The Effect of Tautomeric Constant on the Specificity of Nucleotide Incorporation during DNA Replication: Support for the Rare Tautomer Hypothesis of Substitution Mutagenesis

Harris, Victoria; Smith, Carl R.; Cummins, W. Jon; Hamilton, Alan; Adams, Harry; Dickman, Mark J.; Hornby, D.; Williams, David M.

doi:10.1016/s0022-2836(03)00051-2

Cited by 105 publications

(68 citation statements)

References 52 publications

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“…Our model choice results together with the unimodally distributed Ti/Tv estimates for ALs (and AE loci as well) suggest that these loci largely evolved via a simple mechanism that gives rise to a transition bias (Wakeley 1996). This finding is significant because it provides evidence in support of the long-standing "rare tautomer hypothesis" by Watson and Crick (1953), which holds that spontaneous base substitutions, which are specifically transitions, arise via incorporation of rare base tautomers during DNA replication (Harris et al 2003;Wang et al 2011). …”

Section: Dna Substitution Patterns In Neutral Locisupporting

confidence: 57%

In silico phylogenomics using complete genomes: a case study on the evolution of hominoids

2016

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The increasing availability of complete genome data is facilitating the acquisition of phylogenomic data sets, but the process of obtaining orthologous sequences from other genomes and assembling multiple sequence alignments remains piecemeal and arduous. We designed software that performs these tasks and outputs anonymous loci (AL) or anchored enrichment/ ultraconserved element loci (AE/UCE) data sets in ready-to-analyze formats. We demonstrate our program by applying it to the hominoids. Starting with human, chimpanzee, gorilla, and orangutan genomes, our software generated an exhaustive data set of 292 ALs (∼1 kb each) in ∼3 h. Not only did analyses of our AL data set validate the program by yielding a portrait of hominoid evolution in agreement with previous studies, but the accuracy and precision of our estimated ancestral effective population sizes and speciation times represent improvements. We also used our program with a published set of 512 vertebrate-wide AE "probe" sequences to generate data sets consisting of 171 and 242 independent loci (∼1 kb each) in 11 and 13 min, respectively. The former data set consisted of flanking sequences 500 bp from adjacent AEs, while the latter contained sequences bordering AEs. Although our AE data sets produced the expected hominoid species tree, coalescent-based estimates of ancestral population sizes and speciation times based on these data were considerably lower than estimates from our AL data set and previous studies. Accordingly, we suggest that loci subjected to direct or indirect selection may not be appropriate for coalescent-based methods. Complete in silico approaches, combined with the burgeoning genome databases, will accelerate the pace of phylogenomics.

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Section: Dna Substitution Patterns In Neutral Locisupporting

confidence: 57%

In silico phylogenomics using complete genomes: a case study on the evolution of hominoids

2016

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“…For structural chemists, rare tautomers of DNA bases are of special interest because they exert strong mutational pressures on the genome (Friedberg et al, 2006;Harris et al, 2003;Kwiatkowski & Pullman, 1975). That's why the tautomerism of DNA bases and their biologically active modifications (Kondratyuk et al, 2000;Samijlenko et al, 2001) have been the subject of a great number of theoretical and experimental investigations due to their biochemical significance.…”

Section: Mutagenic Tautomers Of Dna Basesmentioning

confidence: 99%

Elementary Molecular Mechanisms of the Spontaneous Point Mutations in DNA: A Novel Quantum-Chemical Insight into the Classical Understanding

Brovarets’¹,

Kolomiets²,

Hovorun³

2012

Quantum Chemistry - Molecules for Innovations

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“…Therefore, studies of the photochemistry of thymine may provide insight into the nature of UV-induced carcinogenesis and mutagenesis [4]. Another intriguing characteristic of thymine is its ability to undergo keto-enol tautomerization, which may alter its base pairing properties, form mispairs, and eventually lead to point mutations and molecular based diseases [5]. The tautomeric behavior of thymine has been examined both experimentally and theoretically [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

2,4-Dihydroxy and O2 Protonated Tautomers of dThd and Thd Coexist in the Gas Phase: Methylation Alters Protonation Preferences versus dUrd and Urd

Frieler

et al. 2015

J. Am. Soc. Mass Spectrom.

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The Effect of Tautomeric Constant on the Specificity of Nucleotide Incorporation during DNA Replication: Support for the Rare Tautomer Hypothesis of Substitution Mutagenesis

Cited by 105 publications

References 52 publications

In silico phylogenomics using complete genomes: a case study on the evolution of hominoids

In silico phylogenomics using complete genomes: a case study on the evolution of hominoids

Elementary Molecular Mechanisms of the Spontaneous Point Mutations in DNA: A Novel Quantum-Chemical Insight into the Classical Understanding

2,4-Dihydroxy and O2 Protonated Tautomers of dThd and Thd Coexist in the Gas Phase: Methylation Alters Protonation Preferences versus dUrd and Urd

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