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Detection of Rare Mutations in CtDNA Using Next Generation Sequencing
Published on: August 24, 2017
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Influence of Electron-Holes on DNA Sequence-Specific Mutation Rates
Martha Y Suárez-Villagrán1,2, Ricardo B R Azevedo3, John H Miller1,2
1Department of Physics, University of Houston, Houston.
Genome Biology and Evolution
|April 5, 2018
Summary
Electron holes, mobile positive charges, correlate with mutation rates across genomes. This suggests hole-enhanced mechanisms significantly influence molecular evolution and sequence-specific mutation patterns.
Area of Science:
- Genetics
- Molecular Biology
- Evolutionary Biology
Background:
- Mutation rate biases impact molecular evolution, causing variations in genomic regions.
- Sequence-specific mutation rates are influenced by various genomic factors.
Purpose of the Study:
- To explore the electron-hole mechanism as a driver of sequence-specific mutation rates.
- To investigate the correlation between electron-hole localization probabilities and observed mutation rates.
Main Methods:
- Computed electron-hole probabilities across different genomic sequences, including bacterial triplets, human mtDNA, and noncoding human DNA.
- Analyzed correlations between computed hole probabilities and mutation/substitution rates from experimental data.
- Compared hole probability correlations with known factors like CpG methylation.
Main Results:
- Significant correlations found between electron-hole probabilities and mutation rates in bacterial triplets.
- Identified correlations between hole probabilities and context-specific mutation/substitution rates in human genomic regions.
- Observed that peaks in hole probability align with mutational hotspots, even in CpG-methylation-poor mtDNA.
Conclusions:
- Electron-hole localization is a significant factor influencing sequence-specific mutation rates.
- Hole-enhanced mechanisms, like oxidation-stabilized tautomerization and deamination, contribute to molecular evolution.
- This mechanism offers a potential explanation for mutation rate variations across the genome.
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