Abstract
While some pseudogenes have been reported to play important roles in gene regulation, little is known about the possible relationship between pseudogene functions and evolutionary process of pseudogenes, or about the forces responsible for the pseudogene evolution. In this study, we characterized human processed pseudogenes in terms of evolutionary dynamics. Our results show that pseudogenes tend to evolve toward: lower GC content, strong dinucleotide bias, reduced abundance of transcription factor binding motifs and short palindromes, and decreased ability to form nucleosomes. We explored possible evolutionary forces that shaped the evolution pattern of pseudogenes, and concluded that mutations in pseudogenes are likely determined, at least partially, by neighbor-dependent mutational bias and recombination-associated selection.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Arndt, P.F., and Hwa, T. (2005). Identification and measurement of neighbor-dependent nucleotide substitution processes. Bioinformatics 21, 2322–2328.
Babiarz, J.E., Ruby, J.G., Wang, Y., Bartel, D.P., and Blelloch, R. (2008). Mouse ES cells express endogenous shRNAs, siRNAs, and other microprocessor-independent, Dicer-dependent small RNAs. Genes Dev 22, 2773–2785.
Balakirev, E.S., and Ayala, F.J. (2003). Pseudogenes: are they “junk” or functional DNA? Annu Rev Genet 37, 123–151.
Bourque, G., Leong, B., Vega, V.B., Chen, X., Lee, Y.L., Srinivasan, K.G., Chew, J.L., Ruan, Y., Wei, C.L., Ng, H.H., and Liu, E.T. (2008). Evolution of the mammalian transcription factor binding repertoire via transposable elements. Genome Res 18, 1752–1762.
Broderick, J.A., and Zamore, P.D. (2014). Competitive endogenous RNAs cannot alter microRNA function in vivo. Mol Cell 54, 711–713.
Chen, J., and Xue, Y. (2016). Emerging roles of non-coding RNAs in epigenetic regulation. Sci China Life Sci 59, 227–235.
Denzler, R., Agarwal, V., Stefano, J., Bartel, D.P., and Stoffel, M. (2014). Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance. Mol Cell 54, 766–776.
de Souza, F.S., Franchini, L.F., and Rubinstein, M. (2013). Exaptation of transposable elements into novel cis-regulatory elements: is the evidence always strong? Mol Biol Evol 30, 1239–1251.
Doolittle, W.F. (2013). Is junk DNA bunk? A critique of ENCODE. Proc Natl Acad Sci USA 110, 5294–5300.
Ecker, J.R., Bickmore, W.A., Barroso, I., Pritchard, J.K., Gilad, Y., and Segal, E. (2012). Genomics: ENCODE explained. Nature 489, 52–55.
Eddy, S.R. (2013). The ENCODE project: missteps overshadowing a success. Curr Biol 23, R259–R261.
Eddy, S.R. (2012). The C-value paradox, junk DNA and ENCODE. Curr Biol 22, R898–R899.
Esnault, C., Maestre, J., and Heidmann, T. (2000). Human LINE retrotransposons generate processed pseudogenes. Nat Genet 24, 363–367.
Graur, D., Zheng, Y., Price, N., Azevedo, R.B.R., Zufall, R.A., and Elhaik, E. (2013). On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of ENCODE. Genome Biol Evol 5, 578–590.
Guo, X., Zhang, Z., Gerstein, M.B., and Zheng, D. (2009). Small RNAs originated from pseudogenes: cis-or trans-acting? PLoS Comput Biol 5, e1000449.
Han, Y.J., Ma, S.F., Yourek, G., Park, Y.D., and Garcia, J.G. (2011). A transcribed pseudogene of MYLK promotes cell proliferation. FASEB J 25, 2305–2312.
Harrison, P.M., Echols, N., and Gerstein, M.B. (2001). Digging for dead genes: an analysis of the characteristics of the pseudogene population in the Caenorhabditis elegans genome. Nucleic Acids Res 29, 818–830.
Harrison, P.M., Milburn, D., Zhang, Z., Bertone, P., and Gerstein, M. (2003). Identification of pseudogenes in the Drosophila melanogaster genome. Nucleic Acids Res 31, 1033–1037.
Hiratsu, K., Mochizuki, S., and Kinashi, H. (2000). Cloning and analysis of the replication origin and the telomeres of the large linear plasmid pSLA2-L in Streptomyces rochei. Mol Gen Genet 263, 1015–1021.
Hirotsune, S., Yoshida, N., Chen, A., Garrett, L., Sugiyama, F., Takahashi, S., Yagami, K., Wynshaw-Boris, A., and Yoshiki, A. (2003). An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene. Nature 423, 91–96.
Jacq, C., Miller, J.R., and Brownlee, G.G. (1977). A pseudogene structure in 5S DNA of Xenopus laevis. Cell 12, 109–120.
Khelifi, A., Duret, L., and Mouchiroud, D. (2005). HOPPSIGEN: a database of human and mouse processed pseudogenes. Nucleic Acids Res 33, D59–D66.
Kaplan, N., Moore, I.K., Fondufe-Mittendorf, Y., Gossett, A.J., Tillo, D., Field, Y., LeProust, E.M., Hughes, T.R., Lieb, J.D., Widom, J., and Segal, E. (2009). The DNA-encoded nucleosome organization of a eukaryotic genome. Nature 458, 362–366.
Kel, A.E., Goessling, E., Reuter, I., Cheremushkin, E., Kel-Margoulis, O.V., and Wingender, E. (2003). Match (TM): a tool for searching transcription factor binding sites in DNA sequences. Nucleic Acids Res 31, 3576–3579.
Kent, W.J. (2002). BLAT—the BLAST-like alignment tool. Genome Res 12, 656–664.
Kimura, M. (1980). A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol 16, 111–120.
Kong, A., Gudbjartsson, D.F., Sainz, J., Jonsdottir, G.M., Gudjonsson, S.A., Richardsson, B., Sigurdardottir, S., Barnard, J., Hallbeck, B., Masson, G., Shlien, A., Palsson, S.T., Frigge, M.L., Thorgeirsson, T.E., Gulcher, J.R., and Stefansson, K. (2002). A high resolution recombination map of the human genome. Nat Genet 31, 241–247.
Korneev, S.A., Park, J.H., 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. J Neurosci 19, 7711–7720.
Kullback, S. (1959). Information Theory and Statistics. New York: Wiley.
Kumar, S., Tamura, K., and Nei, M. (2004). MEGA3: integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform 5, 150–163.
Lerat, E., and Ochman, H. (2005). Recognizing the pseudogenes in bacterial genomes. Nucleic Acids Res 33, 3125–3132.
Lisnic, B., Svetec, I.K., Saric, H., Nikolic, I., and Zgaga, Z. (2005). Palindrome content of the yeast Saccharomyces cerevisiae genome. Curr Genet 47, 289–297.
Liu, G., Liu, J., and Zhang, B. (2012). Compositional bias is a major determinant of the distribution pattern and abundance of palindromes in Drosophila melanogaster. J Mol Evol 72, 130–140.
Liu, G., Li, H., and Cai, L. (2010). Processed pseudogenes are located preferentially in regions of low recombination rates in the human genome. J Evol Biol 23, 1107–1115.
Liu, G., Feng, F., Zhao, X., and Cai, Lu. (2015). Nucleosome organization around pseudogenes in the human genome. BioMed Res Int 2015, 821596.
Luo, L., Lee, W., Jia, L., Ji, F., and Tsai, L. (1998). Statistical correlation of nucleotides in a DNA sequence. Phys Rev E 58, 861–871.
Matys, V., Kel-Margoulis, O.V., Fricke, E., Liebich, I., Land, S., Barre-Dirrie, A., Reuter, I., Chekmenev, D., Krull, M., Hornischer, K., Voss, N., Stegmaier, P., Lewicki-Potapov, B., Saxel, H., Kel, A.E., and Wingender, E. (2006). TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes. Nucleic Acids Res. 34, D108–D110.
Morozov, A.V., Fortney, K., Gaykalova, D.A., Studitsky, V.M., Widom, J., and Siggia, E.D. (2009). Using DNA mechanics to predict in vitro nucleosome positions and formation energies. Nucleic Acids Res 37, 4707–4722.
Niu, D.K., and Jiang, L. (2013). Can ENCODE tell us how much junk DNA we carry in our genome? Biochem Biophys Res Commun 430, 1340–1343.
Palazzo, A.F., and Lee, E.S. (2015). Non-coding RNA: what is functional and what is junk? Front Genet 6, 2.
Paris, M., Kaplan, T., Li, X.Y., Villalta, J.E., Lott, S.E., and Eisen, M.B. (2013). Extensive divergence of transcription factor binding in Drosophila embryos with highly conserved gene expression. PLoS Genet 9, e1003748.
Pavlicek, A., Jabbari, K., Paces, J., Paces, V., Hejnar, J.V., and Bernardi, G. (2001). Similar integration but different stability of Alus and LINEs in the human genome. Gene 276, 39–45.
Pennisi, E. (2012). ENCODE project writes eulogy for junk DNA. Science 337, 1159–1161.
Piehler, A.P., Hellum, M., Wenzel, J.J., Kaminski, E., Haug, K.B., Kierulf, P., and Kaminski, W.E. (2008). The human ABC transporter pseudogene family: evidence for transcription and gene-pseudogene interference. BMC Genomics 9, 165.
Pink, R.C., Wicks, K., Caley, D.P., Punch, E.K., Jacobs, L., and Carter, D.R.F. (2011). Pseudogenes: pseudo-functional or key regulators in health and disease. RNA 17, 792–798.
Polak, P., Domany, E. (2006). Alu elements contain many binding sites for transcription factors and may play a role in regulation of developmental processes. BMC Genomics 7, 133.
Poliseno, L., Salmena, L., Zhang, J., Carver, B., Haveman, W.J., and Pandolfi, P.P. (2010). A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465, 1033–1038.
Richmond, T.J., and Davey, C.A. (2003). The structure of DNA in the nucleosome core. Nature 423, 145–150.
Segal, E., Fondufe-Mittendorf, Y., Chen, L., Thastrom, A., Field, Y., Moore, I.K., Wang, J.P., and Widom, J. (2006). A genomic code for nucleosome positioning. Nature 442, 772–778.
Singh, N.D., Arndt, P.F., and Petrov, D.A. (2005). Genomic heterogeneity of background substitutional patterns in Drosophila melanogaster. Genetics 169, 709–722.
Stergachis, A.B., Haugen, E., Shafer, A., Fu, W., Vernot, B., Reynolds, A., Raubitschek, A., Ziegler, S., LeProust, E.M., Akey, J.M., and Stamatoyannopoulos, J.A. (2013). Exonic transcription factor binding directs codon choice and affects protein evolution. Science 342, 1367–1372.
Su, M., Han, D., Boyd-Kirkup, J., Yu, X., Han, J.D.J. (2014). Evolution of Alu elements toward enhancers. Cell Rep 7, 376–385.
Tam, O.H., Aravin, A.A., Stein, P., Girard, A., Murchison, E.P., Cheloufi, S., Hodges, E., Anger, M., Sachidanandam, R., Schultz, R.M., and Hannon, G.J. (2008). Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453, 534–538.
Tay, Y., Kats, L., Salmena, L., Weiss, D., Tan, S.M., Ala, U., Karreth, F., Poliseno, L., Provero, P., Di Cunto, F., Lieberman, J., Rigoutsos, I., and Pandolfi, P.P. (2011). Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell 147, 344–357.
The ENCODE Project Consortium. (2012). An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74.
Thibaud-Nissen, F., Ouyang, S., and Buell, C.R. (2009). Identification and characterization of pseudogenes in the rice gene complement. BMC Genomics 10, 317.
Thukral, S.K., Eisen, A., and Young, E.T. (1991). Two monomers of yeast transcription factor ADR1 bind a palindromic sequence symmetrically to activate ADH2 expression. Mol Cell Biol 11, 1566–1577.
Tillo, D., and Hughes, T.R. (2009). G+C content dominates intrinsic nucleosome occupancy. BMC Bioinformatics 10, 442.
Wang, J.Y., Wang, J., and Liu, G. (2012). Calculation of nucleosomal DNA deformation energy: its implication for nucleosome positioning. Chromosome Res 20, 889–902.
Wang, M., Zhang, P., Shu, Y., Yuan, F., Zhang, Y., Zhou, Y., Jiang, M., Zhu, Y., Hu, L., Kong, X., and Zhang, Z. (2014). Alternative splicing at GYNNGY 5’ splice sites: more noise, less regulation. Nucleic Acids Res 42, 13969–13980.
Watanabe, T., Totoki, Y., Toyoda, A., Kaneda, M., Kuramochi-Miyagawa, S., Obata, Y., Chiba, H., Kohara, Y., Kono, T., Nakano, T., Surani, M.A., Sakaki, Y., and Sasaki, H. (2008). Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 453, 539–543.
Wei, L., and Cao, X. (2016). The effect of transposable elements on phenotypic variation: insights from plants to humans. Sci China Life Sci 59, 24–37
Wen, Y.Z., Zheng, L.L., Liao, J.Y., Wang, M.H., Wei, Y., Guo, X.M., Qu, L.H., Ayala, F.J., and Lun, Z.R. (2011). Pseudogene-derived small interference RNAs regulate gene expression in African Trypanosoma brucei. Proc Natl Acad Sci USA 108, 8345–8350.
Zhang, Z.D., Frankish, A., Hunt, T., Harrow, J., and Gerstein, M.B. (2010). Identification and analysis of unitary pseudogenes: historic and contemporary gene losses in humans and other primates. Genome Biol 11, R26.
Zhang, Z., and Gerstein, M. (2003). Patterns of nucleotide substitution, insertion and deletion in the human genome inferred from pseudogenes. Nucleic Acid Research 31, 5338–5348.
Zhang, Z., Harrison, P.M., Liu, Y., and Gerstein, M. (2003). Millions of years of evolution preserved: a comprehensive catalog of the processed pseudogenes in the human genome. Genome Res 13, 2541–2558.
Zhang, Z., Harrison, P., and Gerstein, M. (2002). Identification and analysis of over 2000 ribosomal protein pseudogenes in the human genome. Genome Res 12, 1466–1482.
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is published with open access at springerlink.fh-diploma.de
Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
About this article
Cite this article
Liu, G., Cui, X., Li, H. et al. Evolutionary direction of processed pseudogenes. Sci. China Life Sci. 59, 839–849 (2016). https://doi.org/10.1007/s11427-016-5074-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-016-5074-x