GC composition of the human genome: in search of isochores
- PMID:15728737
- DOI: 10.1093/molbev/msi115
GC composition of the human genome: in search of isochores
Abstract
The isochore theory, proposed nearly three decades ago, depicts the mammalian genome as a mosaic of long, fairly homogeneous genomic regions that are characterized by their guanine and cytosine (GC) content. The human genome, for instance, was claimed to consist of five distinct isochore families: L1, L2, H1, H2, and H3, with GC contents of <37%, 37%-42%, 42%-47%, 47%-52%, and >52%, respectively. In this paper, we address the question of the validity of the isochore theory through a rigorous sequence-based analysis of the human genome. Toward this end, we adopt a set of six attributes that are generally claimed to characterize isochores and statistically test their veracity against the available draft sequence of the complete human genome. By the selection criteria used in this study: distinctiveness, homogeneity, and minimal length of 300 kb, we identify 1,857 genomic segments that warrant the label "isochore." These putative isochores are nonuniformly scattered throughout the genome and cover about 41% of the human genome. We found that a four-family model of putative isochores is the most parsimonious multi-Gaussian model that can be fitted to the empirical data. These families, however, are GC poor, with mean GC contents of 35%, 38%, 41%, and 48% and do not resemble the five isochore families in the literature. Moreover, due to large overlaps among the families, it is impossible to classify genomic segments into isochore families reliably, according to compositional properties alone. These findings undermine the utility of the isochore theory and seem to indicate that the theory may have reached the limits of its usefulness as a description of genomic compositional structures.
Comment in
- How not to search for isochores: a reply to Cohen et Al.Clay O, Bernardi G.Clay O, et al.Mol Biol Evol. 2005 Dec;22(12):2315-7. doi: 10.1093/molbev/msi231. Epub 2005 Aug 10.Mol Biol Evol. 2005.PMID:16093569
Similar articles
- Isochore patterns and gene distributions in fish genomes.Costantini M, Auletta F, Bernardi G.Costantini M, et al.Genomics. 2007 Sep;90(3):364-71. doi: 10.1016/j.ygeno.2007.05.006. Epub 2007 Jun 21.Genomics. 2007.PMID:17590311
- A computational prediction of isochores based on hidden Markov models.Melodelima C, Guéguen L, Piau D, Gautier C.Melodelima C, et al.Gene. 2006 Dec 30;385:41-9. doi: 10.1016/j.gene.2006.04.032. Epub 2006 Aug 17.Gene. 2006.PMID:17020791
- Isochores and replication time zones: a perfect match.Schmegner C, Hameister H, Vogel W, Assum G.Schmegner C, et al.Cytogenet Genome Res. 2007;116(3):167-72. doi: 10.1159/000098182.Cytogenet Genome Res. 2007.PMID:17317955
- The vertebrate genome: isochores and evolution.Bernardi G.Bernardi G.Mol Biol Evol. 1993 Jan;10(1):186-204. doi: 10.1093/oxfordjournals.molbev.a039994.Mol Biol Evol. 1993.PMID:8450755Review.
- Recombination explains isochores in mammalian genomes.Montoya-Burgos JI, Boursot P, Galtier N.Montoya-Burgos JI, et al.Trends Genet. 2003 Mar;19(3):128-30. doi: 10.1016/S0168-9525(03)00021-0.Trends Genet. 2003.PMID:12615004Review.
Cited by
- Illumina Library Preparation for Sequencing the GC-Rich Fraction of Heterogeneous Genomic DNA.Tilak MK, Botero-Castro F, Galtier N, Nabholz B.Tilak MK, et al.Genome Biol Evol. 2018 Feb 1;10(2):616-622. doi: 10.1093/gbe/evy022.Genome Biol Evol. 2018.PMID:29385572Free PMC article.
- The Anolis Lizard Genome: An Amniote Genome without Isochores?Costantini M, Greif G, Alvarez-Valin F, Bernardi G.Costantini M, et al.Genome Biol Evol. 2016 Apr 13;8(4):1048-55. doi: 10.1093/gbe/evw056.Genome Biol Evol. 2016.PMID:26992416Free PMC article.
- IsoPlotter(+): A Tool for Studying the Compositional Architecture of Genomes.Elhaik E, Graur D.Elhaik E, et al.ISRN Bioinform. 2013 Apr 18;2013:725434. doi: 10.1155/2013/725434. eCollection 2013.ISRN Bioinform. 2013.PMID:25937951Free PMC article.
- Characterization of in vitro and in vivo hypomethylating effects of decitabine in acute myeloid leukemia by a rapid, specific and sensitive LC-MS/MS method.Liu Z, Liu S, Xie Z, Blum W, Perrotti D, Paschka P, Klisovic R, Byrd J, Chan KK, Marcucci G.Liu Z, et al.Nucleic Acids Res. 2007;35(5):e31. doi: 10.1093/nar/gkl1156. Epub 2007 Jan 30.Nucleic Acids Res. 2007.PMID:17264127Free PMC article.
- Remarkable evolutionary conservation of SOX14 orthologues.Popovic J, Stevanovic M.Popovic J, et al.J Genet. 2009 Apr;88(1):15-24. doi: 10.1007/s12041-009-0003-4.J Genet. 2009.PMID:19417540
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous