Sequences that direct significant levels of frameshifting are frequent in coding regions of Escherichia coli

Gurvich, Olga L.; Baranov, Pavel V.; Zhou, Jiadong; Hammer, Andrew; Gesteland, Raymond F.; Atkins, John F.

doi:10.1093/emboj/cdg561

Cited by 80 publications

(108 citation statements)

References 57 publications

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“…Potentially deleterious effects of a mononucleotide repeat in coding sequences (CDS) have been pointed out: the mononucleotide repeats in CDS are prone to transcriptional and translational slippage, which leads to functional disruption of the corresponding gene products (Wagner et al 1990;Gurvich et al 2003;Baranov et al 2005); a strong association between mononucleotide repeats and the occurrence of insertion/deletion (indel) during the DNA replication process will elevate the risk of frameshift mutations (Strauss 1999), which might have severe fitness consequences. The list of diseases resulting from changes of unstable repeats continues to grow (Gatchel and Zoghbi 2005 escape from polymerase proofreading or mismatch repair (MMR) systems (Kroutil et al 1996;Tran et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Avoidance of Long Mononucleotide Repeats in Codon Pair Usage

Tan

Gou

et al. 2010

Genetics

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Protein is an essential component for life, and its synthesis is mediated by codons in any organisms on earth. While some codons encode the same amino acid, their usage is often highly biased. There are many factors that can cause the bias, but a potential effect of mononucleotide repeats, which are known to be highly mutable, on codon usage and codon pair preference is largely unknown. In this study we performed a genomic survey on the relationship between mononucleotide repeats and codon pair bias in 53 bacteria, 68 archaea, and 13 eukaryotes. By distinguishing the codon pair bias from the codon usage bias, four general patterns were revealed: strong avoidance of five or six mononucleotide repeats in codon pairs; lower observed/expected (o/e) ratio for codon pairs with C or G repeats (C/G pairs) than that with A or T repeats (A/T pairs); a negative correlation between genomic GC contents and the o/e ratios, particularly for C/G pairs; and avoidance of C/G pairs in highly conserved genes. These results support natural selection against long mononucleotide repeats, which could induce frameshift mutations in coding sequences. The fact that these patterns are found in all kingdoms of life suggests that this is a general phenomenon in living organisms. Thus, long mononucleotide repeats may play an important role in base composition and genetic stability of a gene and gene functions.A MONG the many components of life, protein is most essential because living organisms use proteins not only for body structuring but also for its functioning. After the discovery of the genetic code for protein biosynthesis (Crick et al. 1961), redundancy in the genetic code attracted great attention. Highly biased use of synonymous codons is one of them, and the codon usage bias is common not only among species but also within species (Grosjean and Fiers 1982;Akashi 2001). Previous studies showed that codon usage bias is linked to several factors, such as efficiency and accuracy of translation (Robinson et al. 1984;Bulmer 1991;Akashi 1994;Plotkin et al. 2004), compositional bias (Muto and Osawa 1987;McLean et al. 1998), and genome size or other nonselective forces (Lawrence and Ochman 1998;dos Reis et al. 2004).One additional factor is the sequence environment. It is known that nucleotides surrounding a codon can influence the codon usage preference, called contextdependent codon bias (Yarus and Folley 1985). The context-dependent codon bias affects the efficiency and accuracy of translation (Taniguchi and Weissmann 1978;Irwin et al. 1995) and the suppression of both premature stop codons and missense codons (Bossi and Ruth 1980;Murgola et al. 1984). Reflecting the context-dependent codon bias, a strong codon pair bias is detected in both prokaryotic and eukaryotic genomes (Gutman and Hatfield 1989;Buchan et al. 2006;Tats et al. 2008). It has been suggested that codon pair preference is influenced by all three nucleotides of the ribosomal A-site codon and the third nucleotide of the P-site codon (Buchan et al. 2006). Therefore,...

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Section: Introductionmentioning

confidence: 99%

Avoidance of Long Mononucleotide Repeats in Codon Pair Usage

Tan

Gou

et al. 2010

Genetics

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“…Homopolymeric tracts, particularly stretches of nine or more As or Ts, are prone to enzyme slippage that can alter the tract length compared with the template molecule (1)(2)(3). Long considered ''hotspots'' for mutation, recent studies have begun to clarify the evolutionary and functional implications of these error-prone genomic regions.…”

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confidence: 99%

Endosymbiont gene functions impaired and rescued by polymerase infidelity at poly(A) tracts

Tamaš

Wernegreen

Nystedt

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Among host-dependent bacteria that have evolved by extreme reductive genome evolution, long-term bacterial endosymbionts of insects have the smallest (160 -790 kb) and most A ؉ T-rich (>70%) bacterial genomes known to date. These genomes are riddled with poly(A) tracts, and 5-50% of genes contain tracts of 10 As or more. Here, we demonstrate transcriptional slippage at poly(A) tracts within genes of Buchnera aphidicola associated with aphids and Blochmannia pennsylvanicus associated with ants. Several tracts contain single frameshift deletions; these apparent pseudogenes showed patterns of constraint consistent with purifying selection on the encoded proteins. Transcriptional slippage yielded a heterogeneous population of transcripts with variable numbers of As in the tract. Across several frameshifted genes, including B. aphidicola cell wall biosynthesis genes and a B. pennsylvanicus histidine biosynthesis gene, 12-50% of transcripts contained corrected reading frames that could potentially yield fulllength proteins. In situ immunostaining confirmed the production of the cell wall biosynthetic enzyme UDP-N-acetylmuramyl pentapeptide synthase encoded by the frameshifted murF gene. Simulation studies indicated an overrepresentation of poly(A) tracts in endosymbiont genomes relative to other A ؉ T-rich bacterial genomes. Polymerase infidelity at poly(A) tracts rescues the functionality of genes with frameshift mutations and, conversely, reduces the efficiency of expression for in-frame genes carrying poly(A) regions. These features of homopolymeric tracts could be exploited to manipulate gene expression in small synthetic genomes.homopolymeric tracts ͉ pseudogenes ͉ Blochmannia pennsylvanicus ͉ transcriptional slippage ͉ Buchnera aphidicola

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“…Consequently, one might expect shift-prone sequences to be selected against and therefore underrepresented in coding sequences, especially those of highly expressed genes. Conversely, when shiftprone sequences occur, analysis for their possible utilization in gene expression is merited (25,52). …”

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confidence: 99%

Expression Levels Influence Ribosomal Frameshifting at the Tandem Rare Arginine Codons AGG_AGG and AGA_AGA in Escherichia coli

et al. 2005

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The rare codons AGG and AGA comprise 2% and 4%, respectively, of the arginine codons of Escherichia coli K-12, and their cognate tRNAs are sparse. At tandem occurrences of either rare codon, the paucity of cognate aminoacyl tRNAs for the second codon of the pair facilitates peptidyl-tRNA shifting to the ؉1 frame. However, AGG_AGG and AGA_AGA are not underrepresented and occur 4 and 42 times, respectively, in E. coli genes. Searches for corresponding occurrences in other bacteria provide no strong support for the functional utilization of frameshifting at these sequences. All sequences tested in their native context showed 1.5 to 11% frameshifting when expressed from multicopy plasmids. A cassette with one of these sequences singly integrated into the chromosome in stringent cells gave 0.9% frameshifting in contrast to two-to four-times-higher values obtained from multicopy plasmids in stringent cells and eight-times-higher values in relaxed cells. Thus, ؉1 frameshifting efficiency at AGG_AGG and AGA_AGA is influenced by the mRNA expression level. These tandem rare codons do not occur in highly expressed mRNAs.

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Sequences that direct significant levels of frameshifting are frequent in coding regions of Escherichia coli

Cited by 80 publications

References 57 publications

Avoidance of Long Mononucleotide Repeats in Codon Pair Usage

Avoidance of Long Mononucleotide Repeats in Codon Pair Usage

Endosymbiont gene functions impaired and rescued by polymerase infidelity at poly(A) tracts

Expression Levels Influence Ribosomal Frameshifting at the Tandem Rare Arginine Codons AGG_AGG and AGA_AGA in Escherichia coli

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