci U S A 98(17):9748–9753
Poliseno L et al (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465(7301):1033–1038
Potrzebowski L et al (2008) Chromosomal gene movements reflect the recent origin and biology of therian sex chromosomes. PLoS Biol 6(4):e80
Raiz J et al (2012) The non-autonomous retrotransposon SVA is trans-mobilized by the human LINE-1 protein machinery. Nucleic Acids Res 40(4):1666–1683
Richardson SR, Salvador-Palomeque C, Faulkner GJ (2014) Diversity through duplication: whole-genome sequencing reveals novel gene retrocopies in the human population. Bioessays 36(5):475–481
Rohozinski J, Bishop CE (2004) The mouse juvenile spermatogonial depletion (jsd) phenotype is due to a mutation in the X-derived retrogene, mUtp14b. Proc Natl Acad Sci U S A 101(32):11695–11700
Rohozinski J, Lamb DJ, Bishop CE (2006) UTP14c is a recently acquired retrogene associated with spermatogenesis and fertility in man. Biol Reprod 74(4):644–651
Sayah DM et al (2004) Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1. Nature 430(6999):569–573
Schrider DR, Stevens K et al (2011a) Genome-wide analysis of retrogene polymorphisms in Drosophila melanogaster. Genome Res 21(12):2087–2095
Schrider DR, Gout J-F, Hahn MW (2011b) Very few RNA and DNA sequence differences in the human transcriptome. PLoS One 6(10):e25842
Schrider DR et al (2013) Gene copy-number polymorphism caused by retrotransposition in humans. PLoS Genet 9(1):e1003242
Stewart C et al (2011) A comprehensive map of mobile element insertion polymorphisms in humans. PLoS Genet 7(8):e1002236
Sudmant PH et al (2015) An integrated map of structural variation in 2,504 human genomes. Nature 526(7571):75–81
Suh A (2015) The specific requirements for CR1 retrotransposition explain the scarcity of retrogenes in birds. J Mol Evol 81(1–2):18–20
Tam OH et al (2008) Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453(7194):534–538
Torrents D et al (2003) A genome-wide survey of human pseudogenes. Genome Res 13(12):2559–2567
Vanin EF (1985) Processed pseudogenes: characteristics and evolution. Annu Rev Genet 19:253–272
Vinckenbosch N, Dupanloup I, Kaessmann H (2006) Evolutionary fate of retroposed gene copies in the human genome. Proc Natl Acad Sci U S A 103(9):3220–3225
Virgen CA et al (2008) Independent genesis of chimeric TRIM5-cyclophilin proteins in two primate species. Proc Natl Acad Sci U S A 105(9):3563–3568
Warren WC et al (2008) Genome analysis of the platypus reveals unique signatures of evolution. Nature 453(7192):175–183
Watanabe T et al (2008) Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 453(7194):539–543
Wen Y-Z et al (2011) Pseudogene-derived small interference RNAs regulate gene expression in African Trypanosoma brucei. Proc Natl Acad Sci U S A 108(20):8345–8350
Wilson SJ et al (2008) Independent evolution of an antiviral TRIMCyp in rhesus macaques. Proc Natl Acad Sci U S A 105(9):3557–3562
Xing J et al (2009) Mobile elements create structural variation: analysis of a complete human genome. Genome Res 19(9):1516–1526
Yap MW et al (2004) Trim5alpha protein restricts both HIV-1 and murine leukemia virus. Proc Natl Acad Sci U S A 101(29):10786–10791
Zhang Z, Gerstein M (2003) The human genome has 49 cytochrome c pseudogenes, including a relic of a primordial gene that still functions in mouse. Gene 312:61–72
Zhang Z, Harrison P, Gerstein M (2002) Identification and analysis of over 2000 ribosomal protein pseudogenes in the human genome. Genome Res 12(10):1466–1482
Zhang Z et al (2003) Millions of years of evolution preserved: a comprehensive catalog of the processed pseudogenes in the human genome. Genome Res 13(12):2541–2558
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this chapter
Cite this chapter
Ewing, A.D. (2017). The Mobilisation of Processed Transcripts in Germline and Somatic Tissues. In: Cristofari, G. (eds) Human Retrotransposons in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-48344-3_4
Download citation
DOI: https://doi.org/10.1007/978-3-319-48344-3_4
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-48343-6
Online ISBN: 978-3-319-48344-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)