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Effects of DNA oxidation on the evolution of genomes

By Michael Sheinman, Rutger Hermsen

Posted 15 Jun 2017
bioRxiv DOI: 10.1101/150425

Oxidation of DNA increases its mutation rate, causing otherwise rare G → T transversions during DNA replication. Here we use a comparative genomic approach to assess the importance of DNA oxidation for the evolution of genomic sequences. To do so, we study the mutational spectrum of Gn-tracks on various timescales, ranging from one human generation to the divergence between primates, and compare it to the properties of guanines oxidation known from experimental and computational studies. Our results suggest that, in short Gn tracks (n ≤ 3), oxidation does not dominate the mutagenesis of guanines, except in cancerous tumors, especially in lungs. However, we consistently find that the G → T transversion rate is elevated by an order of magnitude in long Gn tracks (n ≳ 6). In such long Gn-tracks, G → T substitutions in fact dominate the mutational spectrum, suggesting that long Gn tracks are oxidized more frequently and/or repaired less efficiently.

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