Abstract

AbstractUnderstanding of the mechanism of DNA mutation process is critical for studying the functional consequences of genetic variation in clinical medicine (eg. drug response) as well as other complex traits (eg. gene expression and cause of common diseases). During the last several decades, many probabilistic models of DNA nucleotide substitution have been proposed for studying this process. A common feature of these mutation models is that they assume the nucleotides evolve independently at each site. In other words, they are sequence context-independent models. However, based on various biochemical studies, it is now recognized that the DNA mutation process resulting in substitutions in both coding and non-coding regions may depend on sequence context. We proposed here a more realistic sequence context-dependent mutation model, which could contribute to the better understanding of the DNA mutation spectrum in genomes.We also showed its application to protein evolution by separating the mutation bias and selection bias in amino acid substitutions.

Highlights

  • Formation of pyrimidine dimers Misincorporation of nucleotides during translesion synthesis DNA polymerase-lesion interactions Methylation C and deamination of methylcytosine in vertebrates

  • Quantify a DNA mutation model that accounts for sequence context-dependency of mutations, i.e effects of immediate neighbors on a mutation

  • Can we find a less complicated model for the 96 classes of mutations in the form of abc->adc, where a,b,c,d are nucleotides and b≠d?

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Summary

Introduction

Of Microbiology & Molecular Genetics The University of Vermont, Burlington, VT 05405 Quantify a DNA mutation model that accounts for sequence context-dependency of mutations, i.e effects of immediate neighbors on a mutation Can we find a less complicated model (with less parameters) for the 96 classes of mutations in the form of abc->adc, where a,b,c,d are nucleotides and b≠d?

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Conclusion

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