A Genome-wide Survey of Human Pseudogenes

Overview

Journal Genome Res

Specialty Genetics

Date 2003 Dec 6

PMID 14656963

Citations 120

Authors

David Torrents

Mikita Suyama

Evgeny Zdobnov

Peer Bork

Affiliations

Soon will be listed here.

Abstract

We screened all intergenic regions in the human genome to identify pseudogenes with a combination of homology searches and a functionality test using the ratio of silent to replacement nucleotide substitutions (KA/KS). We identified 19,724 regions of which 95% +/- 3% are estimated to evolve neutrally and thus are likely to encode pseudogenes. Half of these have no detectable truncation in their pseudocoding regions and therefore are not identifiable by methods that require the presence of truncations to prove nonfunctionality. A comparative analysis with the mouse genome showed that 70% of these pseudogenes have a retrotranspositional origin (processed), and the rest arose by segmental duplication (nonprocessed). Although the spread of both types of pseudogenes correlates with chromosome size, nonprocessed pseudogenes appear to be enriched in regions with high gene density. It is likely that the human pseudogenes identified here represent only a small fraction of the total, which probably exceeds the number of genes.

Citing Articles

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Functional Characterization of a Phf8 Processed Pseudogene in the Mouse Genome.

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References

Mounsey A, Bauer P, Hope I . Evidence suggesting that a fifth of annotated Caenorhabditis elegans genes may be pseudogenes. Genome Res. 2002; 12(5):770-5. PMC: 186578. DOI: 10.1101/gr.208802. View

Birney E, Durbin R . Dynamite: a flexible code generating language for dynamic programming methods used in sequence comparison. Proc Int Conf Intell Syst Mol Biol. 1997; 5:56-64. View

Zhang Z, Harrison P, Gerstein M . Identification and analysis of over 2000 ribosomal protein pseudogenes in the human genome. Genome Res. 2002; 12(10):1466-82. PMC: 187539. DOI: 10.1101/gr.331902. View

Prince V, Pickett F . Splitting pairs: the diverging fates of duplicated genes. Nat Rev Genet. 2002; 3(11):827-37. DOI: 10.1038/nrg928. View

Waterston R, Lindblad-Toh K, Birney E, Rogers J, Abril J, Agarwal P . Initial sequencing and comparative analysis of the mouse genome. Nature. 2002; 420(6915):520-62. DOI: 10.1038/nature01262. View

Pavlicek A, Paces J, Zika R, Hejnar J . Length distribution of long interspersed nucleotide elements (LINEs) and processed pseudogenes of human endogenous retroviruses: implications for retrotransposition and pseudogene detection. Gene. 2002; 300(1-2):189-94. DOI: 10.1016/s0378-1119(02)01047-8. View

Mulder N, Apweiler R, Attwood T, Bairoch A, Barrell D, Bateman A . The InterPro Database, 2003 brings increased coverage and new features. Nucleic Acids Res. 2003; 31(1):315-8. PMC: 165493. DOI: 10.1093/nar/gkg046. View

Collins J, Goward M, Cole C, Smink L, Huckle E, Knowles S . Reevaluating human gene annotation: a second-generation analysis of chromosome 22. Genome Res. 2003; 13(1):27-36. PMC: 430954. DOI: 10.1101/gr.695703. View

Menashe I, Man O, Lancet D, Gilad Y . Different noses for different people. Nat Genet. 2003; 34(2):143-4. DOI: 10.1038/ng1160. View

10.

Hillier L, Fulton R, Fulton L, Graves T, Pepin K, Wagner-McPherson C . The DNA sequence of human chromosome 7. Nature. 2003; 424(6945):157-64. DOI: 10.1038/nature01782. View

11.

Kimura M . Evolutionary rate at the molecular level. Nature. 1968; 217(5129):624-6. DOI: 10.1038/217624a0. View

12.

Li W, Gojobori T, Nei M . Pseudogenes as a paradigm of neutral evolution. Nature. 1981; 292(5820):237-9. DOI: 10.1038/292237a0. View

13.

Vanin E . Processed pseudogenes: characteristics and evolution. Annu Rev Genet. 1985; 19:253-72. DOI: 10.1146/annurev.ge.19.120185.001345. View

14.

Thompson J, Higgins D, Gibson T . CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994; 22(22):4673-80. PMC: 308517. DOI: 10.1093/nar/22.22.4673. View

15.

Ohta T, Ina Y . Variation in synonymous substitution rates among mammalian genes and the correlation between synonymous and nonsynonymous divergences. J Mol Evol. 1995; 41(6):717-20. DOI: 10.1007/BF00173150. View

16.

Yang Z . PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci. 1997; 13(5):555-6. DOI: 10.1093/bioinformatics/13.5.555. View

17.

Cost G, Boeke J . Targeting of human retrotransposon integration is directed by the specificity of the L1 endonuclease for regions of unusual DNA structure. Biochemistry. 1999; 37(51):18081-93. DOI: 10.1021/bi981858s. View

18.

Brosius J . RNAs from all categories generate retrosequences that may be exapted as novel genes or regulatory elements. Gene. 1999; 238(1):115-34. DOI: 10.1016/s0378-1119(99)00227-9. View

19.

Mighell A, Smith N, Robinson P, Markham A . Vertebrate pseudogenes. FEBS Lett. 2000; 468(2-3):109-14. DOI: 10.1016/s0014-5793(00)01199-6. View

20.

Goncalves I, Duret L, Mouchiroud D . Nature and structure of human genes that generate retropseudogenes. Genome Res. 2000; 10(5):672-8. PMC: 310883. DOI: 10.1101/gr.10.5.672. View