TY - JOUR
T1 - Universally high transcript error rates in bacteria
AU - Li, Weiyi
AU - Lynch, Michael
N1 - Funding Information:
We thank Stephen Simpson, W Kelley Thomas, Samuel F Miller, Jiaqi Zheng, Jie Huang, and James Ford for technical support, and Daniel Kearns and Clay Fuqua for providing B. subtilis NCIB 3610 and A. tumefaciens C58 strains. We also thank Hongan Long, Michelle Marasco, Chi-Chun Chen, Parul Johri, and Jean-Francois Gout for helpful discussions. This work was supported by National Institutes of Health Awards R01-GM036827 and R35-GM122566, and Multidisciplinary University Research Initiative Award W911NF-09-1-0444 and W911NF-14-1-0411 from the US Army Research Office (to ML).
Publisher Copyright:
© Li and Lynch.
PY - 2020/5
Y1 - 2020/5
N2 - Errors can occur at any level during the replication and transcription of genetic information. Genetic mutations derived mainly from replication errors have been extensively studied. However, fundamental details of transcript errors, such as their rate, molecular spectrum, and functional effects, remain largely unknown. To globally identify transcript errors, we applied an adapted rolling-circle sequencing approach to Escherichia coli, Bacillus subtilis, Agrobacterium tumefaciens, and Mesoplasma florum, revealing transcript-error rates 3 to 4 orders of magnitude higher than the corresponding genetic mutation rates. The majority of detected errors would result in amino-acid changes, if translated. With errors identified from 9929 loci, the molecular spectrum and distribution of errors were uncovered in great detail. A GfiA substitution bias was observed in M. florum, which apparently has an error-prone RNA polymerase. Surprisingly, an increased frequency of nonsense errors towards the 30 end of mRNAs was observed, suggesting a Nonsense-Mediated Decay-like quality-control mechanism in prokaryotes.
AB - Errors can occur at any level during the replication and transcription of genetic information. Genetic mutations derived mainly from replication errors have been extensively studied. However, fundamental details of transcript errors, such as their rate, molecular spectrum, and functional effects, remain largely unknown. To globally identify transcript errors, we applied an adapted rolling-circle sequencing approach to Escherichia coli, Bacillus subtilis, Agrobacterium tumefaciens, and Mesoplasma florum, revealing transcript-error rates 3 to 4 orders of magnitude higher than the corresponding genetic mutation rates. The majority of detected errors would result in amino-acid changes, if translated. With errors identified from 9929 loci, the molecular spectrum and distribution of errors were uncovered in great detail. A GfiA substitution bias was observed in M. florum, which apparently has an error-prone RNA polymerase. Surprisingly, an increased frequency of nonsense errors towards the 30 end of mRNAs was observed, suggesting a Nonsense-Mediated Decay-like quality-control mechanism in prokaryotes.
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U2 - 10.7554/eLife.54898
DO - 10.7554/eLife.54898
M3 - Article
C2 - 32469307
AN - SCOPUS:85085676468
SN - 2050-084X
VL - 9
SP - 1
EP - 15
JO - eLife
JF - eLife
M1 - e54898
ER -