Abstract
CpG islands (CGIs) are aggregation of CpG dinucleotides in the promoters of mammalian genes. These CGIs are present in almost all the housekeeping genes and some tissue-specific genes in the mammalian genome. Extensive research has been done on the prevalence and role of CGIs in protein-coding genes. However, little is known about CGIs in pseudogenes. In the current research project, we focused on CGIs in three main classes of pseudogenes e.g., duplicated pseudogenes (DPGs), processed pseudogenes (PPGs), and unitary pseudogenes (UPGs). We discovered a predominant absence of CGIs in the promoters of all three pseudogenes. We also compared the CGI profile of these pseudogenes with their parent genes and found that unitary pseudogenes (UPGs) differ from the DPGs and PPGs in the sense that in the latter, lack of CGIs is a consequential event while in UPGs, this lack of CGIs in their promoters is not a result of pseudogenization process. We also discussed the implication of the results obtained from this comparison. To our knowledge, this is the first-ever study highlighting this aspect of UPGs throwing new insights into the evolution of genome in general and especially in the context of pseudogenes.
Similar content being viewed by others
References
Aken BL, Ayling S, Barrell D et al (2016) The ensembl gene annotation system. Database. https://doi.org/10.1093/database/baw093
Alberts B, Johnson A, Lewis J, et al (2007) Molecular biology of the cell
Antequera F (2003) Structure, function and evolution of CpG island promoters. Cell Mol Life Sci
Balakirev ES, Ayala FJ (2003) Pseudogenes: are they “Junk” or functional DNA? Annu Rev Genet 37
Bird AP (1980) DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res. https://doi.org/10.1093/nar/8.7.1499
Bird AP (1987) CpG islands as gene markers in the vertebrate nucleus. Trends Genet. https://doi.org/10.1016/0168-9525(87)90294-0
Cunningham F, Achuthan P, Akanni W et al (2019) Ensembl 2019. Nucleic Acids Res. https://doi.org/10.1093/nar/gky1113
Deaton AM, Bird A (2011) CpG islands and the regulation of transcription. Genes Dev. https://doi.org/10.1101/gad.2037511
Esnault C, Maestre J, Heidmann T (2000) Human LINE retrotransposons generate processed pseudogenes. Nat Genet. https://doi.org/10.1038/74184
Fatemi M, Pao MM, Jeong S et al (2005) Footprinting of mammalian promoters: use of a CpG DNA methyltransferase revealing nucleosome positions at a single molecule level. Nucleic Acids Res. https://doi.org/10.1093/nar/gni180
Gilbert SF, Ziony Z (2001) Congenital human baculum deficiency. Am J Med Genet 101
Illingworth RS, Bird AP (2009) CpG islands—“A rough guide.” FEBS Lett
Karro JE, Yan Y, Zheng D et al (2007) Pseudogene.org: a comprehensive database and comparison platform for pseudogene annotation. Nucleic Acids Res. https://doi.org/10.1093/nar/gkl851
Kinsella RJ, Kähäri A, Haider S et al (2011) Ensembl biomarts: a hub for data retrieval across taxonomic space. Database. https://doi.org/10.1093/database/bar030
Li WH, Gojobori T, Nei M (1981) Pseudogenes as a paradigm of neutral evolution. Nature. https://doi.org/10.1038/292237a0
Lynch M, Conery JS (2000) The evolutionary fate and consequences of duplicate genes. Science. https://doi.org/10.1126/science.290.5494.1151
Mighell AJ, Smith NR, Robinson PA, Markham AF (2000) Vertebrate pseudogenes. FEBS Lett
Pei B, Sisu C, Frankish A et al (2012) The GENCODE pseudogene resource. Genome Biol. https://doi.org/10.1186/gb-2012-13-9-r51
Ponger L, Mouchiroud D (2002) CpGProD: Identifying CpG islands associated with transcription start sites in large genomic mammalian sequences. Bioinformatics. https://doi.org/10.1093/bioinformatics/18.4.631
Saxonov S, Berg P, Brutlag DL (2006) A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.0510310103
Sen K, Podder S, Ghosh TC (2010) Insights into the genomic features and evolutionary impact of the genes configuring duplicated pseudogenes in human. FEBS Lett. https://doi.org/10.1016/j.febslet.2010.08.012
Sharif J, Endo TA, Toyoda T, Koseki H (2010) Divergence of CpG Island promoters: a consequence or cause of evolution? Dev Growth Differ. https://doi.org/10.1111/j.1440-169X.2010.01193.x
Sisu C, Pei B, Leng J et al (2014) Comparative analysis of pseudogenes across three phyla. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.1407293111
Subramanian S, Kumar S (2003) Neutral substitutions occur at a faster rate in exons than in noncoding DNA in primate genomes. Genome Res. https://doi.org/10.1101/gr.1152803
Swift ML (1997) GraphPad prism, data analysis, and scientific graphing. J Chem Inf Comput Sci
Torrents D, Suyama M, Zdobnov E, Bork P (2003) A genome-wide survey of human pseudogenes. Genome Res. https://doi.org/10.1101/gr.1455503
Vanin EF (1985) Processed pseudogenes: characteristics and evolution. Annu Rev Genet
Wu X, Lee CC, Muzny DM, Caskey CT (1989) Urate oxidase: primary structure and evolutionary implications. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.86.23.9412
Zhang Z, Gerstein M (2003) Patterns of nucleotide substitution, insertion and deletion in the human genome inferred from pseudogenes. Nucleic Acids Res. https://doi.org/10.1093/nar/gkg745
Zhang ZD, Frankish A, Hunt T et al (2010) Identification and analysis of unitary pseudogenes: historic and contemporary gene losses in humans and other primates. Genome Biol. https://doi.org/10.1186/gb-2010-11-3-r26
Author information
Authors and Affiliations
Contributions
AAK conceived the idea. AAK, MSA, FB, AF, MAS, BA, NA, MF, AU, and MAG collected the data. AAK, MSA, FB, AF, and MAS analyzed the data. AAK wrote the article.
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflict of interest to disclose.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Khan, A.A., Ali, M.S., Babar, F. et al. Lack of CpG islands in human unitary pseudogenes and its implication. Mamm Genome 32, 443–447 (2021). https://doi.org/10.1007/s00335-021-09893-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00335-021-09893-1