Estimation of DNA sequence context-dependent mutation rates using primate genomic sequences.

Estimation of DNA sequence context-dependent mutation rates using primate genomic sequences. Research Abstract Details 

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Estimation of DNA sequence context-dependent mutation rates using primate genomic sequences. Abstract Text:

Wei Zhang,Gerard G Bouffard,Susan S Wallace,Jeffrey P Bond, ,Wei Zhang,Gerard G Bouffard,Susan S Wallace,Jeffrey P Bond, ,Wei Zhang,Gerard G Bouffard,Susan S Wallace,Jeffrey P Bond, ,

It is understood that DNA and amino acid substitution rates are highly sequence context-dependent, e.g., C --> T substitutions in vertebrates may occur much more frequently at CpG sites and that cysteine substitution rates may depend on support of the context for participation in a disulfide bond. Furthermore, many applications rely on quantitative models of nucleotide or amino acid substitution, including phylogenetic inference and identification of amino acid sequence positions involved in functional specificity. We describe quantification of the context dependence of nucleotide substitution rates using baboon, chimpanzee, and human genomic sequence data generated by the NISC Comparative Sequencing Program. Relative mutation rates are reported for the 96 classes of mutations of the form 5' alphabetagamma 3' --> 5' alphadeltagamma 3', where alpha, beta, gamma, and delta are nucleotides and beta not equal delta, based on maximum likelihood calculations. Our results confirm that C --> T substitutions are enhanced at CpG sites compared with other transitions, relatively independent of the identity of the preceding nucleotide. While, as expected, transitions generally occur more frequently than transversions, we find that the most frequent transversions involve the C at CpG sites (CpG transversions) and that their rate is comparable to the rate of transitions at non-CpG sites. A four-class model of the rates of context-dependent evolution of primate DNA sequences, CpG transitions > non-CpG transitions approximately CpG transversions > non-CpG transversions, captures qualitative features of the mutation spectrum. We find that despite qualitative similarity of mutation rates among different genomic regions, there are statistically significant differences.

Estimation of DNA sequence context-dependent mutation rates using primate genomic sequences. Publishing Authors By Initials

W Zhang,GG Bouffard,SS Wallace,JP Bond, ,W Zhang,GG Bouffard,SS Wallace,JP Bond, ,W Zhang,GG Bouffard,SS Wallace,JP Bond, ,

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Estimation of DNA sequence context-dependent mutation rates using primate genomic sequences. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of molecular evolution

VOLUME: 65

Page Numbers: 207-14

Journal Abbreviation: J. Mol. Evol.

ISSN: 0022-2844

DAY: 4

MONTH: 08

YEAR: 2007

Estimation of DNA sequence context-dependent mutation rates using primate genomic sequences. Information

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LANGUAGE: eng

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AFFILIATION: Department of Medicine, University of Chicago, 515 CLSC, Chicago, IL 60637, USA.

Country: Germany

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MEDLINETA: J Mol Evol

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