Conserved rates and patterns of transcription errors across bacterial growth states and lifestyles

Abstract

Errors that occur during transcription have received much less attention than the mutations that occur in DNA because transcription errors are not heritable and usually result in a very limited number of altered proteins. However, transcription error rates are typically several orders of magnitude higher than the mutation rate. Also, individual transcripts can be translated multiple times, so a single error can have substantial effects on the pool of proteins. Transcription errors can also contribute to cellular noise, thereby influencing cell survival under stressful conditions, such as starvation or antibiotic stress. Implementing a method that captures transcription errors genome-wide, we measured the rates and spectra of transcription errors in Escherichia coli and in endosymbionts for which mutation and/or substitution rates are greatly elevated over those of E. coli. Under all tested conditions, across all species, and even for different categories of RNA sequences (mRNA and rRNAs), there were no significant differences in rates of transcription errors, which ranged from 2.3 × 10−5 per nucleotide in mRNA of the endosymbiont Buchnera aphidicola to 5.2 × 10−5 per nucleotide in rRNA of the endosymbiont Carsonella ruddii. The similarity of transcription error rates in these bacterial endosymbionts to that in E. coli (4.63 × 10−5 per nucleotide) is all the more surprising given that genomic erosion has resulted in the loss of transcription fidelity factors in both Buchnera and Carsonella.

Drift barriers to quality control when genes are expressed at different levels

“…In agreement with drift barrier theory, large-N e E. coli exhibits a local solution-a tendency for transcription errors to have synonymous effects-while small-N e B. aphidicola does not (Traverse and Ochman 2016a). While, as predicted, the global solution of low transcriptional error rates does not obey the naïve drift barrier expectation of being higher in B. aphidicola than in E. coli (Traverse and Ochman 2016a), nor are transcription error rates drastically lower in B. aphidicola as predicted by previous theory on the interplay between global and local solutions (Rajon and Masel 2011;McCandlish and Plotkin 2016).…”

“…While, as predicted, the global solution of low transcriptional error rates does not obey the naïve drift barrier expectation of being higher in B. aphidicola than in E. coli (Traverse and Ochman 2016a), nor are transcription error rates drastically lower in B. aphidicola as predicted by previous theory on the interplay between global and local solutions (Rajon and Masel 2011;McCandlish and Plotkin 2016). This significantly lower rate relative to E. coli is, however, found in intermediate-N e C. elegans.…”

“…The simplest interpretation of the drift barrier would seem to imply that large-N e species show stricter quality control over all biological processes, e.g., higher fidelity in DNA replication, transcription, and translation, than small-N e species, because molecular defects in quality control mechanisms are less effectively purged in the latter (Lynch 2010;Traverse and Ochman 2016a).…”

Enhanced CHO Clone Screening: Application of Targeted Locus Amplification and Next‐Generation Sequencing Technologies for Cell Line Development

“…Such errors are not heritable and usually result in a very limited number of altered proteins. Traverse et al had measured the rates of transcription errors in Escherichia coli and in endosymbionts to range from 2 × 10 −5 to 5 × 10 −5 per base. Gout et al had analyzed the transcriptome of Caenorhabditis elegan and had detected a transcription error rate of 4 × 10 −6 .…”

Transcriptional errors and the drift barrier

“…The CircSeq protocol (8) sequences the same nucleotide fragments several times in tandem, allowing errors in sequencing to be identified by differences among these tandem copies, rather than between the genome and the tandem copies. This procedure produces error rates of less than 10 −6 per base (8), much lower than the transcriptional error rates of 3.4 × 10 −5 to 5.1 × 10 −5 reported by Traverse and Ochman (4). Furthermore, as the quality score cutoff used in their analysis increases, the error rates inferred by Traverse and Ochman decrease and then asymptote.…”