scholarly journals Role of Premature Stop Codons in Bacterial Evolution

2008 ◽  
Vol 190 (20) ◽  
pp. 6718-6725 ◽  
Author(s):  
Tit-Yee Wong ◽  
Sanjit Fernandes ◽  
Naby Sankhon ◽  
Patrick P. Leong ◽  
Jimmy Kuo ◽  
...  
Keyword(s):  
Deinococcus Radiodurans ◽  
Stop Codon ◽  
Bacterial Species ◽  
Gc Content ◽  
Limited Range ◽  
Bacterial Evolution ◽  
Stop Codons ◽  
Patterns Of Use ◽  
Frequency Of Use ◽  
Gc Contents

ABSTRACT When the stop codons TGA, TAA, and TAG are found in the second and third reading frames of a protein-encoding gene, they are considered premature stop codons (PSC). Deinococcus radiodurans disproportionately favored TGA more than the other two triplets as a PSC. The TGA triplet was also found more often in noncoding regions and as a stop codon, though the bias was less pronounced. We investigated this phenomenon in 72 bacterial species with widely differing chromosomal GC contents. Although TGA and TAG were compositionally similar, we found a great variation in use of TGA but a very limited range of use of TAG. The frequency of use of TGA in the gene sequences generally increased with the GC content of the chromosome, while the frequency of use of TAG, like that of TAA, was inversely proportional to the GC content of the chromosome. The patterns of use of TAA, TGA and TAG as real stop codons were less biased and less influenced by the GC content of the chromosome. Bacteria with higher chromosomal GC contents often contained fewer PSC trimers in their genes. Phylogenetically related bacteria often exhibited similar PSC ratios. In addition, metabolically versatile bacteria have significantly fewer PSC trimers in their genes. The bias toward TGA but against TAG as a PSC could not be explained either by the preferential usage of specific codons or by the GC contents of individual chromosomes. We proposed that the quantity and the quality of the PSC in the genome might be important in bacterial evolution.

scholarly journals Stop codon recoding is widespread in diverse phage lineages and has the potential to regulate translation of late stage and lytic genes

2021 ◽  
Author(s):  
Adair L Borges ◽  
Yue Clare Lou ◽  
Rohan Sachdeva ◽  
Basem Al-Shayeb ◽  
Alexander L. Jaffe ◽  
...  
Keyword(s):  
Genetic Code ◽  
Late Stage ◽  
Stop Codon ◽  
Gc Content ◽  
Evolutionary Path ◽  
Stop Codons ◽  
Genetic Codes ◽  
Standard Code ◽  
And Control ◽  
Lytic Genes

The genetic code is a highly conserved feature of life. However, some alternative genetic codes use reassigned stop codons to code for amino acids. Here, we survey stop codon recoding across bacteriophages (phages) in human and animal gut microbiomes. We find that stop codon recoding has evolved in diverse clades of phages predicted to infect hosts that use the standard code. We provide evidence for an evolutionary path towards recoding involving reduction in the frequency of TGA and TAG stop codons due to low GC content, followed by acquisition of suppressor tRNAs and the emergence of recoded stop codons in structural and lysis genes. In analyses of two distinct lineages of recoded virulent phages, we find that lysis-related genes are uniquely biased towards use of recoded stop codons. This convergence supports the inference that stop codon recoding is a strategy to regulate the expression of late stage genes and control lysis timing. Interestingly, we identified prophages with recoded stop codons integrated into genomes of bacteria that use standard code, and hypothesize that recoding may control the lytic-lysogenic switch. Alternative coding has evolved many times, often in closely related lineages, indicating that genetic code is plastic in bacteriophages and adaptive recoding can occur over very short evolutionary timescales.

scholarly journals Comprehensive Analysis of Stop Codon Usage in Bacteria and Its Correlation with Release Factor Abundance

2014 ◽  
Vol 289 (44) ◽  
pp. 30334-30342 ◽  
Author(s):  
Gürkan Korkmaz ◽  
Mikael Holm ◽  
Tobias Wiens ◽  
Suparna Sanyal
Keyword(s):  
Codon Usage ◽  
Stop Codon ◽  
Gc Content ◽  
Comprehensive Analysis ◽  
Expression Level ◽  
Release Factor ◽  
Relative Level ◽  
Stop Codons ◽  
Release Factors ◽  
Highly Expressed Genes

We present a comprehensive analysis of stop codon usage in bacteria by analyzing over eight million coding sequences of 4684 bacterial sequences. Using a newly developed program called “stop codon counter,” the frequencies of the three classical stop codons TAA, TAG, and TGA were analyzed, and a publicly available stop codon database was built. Our analysis shows that with increasing genomic GC content the frequency of the TAA codon decreases and that of the TGA codon increases in a reciprocal manner. Interestingly, the release factor 1-specific codon TAG maintains a more or less uniform frequency (∼20%) irrespective of the GC content. The low abundance of TAG is also valid with respect to expression level of the genes ending with different stop codons. In contrast, the highly expressed genes predominantly end with TAA, ensuring termination with either of the two release factors. Using three model bacteria with different stop codon usage (Escherichia coli, Mycobacterium smegmatis, and Bacillus subtilis), we show that the frequency of TAG and TGA codons correlates well with the relative steady state amount of mRNA and protein for release factors RF1 and RF2 during exponential growth. Furthermore, using available microarray data for gene expression, we show that in both fast growing and contrasting biofilm formation conditions, the relative level of RF1 is nicely correlated with the expression level of the genes ending with TAG.

‘Stop’ in protein synthesis is modulated with exquisite subtlety by an extended RNA translation signal

2018 ◽  
Vol 46 (6) ◽  
pp. 1615-1625 ◽  
Author(s):  
Warren P. Tate ◽  
Andrew G. Cridge ◽  
Chris M. Brown
Keyword(s):  
Protein Synthesis ◽  
Conformational Changes ◽  
Stop Codon ◽  
Close Contact ◽  
Gc Content ◽  
Universal Genetic Code ◽  
Rna Translation ◽  
Stop Codons ◽  
Release Factors ◽  
Decoding Efficiency

Translational stop codons, UAA, UAG, and UGA, form an integral part of the universal genetic code. They are of significant interest today for their underlying fundamental role in terminating protein synthesis, but also for their potential utilisation for programmed alternative translation events. In diverse organisms, UAA has wide usage, but it is puzzling that the high fidelity UAG is selected against and yet UGA, vulnerable to suppression, is widely used, particularly in those archaeal and bacterial genomes with a high GC content. In canonical protein synthesis, stop codons are interpreted by protein release factors that structurally and functionally mimic decoding tRNAs and occupy the decoding site on the ribosome. The release factors make close contact with the decoding complex through multiple interactions. Correct interactions cause conformational changes resulting in new and enhanced contacts with the ribosome, particularly between specific bases in the mRNA and rRNA. The base following the stop codon (fourth or +4 base) may strongly influence decoding efficiency, facilitating alternative non-canonical events like frameshifting or selenocysteine incorporation. The fourth base is drawn into the decoding site with a compacted stop codon in the eukaryotic termination complex. Surprisingly, mRNA sequences upstream and downstream of this core tetranucleotide signal have a significant influence on the strength of the signal. Since nine bases downstream of the stop codon are within the mRNA channel, their interactions with rRNA, and r-proteins may affect efficiency. With this understanding, it is now possible to design stop signals of desired strength for specific applied purposes.

Ectopic Transcript Analysis Indicates that Allelic Exclusion is an Important Cause of Type I Protein C Deficiency in Patients with Nonsense and Frameshift Mutations in the PROC Gene

1996 ◽  
Vol 75 (06) ◽  
pp. 870-876 ◽  
Author(s):  
José Manuel Soria ◽  
Lutz-Peter Berg ◽  
Jordi Fontcuberta ◽  
Vijay V Kakkar ◽  
Xavier Estivill ◽  
...  
Keyword(s):  
Splice Site ◽  
Protein C ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Allelic Exclusion ◽  
Polymorphism Analysis ◽  
Type I ◽  
Protein C Deficiency ◽  
Nonsense Mutations ◽  
Stop Codons

SummaryNonsense mutations, deletions and splice site mutations are a common cause of type I protein C deficiency. Either directly or indirectly by altering the reading frame, these' lesions generate or may generate premature stop codons and could therefore be expected to result in premature termination of translation. In this study, the possibility that such mutations could instead exert their pathological effects at an earlier stage in the expression pathway, through “allelic exclusion” at the RNA level, was investigated. Protein C (PROC) mRNA was analysed in seven Spanish type I protein C deficient patients heterozygous for two nonsense mutations, a 7bp deletion, a 2bp insertion and three splice site mutations. Ectopic RNA transcripts from patient and control lymphocytes were analysed by RT-PCR and direct sequencing of amplified PROC cDNA fragments. The nonsense mutations and the deletion were absent from the cDNAs indicating that only mRNA derived from the normal allele had been expressed. Similarly for the splice site mutations, only normal PROC cDNAs were obtained. In one case, exclusion of the mutated allele could be confirmed by polymorphism analysis. In contrast to these six mutations, the 2 bp insertion was not associated with loss of mRNA from the mutated allele. In this case, cDNA analysis revealed the absence of 19 bases from the PROC mRNA consistent with the generation and utilization of a cryptic splice site 3’ to the site of mutation, which would result in a frameshift and a premature stop codon. It is concluded that allelic exclusion is a common causative mechanism in those cases of type I protein C deficiency which result from mutations that introduce premature stop codons

scholarly journals Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events

2021 ◽  
Vol 22 (4) ◽  
pp. 1876
Author(s):  
Frida Belinky ◽  
Ishan Ganguly ◽  
Eugenia Poliakov ◽  
Vyacheslav Yurchenko ◽  
Igor B. Rogozin
Keyword(s):  
Stop Codon ◽  
Purifying Selection ◽  
Protein Product ◽  
Intermediate Step ◽  
Protein Coding ◽  
Stop Codons ◽  
Protein Coding Genes ◽  
Synonymous Sites ◽  
Prokaryotic Protein ◽  
Sense Codon

Nonsense mutations turn a coding (sense) codon into an in-frame stop codon that is assumed to result in a truncated protein product. Thus, nonsense substitutions are the hallmark of pseudogenes and are used to identify them. Here we show that in-frame stop codons within bacterial protein-coding genes are widespread. Their evolutionary conservation suggests that many of them are not pseudogenes, since they maintain dN/dS values (ratios of substitution rates at non-synonymous and synonymous sites) significantly lower than 1 (this is a signature of purifying selection in protein-coding regions). We also found that double substitutions in codons—where an intermediate step is a nonsense substitution—show a higher rate of evolution compared to null models, indicating that a stop codon was introduced and then changed back to sense via positive selection. This further supports the notion that nonsense substitutions in bacteria are relatively common and do not necessarily cause pseudogenization. In-frame stop codons may be an important mechanism of regulation: Such codons are likely to cause a substantial decrease of protein expression levels.

scholarly journals Evolution of Nucleotide Composition in the SARS-CoV-2 Lineage: Implications for Vaccine Design

2020 ◽  
Author(s):  
Sankar Subramanian
Keyword(s):  
Base Composition ◽  
Scientific Community ◽  
Significant Positive Correlation ◽  
Gc Content ◽  
Nucleotide Composition ◽  
Reverse Direction ◽  
Novel Coronavirus ◽  
Near Future ◽  
Systematic Reduction ◽  
Gc Contents

The worldwide outbreak of a novel coronavirus, SARS-CoV-2 has caused a pandemic of respiratory disease. Due to this emergency, researchers around the globe have been investigating the evolution of the genome of SARS-CoV-2 in order to design vaccines. Here I examined the evolution of GC content of SARS-CoV-2 by comparing the genomes of the members of the group Betacoronavirus. The results of this investigation revealed a highly significant positive correlation between the GC contents of betacoronaviruses and their divergence from SARS-CoV-2. The betacoronaviruses that are distantly related to SARS-CoV-2 have much higher GC contents than the latter. Conversely, the closely related ones have low GC contents, which are only slightly higher than that of SARS-CoV-2. This suggests a systematic reduction in the GC content in the SARS-CoV-2 lineage over time. The declining trend in this lineage predicts a much-reduced GC content in the coronaviruses that will descend/evolve from SARS-CoV-2 in the future. Due to the three consecutive outbreaks (MERS-CoV, SARS-CoV and SARS-CoV-2) caused by the members of the SARS-CoV-2, the scientific community is emphasizing the need for universal vaccines that are effective across many strains including those, that will inevitably emerge in the near future. The reduction in GC contents implies an increase in the rate of GC→AT mutations than that the mutational changes in the reverse direction. Therefore, understanding the evolution of base composition and mutational patterns of SARS-CoV-2 could be useful in designing broad-spectrum vaccines that could identify and neutralize the present and future strains of this virus.

scholarly journals Draft Genome Sequence of Streptomyces mexicanus Strain Q0842, Isolated from Human Skin

2020 ◽  
Vol 9 (44) ◽  
Author(s):  
Manon Boxberger ◽  
Mariem Ben Khedher ◽  
Anthony Levasseur ◽  
Bernard La Scola
Keyword(s):  
Human Skin ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Bacterial Species ◽  
Draft Genome ◽  
Gc Content ◽  
Draft Genome Sequence ◽  
Swab Sample ◽  
Partial Genome Sequence ◽  
Partial Genome

ABSTRACT In 2003, Streptomyces mexicanus was reported as a novel xylanolytic bacterial species isolated from soil; a partial genome sequence was determined. In 2019, a strain from the same species was isolated from a hand skin swab sample from a healthy French woman. Genome sequencing revealed an 8,011,832-bp sequence with a GC content of 72.5%.

scholarly journals GPRED-GC: a Gene PREDiction model accounting for 5 ′- 3′ GC gradient

2019 ◽  
Vol 20 (S15) ◽  
Author(s):  
Prapaporn Techa-Angkoon ◽  
Kevin L. Childs ◽  
Yanni Sun
Keyword(s):  
Ab Initio ◽  
Gene Annotation ◽  
Gene Prediction ◽  
Source Code ◽  
Gc Content ◽  
Prediction Tools ◽  
Homologous Sequences ◽  
Manual Intervention ◽  
Grass Genomes ◽  
Gc Contents

Abstract Background Gene is a key step in genome annotation. Ab initio gene prediction enables gene annotation of new genomes regardless of availability of homologous sequences. There exist a number of ab initio gene prediction tools and they have been widely used for gene annotation for various species. However, existing tools are not optimized for identifying genes with highly variable GC content. In addition, some genes in grass genomes exhibit a sharp 5 ′- 3′ decreasing GC content gradient, which is not carefully modeled by available gene prediction tools. Thus, there is still room to improve the sensitivity and accuracy for predicting genes with GC gradients. Results In this work, we designed and implemented a new hidden Markov model (HMM)-based ab initio gene prediction tool, which is optimized for finding genes with highly variable GC contents, such as the genes with negative GC gradients in grass genomes. We tested the tool on three datasets from Arabidopsis thaliana and Oryza sativa. The results showed that our tool can identify genes missed by existing tools due to the highly variable GC contents. Conclusions GPRED-GC can effectively predict genes with highly variable GC contents without manual intervention. It provides a useful complementary tool to existing ones such as Augustus for more sensitive gene discovery. The source code is freely available at https://sourceforge.net/projects/gpred-gc/.

scholarly journals Experimental Evolution of Extreme Resistance to Ionizing Radiation inEscherichia coliafter 50 Cycles of Selection

2019 ◽  
Vol 201 (8) ◽  
Author(s):  
Steven T. Bruckbauer ◽  
Joseph D. Trimarco ◽  
Joel Martin ◽  
Brian Bushnell ◽  
Katherine A. Senn ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Repair ◽  
Ionizing Radiation ◽  
Experimental Evolution ◽  
Deinococcus Radiodurans ◽  
Bacterial Species ◽  
Genomic Sequencing ◽  
Novel Mutations ◽  
Content Type ◽  
Resistance To Ionizing Radiation

ABSTRACTIn previous work (D. R. Harris et al., J Bacteriol 191:5240–5252, 2009, https://doi.org/10.1128/JB.00502-09; B. T. Byrne et al., Elife 3:e01322, 2014, https://doi.org/10.7554/eLife.01322), we demonstrated thatEscherichia colicould acquire substantial levels of resistance to ionizing radiation (IR) via directed evolution. Major phenotypic contributions involved adaptation of organic systems for DNA repair. We have now undertaken an extended effort to generateE. colipopulations that are as resistant to IR asDeinococcus radiodurans. After an initial 50 cycles of selection using high-energy electron beam IR, four replicate populations exhibit major increases in IR resistance but have not yet reached IR resistance equivalent toD. radiodurans. Regular deep sequencing reveals complex evolutionary patterns with abundant clonal interference. Prominent IR resistance mechanisms involve novel adaptations to DNA repair systems and alterations in RNA polymerase. Adaptation is highly specialized to resist IR exposure, since isolates from the evolved populations exhibit highly variable patterns of resistance to other forms of DNA damage. Sequenced isolates from the populations possess between 184 and 280 mutations. IR resistance in one isolate, IR9-50-1, is derived largely from four novel mutations affecting DNA and RNA metabolism: RecD A90E, RecN K429Q, and RpoB S72N/RpoC K1172I. Additional mechanisms of IR resistance are evident.IMPORTANCESome bacterial species exhibit astonishing resistance to ionizing radiation, withDeinococcus radioduransbeing the archetype. As natural IR sources rarely exceed mGy levels, the capacity ofDeinococcusto survive 5,000 Gy has been attributed to desiccation resistance. To understand the molecular basis of true extreme IR resistance, we are using experimental evolution to generate strains ofEscherichia coliwith IR resistance levels comparable toDeinococcus. Experimental evolution has previously generated moderate radioresistance for multiple bacterial species. However, these efforts could not take advantage of modern genomic sequencing technologies. In this report, we examine four replicate bacterial populations after 50 selection cycles. Genomic sequencing allows us to follow the genesis of mutations in populations throughout selection. Novel mutations affecting genes encoding DNA repair proteins and RNA polymerase enhance radioresistance. However, more contributors are apparent.

scholarly journals Structural insights into the main S-layer unit of Deinococcus radiodurans reveal a massive protein complex with porin-like features

2020 ◽  
Vol 295 (13) ◽  
pp. 4224-4236 ◽  
Author(s):  
Domenica Farci ◽  
Mehmet Alphan Aksoyoglu ◽  
Stefano Francesco Farci ◽  
Jayesh Arun Bafna ◽  
Igor Bodrenko ◽  
...  
Keyword(s):  
Surface Layer ◽  
Structural Organization ◽  
Deinococcus Radiodurans ◽  
Bacterial Species ◽  
Particle Analysis ◽  
Outer Cell ◽  
Compact Structure ◽  
Ionic Transporters ◽  
Nonionic Detergent ◽  
Pore Forming Proteins

In the extremophile bacterium Deinococcus radiodurans, the outermost surface layer is tightly connected with the rest of the cell wall. This integrated organization provides a compact structure that shields the bacterium against environmental stresses. The fundamental unit of this surface layer (S-layer) is the S-layer deinoxanthin-binding complex (SDBC), which binds the carotenoid deinoxanthin and provides both, thermostability and UV radiation resistance. However, the structural organization of the SDBC awaits elucidation. Here, we report the isolation of the SDBC with a gentle procedure consisting of lysozyme treatment and solubilization with the nonionic detergent n-dodecyl-β-d-maltoside, which preserved both hydrophilic and hydrophobic components of the SDBC and allows the retention of several minor subunits. As observed by low-resolution single-particle analysis, we show that the complex possesses a porin-like structural organization, but is larger than other known porins. We also noted that the main SDBC component, the protein DR_2577, shares regions of similarity with known porins. Moreover, results from electrophysiological assays with membrane-reconstituted SDBC disclosed that it is a nonselective channel that has some peculiar gating properties, but also exhibits behavior typically observed in pore-forming proteins, such as porins and ionic transporters. The functional properties of this system and its porin-like organization provide information critical for understanding ion permeability through the outer cell surface of S-layer–carrying bacterial species.

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