Abstract
Imprinted genes exhibit silencing of one of the parental alleles during embryonic development. In a previous study imprinted genes were found to have reduced intron content relative to a non-imprinted control set (Hurst et al., 1996). However, due to the small sample size, it was not possible to analyse the source of this effect. Here, we re-investigate this observation using larger datasets of imprinted and control (non-imprinted) genes that allow us to consider mouse and human, and maternally and paternally silenced, imprinted genes separately. We find that, in the human and mouse, there is reduced intron content in the maternally silenced imprinted genes relative to a non-imprinted control set. Among imprinted genes, a strong bias is also observed in the distribution of intronless genes, which are found exclusively in the maternally silenced dataset. The paternally silenced dataset in the human is not different to the control set; however, the mouse paternally silenced dataset has more introns than the control group. A direct comparison of mouse maternally and paternally silenced imprinted gene datasets shows that they differ significantly with respect to a variety of intron-related parameters. We discuss a variety of possible explanations for our observations.
Full Text
The Full Text of this article is available as a PDF (182.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blagitko N., Mergenthaler S., Schulz U., Wollmann H. A., Craigen W., Eggermann T., Ropers H. H., Kalscheuer V. M. Human GRB10 is imprinted and expressed from the paternal and maternal allele in a highly tissue- and isoform-specific fashion. Hum Mol Genet. 2000 Jul 1;9(11):1587–1595. doi: 10.1093/hmg/9.11.1587. [DOI] [PubMed] [Google Scholar]
- Carvalho A. B., Clark A. G. Intron size and natural selection. Nature. 1999 Sep 23;401(6751):344–344. doi: 10.1038/43827. [DOI] [PubMed] [Google Scholar]
- Castillo-Davis Cristian I., Mekhedov Sergei L., Hartl Daniel L., Koonin Eugene V., Kondrashov Fyodor A. Selection for short introns in highly expressed genes. Nat Genet. 2002 Jul 22;31(4):415–418. doi: 10.1038/ng940. [DOI] [PubMed] [Google Scholar]
- Chai J. H., Locke D. P., Ohta T., Greally J. M., Nicholls R. D. Retrotransposed genes such as Frat3 in the mouse Chromosome 7C Prader-Willi syndrome region acquire the imprinted status of their insertion site. Mamm Genome. 2001 Nov;12(11):813–821. doi: 10.1007/s00335-001-2083-1. [DOI] [PubMed] [Google Scholar]
- Deutsch M., Long M. Intron-exon structures of eukaryotic model organisms. Nucleic Acids Res. 1999 Aug 1;27(15):3219–3228. doi: 10.1093/nar/27.15.3219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duret L., Mouchiroud D., Gautier C. Statistical analysis of vertebrate sequences reveals that long genes are scarce in GC-rich isochores. J Mol Evol. 1995 Mar;40(3):308–317. doi: 10.1007/BF00163235. [DOI] [PubMed] [Google Scholar]
- Duret L. Why do genes have introns? Recombination might add a new piece to the puzzle. Trends Genet. 2001 Apr;17(4):172–175. doi: 10.1016/s0168-9525(01)02236-3. [DOI] [PubMed] [Google Scholar]
- Greally John M. Short interspersed transposable elements (SINEs) are excluded from imprinted regions in the human genome. Proc Natl Acad Sci U S A. 2001 Dec 26;99(1):327–332. doi: 10.1073/pnas.012539199. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holmes Rebecca, Williamson Christine, Peters Jo, Denny Paul, Wells Christine, RIKEN GER Group. GSL Members A comprehensive transcript map of the mouse Gnas imprinted complex. Genome Res. 2003 Jun;13(6B):1410–1415. doi: 10.1101/gr.955503. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hurst L. D., Brunton C. F., Smith N. G. Small introns tend to occur in GC-rich regions in some but not all vertebrates. Trends Genet. 1999 Nov;15(11):437–439. doi: 10.1016/s0168-9525(99)01832-6. [DOI] [PubMed] [Google Scholar]
- Hurst L. D., McVean G., Moore T. Imprinted genes have few and small introns. Nat Genet. 1996 Mar;12(3):234–237. doi: 10.1038/ng0396-234. [DOI] [PubMed] [Google Scholar]
- John R. M., Surani M. A. Imprinted genes and regulation of gene expression by epigenetic inheritance. Curr Opin Cell Biol. 1996 Jun;8(3):348–353. doi: 10.1016/s0955-0674(96)80008-1. [DOI] [PubMed] [Google Scholar]
- Kalscheuer V. M., Mariman E. C., Schepens M. T., Rehder H., Ropers H. H. The insulin-like growth factor type-2 receptor gene is imprinted in the mouse but not in humans. Nat Genet. 1993 Sep;5(1):74–78. doi: 10.1038/ng0993-74. [DOI] [PubMed] [Google Scholar]
- Kong Augustine, Gudbjartsson Daniel F., Sainz Jesus, Jonsdottir Gudrun M., Gudjonsson Sigurjon A., Richardsson Bjorgvin, Sigurdardottir Sigrun, Barnard John, Hallbeck Bjorn, Masson Gisli. A high-resolution recombination map of the human genome. Nat Genet. 2002 Jun 10;31(3):241–247. doi: 10.1038/ng917. [DOI] [PubMed] [Google Scholar]
- Lercher Martin J., Hurst Laurence D. Imprinted chromosomal regions of the human genome have unusually high recombination rates. Genetics. 2003 Nov;165(3):1629–1632. doi: 10.1093/genetics/165.3.1629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu Jie, Erlichman Beth, Weinstein Lee S. The stimulatory G protein alpha-subunit Gs alpha is imprinted in human thyroid glands: implications for thyroid function in pseudohypoparathyroidism types 1A and 1B. J Clin Endocrinol Metab. 2003 Sep;88(9):4336–4341. doi: 10.1210/jc.2003-030393. [DOI] [PubMed] [Google Scholar]
- Lynch Michael. Intron evolution as a population-genetic process. Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6118–6123. doi: 10.1073/pnas.092595699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore T., Haig D. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet. 1991 Feb;7(2):45–49. doi: 10.1016/0168-9525(91)90230-N. [DOI] [PubMed] [Google Scholar]
- Morison I. M., Paton C. J., Cleverley S. D. The imprinted gene and parent-of-origin effect database. Nucleic Acids Res. 2001 Jan 1;29(1):275–276. doi: 10.1093/nar/29.1.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nabetani A., Hatada I., Morisaki H., Oshimura M., Mukai T. Mouse U2af1-rs1 is a neomorphic imprinted gene. Mol Cell Biol. 1997 Feb;17(2):789–798. doi: 10.1128/mcb.17.2.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Okazaki Y., Furuno M., Kasukawa T., Adachi J., Bono H., Kondo S., Nikaido I., Osato N., Saito R., Suzuki H. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature. 2002 Dec 5;420(6915):563–573. doi: 10.1038/nature01266. [DOI] [PubMed] [Google Scholar]
- Okutsu T., Kuroiwa Y., Kagitani F., Kai M., Aisaka K., Tsutsumi O., Kaneko Y., Yokomori K., Surani M. A., Kohda T. Expression and imprinting status of human PEG8/IGF2AS, a paternally expressed antisense transcript from the IGF2 locus, in Wilms' tumors. J Biochem. 2000 Mar;127(3):475–483. doi: 10.1093/oxfordjournals.jbchem.a022630. [DOI] [PubMed] [Google Scholar]
- Pruitt K. D., Maglott D. R. RefSeq and LocusLink: NCBI gene-centered resources. Nucleic Acids Res. 2001 Jan 1;29(1):137–140. doi: 10.1093/nar/29.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pàldi A., Gyapay G., Jami J. Imprinted chromosomal regions of the human genome display sex-specific meiotic recombination frequencies. Curr Biol. 1995 Sep 1;5(9):1030–1035. doi: 10.1016/s0960-9822(95)00207-7. [DOI] [PubMed] [Google Scholar]
- Robinson W. P., Lalande M. Sex-specific meiotic recombination in the Prader--Willi/Angelman syndrome imprinted region. Hum Mol Genet. 1995 May;4(5):801–806. doi: 10.1093/hmg/4.5.801. [DOI] [PubMed] [Google Scholar]
- Rogozin Igor B., Wolf Yuri I., Sorokin Alexander V., Mirkin Boris G., Koonin Eugene V. Remarkable interkingdom conservation of intron positions and massive, lineage-specific intron loss and gain in eukaryotic evolution. Curr Biol. 2003 Sep 2;13(17):1512–1517. doi: 10.1016/s0960-9822(03)00558-x. [DOI] [PubMed] [Google Scholar]
- Williamson Christine M., Skinner Judith A., Kelsey Gavin, Peters Josephine. Alternative non-coding splice variants of Nespas, an imprinted gene antisense to Nesp in the Gnas imprinting cluster. Mamm Genome. 2002 Feb;13(2):74–79. doi: 10.1007/s00335-001-2102-2. [DOI] [PubMed] [Google Scholar]
- Yamasaki K., Hayashida S., Miura K., Masuzaki H., Ishimaru T., Niikawa N., Kishino T. The novel gene, gamma2-COP (COPG2), in the 7q32 imprinted domain escapes genomic imprinting. Genomics. 2000 Sep 15;68(3):330–335. doi: 10.1006/geno.2000.6265. [DOI] [PubMed] [Google Scholar]