{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:30:00Z","timestamp":1791055800069,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"19","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: In this article we build a model of the CpG dinucleotide substitution rate and use it to challenge the claim that, that rate underwent a sudden mammalian-specific increase approximately 90 million years ago. The evidence supporting this hypothesis comes from the application of a model of neutral substitution rates able to account for elevated CpG dinucleotide substitution rates. With the initial goal of improving that model's accuracy, we introduced a modification enabling us to account for boundary effects arising by the truncation of the Markov field, as well as improving the optimization procedure required for estimating the substitution rates.<\/jats:p>\n               <jats:p>Results: When using this modified method to reproduce the supporting analysis, the evidence of the rate shift vanished. Our analysis suggests that the CpG-specific rate has been constant over the relevant time period and that the asserted acceleration of the CpG rate is likely an artifact of the original model.<\/jats:p>\n               <jats:p>Contact: \u00a0peifer@uni-graz.at<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btn391","type":"journal-article","created":{"date-parts":[[2008,7,29]],"date-time":"2008-07-29T00:24:15Z","timestamp":1217291055000},"page":"2157-2164","source":"Crossref","is-referenced-by-count":8,"title":["Is there an acceleration of the <i>CpG<\/i> transition rate during the mammalian radiation?"],"prefix":"10.1093","volume":"24","author":[{"given":"M.","family":"Peifer","sequence":"first","affiliation":[{"name":"1 Institute of Chemistry, Karl-Franzens University Graz, Graz, Austria, 2Department of Computer Science and Systems Analysis and 3Department of Microbiology, Miami University, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. E.","family":"Karro","sequence":"additional","affiliation":[{"name":"1 Institute of Chemistry, Karl-Franzens University Graz, Graz, Austria, 2Department of Computer Science and Systems Analysis and 3Department of Microbiology, Miami University, OH, USA"},{"name":"1 Institute of Chemistry, Karl-Franzens University Graz, Graz, Austria, 2Department of Computer Science and Systems Analysis and 3Department of Microbiology, Miami University, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. H.","family":"von Gr\u00fcnberg","sequence":"additional","affiliation":[{"name":"1 Institute of Chemistry, Karl-Franzens University Graz, Graz, Austria, 2Department of Computer Science and Systems Analysis and 3Department of Microbiology, Miami University, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,7,28]]},"reference":[{"key":"2023020211101336400_B1","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1093\/bioinformatics\/bth105","article-title":"Regional and time-resolved mutation patterns of the human genome","volume":"20","author":"Arndt","year":"2004","journal-title":"Bioinformatics"},{"key":"2023020211101336400_B2","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1093\/bioinformatics\/bti376","article-title":"Identification and measurement of neighbor-dependent nucleotide substitution processes","volume":"21","author":"Arndt","year":"2005","journal-title":"Bioinformatics"},{"key":"2023020211101336400_B3","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1093\/molbev\/msg204","article-title":"Distinct changes of genomic biases in nucleotide substitution at the time of mammalian radiation","volume":"20","author":"Arndt","year":"2003","journal-title":"Mol. Biol. Evol"},{"key":"2023020211101336400_B4","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1089\/10665270360688039","article-title":"DNA sequence evolution with neighbor-dependent mutation","volume":"10","author":"Arndt","year":"2003","journal-title":"J. Comp. Biol"},{"key":"2023020211101336400_B5","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1007\/s00239-004-0222-5","article-title":"Substantial regional variation in substitution rates in the human genome: importance of GC content, gene density, and telomere-specific effects","volume":"60","author":"Arndt","year":"2005","journal-title":"J. Mol. Evol"},{"key":"2023020211101336400_B6","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/BF00162968","article-title":"The influence of nearest neighbors on the rate and pattern of spontaneous point mutations","volume":"34","author":"Blake","year":"1992","journal-title":"J. Mol. Evol"},{"key":"2023020211101336400_B7","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1073\/pnas.91.9.3799","article-title":"Pervasive CpG suppression in animal mitrochondrial genomes","volume":"91","author":"Cardon","year":"1994","journal-title":"Proc. Natl Acad. Sci USA"},{"key":"2023020211101336400_B8","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/BF00286715","article-title":"Cytosine methylation and the fate of CpG dinucleotides in vertebrate genomes","volume":"83","author":"Cooper","year":"1989","journal-title":"Hum. Genet"},{"key":"2023020211101336400_B9","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/274775a0","article-title":"Molecular basis of base substitution hotspots in Escherichia coli","volume":"274","author":"Coulondre","year":"1978","journal-title":"Nature"},{"key":"2023020211101336400_B10","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511802843","volume-title":"Bootstrap methods and their application.","author":"Davison","year":"1997"},{"key":"2023020211101336400_B11","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1093\/molbev\/msi109","article-title":"A genomic region evolving toward different GC contents in humans and chimpanzees indicates a recent and regionally limited shift in the mutation pattern","volume":"22","author":"Ebersberger","year":"2005","journal-title":"Mol. Biol. Evol"},{"key":"2023020211101336400_B12","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/BF01116426","article-title":"DNA cytosine methylation and heat-induced deamination","volume":"6","author":"Ehrlich","year":"1986","journal-title":"Biosci. Rep"},{"key":"2023020211101336400_B13","doi-asserted-by":"crossref","DOI":"10.1007\/b137845","volume-title":"Statistical Methods in Bioinformatics: An Introduction.","author":"Ewens","year":"2005"},{"key":"2023020211101336400_B14","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1093\/oxfordjournals.molbev.a026420","article-title":"Cytosine deamination plays a primary role in the evolutiuon of mammalian isochores","volume":"17","author":"Fryxell","year":"2000","journal-title":"Mol. Biol. Evol"},{"key":"2023020211101336400_B15","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1101\/gr.3895005","article-title":"The scale of mutational variation in the murid genome","volume":"15","author":"Gaffney","year":"2005","journal-title":"Genome Res"},{"key":"2023020211101336400_B16","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2307\/2532163","article-title":"Two guidelines for bootstrap hypothesis testing","volume":"47","author":"Hall","year":"1991","journal-title":"Biometrics"},{"key":"2023020211101336400_B17","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1101\/gr.844103","article-title":"Covariation in frequencies of substitution, deletion, transposition, and recombination during eutherian evolution","volume":"13","author":"Hardison,R","year":"2003","journal-title":"Genome Res"},{"key":"2023020211101336400_B18","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1007\/BF02101694","article-title":"Dating of the human-ape splitting by a molecular clock of mitochondrial DNA","volume":"22","author":"Hasegawa","year":"1985","journal-title":"J. Mol. Evol"},{"key":"2023020211101336400_B19","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0168-9525(03)00080-5","article-title":"The methyl-CpG binding domain and evolving role of DNA methylation in animals","volume":"19","author":"Hendrich","year":"2003","journal-title":"Trend Genet"},{"key":"2023020211101336400_B20","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/0022-2836(94)90009-4","article-title":"Wide variations in neighbor-dependent substitution rates","volume":"236","author":"Hess","year":"1994","journal-title":"J. Mol. Biol"},{"key":"2023020211101336400_B21","doi-asserted-by":"crossref","first-page":"13994","DOI":"10.1073\/pnas.0404142101","article-title":"Baysian Markov chain monte carlo sequence analysis reveals varying neutral substitution patterns in mammalian evolution","volume":"101","author":"Hwang","year":"2004","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020211101336400_B22","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0378-1119(97)00475-7","article-title":"Eolutionary changes in CpG and methylation levels in the genome of vertebrates","volume":"205","author":"Jabbari","year":"1997","journal-title":"Gene"},{"key":"2023020211101336400_B23","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/B978-1-4832-3211-9.50009-7","article-title":"Evolution of protein molecules","volume-title":"Mannalian Protein Metabolism.","author":"Jukes","year":"1969"},{"key":"2023020211101336400_B24","doi-asserted-by":"crossref","first-page":"10227","DOI":"10.1073\/pnas.94.19.10227","article-title":"Compositional differences within and between eukaryotic genomes","volume":"94","author":"Karlin","year":"1997","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020211101336400_B25","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/molbev\/msm261","article-title":"Exponential decay of GC content detected by strand-symmetric substitution rates influences the evolution of isochore structure","volume":"25","author":"Karro","year":"2008","journal-title":"Mol. Biol. Evol"},{"key":"2023020211101336400_B26","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The human genome browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res"},{"key":"2023020211101336400_B27","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1371\/journal.pgen.0020163","article-title":"Heterogeneous genomic molecular clocks in primates","volume":"2","author":"Kim","year":"2006","journal-title":"PLoS Genet"},{"key":"2023020211101336400_B28","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1101\/gr.8.12.1233","article-title":"Model of molecular evolution and phylogeny","volume":"8","author":"Lio","year":"1998","journal-title":"Genome Res"},{"key":"2023020211101336400_B29","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1093\/oxfordjournals.molbev.a026156","article-title":"Evolution of DNA base composition under no-strand-bias conditions when the substitution rates are not constant","volume":"16","author":"Lobry","year":"1999","journal-title":"Mol. Biol. Evol"},{"key":"2023020211101336400_B30","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1093\/bioinformatics\/bth901","article-title":"A nucleotide substitution model with nearest-neighbour interactions","volume":"20","author":"Lunter","year":"2004","journal-title":"Bioinformatics"},{"key":"2023020211101336400_B31","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1093\/molbev\/msh070","article-title":"Recombination drives the evolution of GC-content in the human genome","volume":"21","author":"Meunier","year":"2004","journal-title":"Mol. Biol. Evol"},{"key":"2023020211101336400_B32","doi-asserted-by":"crossref","first-page":"5471","DOI":"10.1073\/pnas.0408986102","article-title":"Homology-dependent methylation in primate repetitive DNA","volume":"102","author":"Meunier","year":"2005","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020211101336400_B33","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/bimj.200310112","article-title":"On studentising and blocklength selection for the bootstrap on time series","volume":"47","author":"Peifer","year":"2005","journal-title":"Biometr. J"},{"key":"2023020211101336400_B34","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1126\/science.6254144","article-title":"DNA methylation and gene function","volume":"210","author":"Razin","year":"1980","journal-title":"Science"},{"key":"2023020211101336400_B35","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1214\/aos\/1176344136","article-title":"Estimating the dimension of a model","volume":"6","author":"Schwarz","year":"1978","journal-title":"Ann. Stat"},{"key":"2023020211101336400_B36","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1093\/molbev\/msh039","article-title":"Phylogenetic estimation of context-dependent substitution rates by maximum likelihood","volume":"21","author":"Siepel","year":"2004","journal-title":"Mol. Biol. Evol"},{"key":"2023020211101336400_B37","author":"Smit","year":"1996"},{"key":"2023020211101336400_B38","doi-asserted-by":"crossref","first-page":"17021","DOI":"10.1073\/pnas.0407270101","article-title":"Genomic data support the hominoid slowdown and an early oligocene estimate for the hoinoid-cercopithecoid divergence","volume":"101","author":"Steiper","year":"2004","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020211101336400_B39","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/BF00163236","article-title":"Intrastrand parity rules of DNA base composition and usage biases of synonymous codons","volume":"40","author":"Sueoka","year":"1995","journal-title":"J. Mol. Evol"},{"key":"2023020211101336400_B40","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1128\/MCB.17.3.1469","article-title":"Methylation of genomes and genes at the boundary of invertebrate-vertebrate boundary","volume":"17","author":"Tweedie","year":"1997","journal-title":"Mol. Cell. Biol"},{"key":"2023020211101336400_B41","doi-asserted-by":"crossref","first-page":"R76","DOI":"10.1186\/gb-2008-9-4-r76","article-title":"Human-macaque comparisons illuminate variation in neutral substitution rates","volume":"9","author":"Tyekucheva","year":"2008","journal-title":"Genome Biol"},{"key":"2023020211101336400_B42","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/nature01262","article-title":"Initial sequencing and comparative analysis of the mouse genome","volume":"420","author":"Waterston","year":"2002","journal-title":"Nature"},{"key":"2023020211101336400_B43","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1093\/molbev\/msk008","article-title":"Strong regional biases in nucleotide substitution in the chicken genome","volume":"23","author":"Webster","year":"2006","journal-title":"Mol. Biol. Evol"},{"key":"2023020211101336400_B44","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1007\/978-3-0348-9118-9_23","article-title":"The repair of 5-methylcytosine deamination damage","volume-title":"DNA Methylation: Molecular Biology and Biological Significance.","author":"Wiebauer","year":"1993"},{"key":"2023020211101336400_B45","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1093\/oxfordjournals.molbev.a004043","article-title":"Slow molecular clocks in old world monkeys, apes and humans","volume":"19","author":"Yi","year":"2002","journal-title":"Mol. Biol. Evol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/19\/2157\/49050235\/bioinformatics_24_19_2157.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/19\/2157\/49050235\/bioinformatics_24_19_2157.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T13:32:33Z","timestamp":1675344753000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/24\/19\/2157\/246115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7,28]]},"references-count":45,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2008,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btn391","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2008,10,1]]},"published":{"date-parts":[[2008,7,28]]}}}