• DOI:10.1093/OXFORDJOURNALS.MOLBEV.A003888
• Corpus ID: 6485399

Deamination as the basis of strand-asymmetric evolution in transcribed Escherichia coli sequences.

@article{Francino2001DeaminationAT,
  title={Deamination as the basis of strand-asymmetric evolution in transcribed Escherichia coli sequences.},
  author={M. Pilar Francino and Howard Ochman},
  journal={Molecular biology and evolution},
  year={2001},
  volume={18 6},
  pages={
          1147-50
        }
}

• M. P. Francino, H. Ochman
• Published 1 June 2001
• Biology
• Molecular biology and evolution

Analyses of sequence evolution in Escherichia coli and Salmonella enterica have revealed that the pattern of nucleotide substitutions in enterobacterial genes is asymmetric. The incidence of C→T transitions is strongly biased toward the nontranscribed strand of DNA, which accumulates such changes at a twoto threefold higher rate than the complementary transcribed strand. We previously proposed that the asymmetric distribution of C→T substitutions was caused by strand-specific biases in the occurrence and repair of DNA damage during transcription (Francino et al. 1996; Francino and Ochman 1997). Two processes render mutations less likely to originate on the transcribed template strand than on its complement: (1) transcription-coupled repair is induced by RNA polymerases stalled at lesions on the template strand (Hanawalt 1995), and (2) cytosine deamination is less frequent on the template strand, which is shielded by the RNA polymerase and the nascent mRNA, than on the more exposed nontranscribed strand (Beletskii and Bhagwat 1996). However, the pattern of nucleotide substitutions in coding regions may reflect not only the underlying mutational process, but also the action of natural selection. Given that the majority of C→T substitutions in bacterial sequences occur at synonymous sites, selection on codon usage could potentially contribute to the generation of the observed asymmetry. To determine whether transcription alone, without the intervention of natural selection on codon usage, produces substitutional asymmetry in bacterial sequences, we analyzed patterns of substitution in two different noncoding regions: a transcribed but untranslated region, and the adjacent nontranscribed sequence. The detection of substitutional bias in the transcribed but untranslated region and the absence of bias in the nontranscribed sequence would confirm that transcription is necessary and sufficient to generate asymmetry, without a requirement for selection on codon usage. Furthermore, an increase in C→T substitutions with transcription would implicate deamination events in the nontranscribed strand as the principal cause of asymmetry, whereas a decrease in G→A substitutions with transcrip-