Evolution of phage with chemically ambiguous proteomes

Bacher, Jamie M.; Bull, James J.; Ellington, Andrew D.

doi:10.1186/1471-2148-3-24

Cited by 40 publications

(22 citation statements)

References 54 publications

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“…Remodeling protease cleavage site specificity might establish a genetic trap that is triggered by recombination events that scrambled different polyprotein processing networks (35,36). Experimental phage evolution suggests an alternative approach (37,38). Compensatory mutations occur when fitness loss caused by one mutation is remedied by its epistatic interactions with a second mutation in a different genome location.…”

Section: Discussionmentioning

confidence: 99%

Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: Engineering a recombination-resistant genome

Yount

Roberts

Lindesmith

et al. 2006

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

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Live virus vaccines provide significant protection against many detrimental human and animal diseases, but reversion to virulence by mutation and recombination has reduced appeal. Using severe acute respiratory syndrome coronavirus as a model, we engineered a different transcription regulatory circuit and isolated recombinant viruses. The transcription network allowed for efficient expression of the viral transcripts and proteins, and the recombinant viruses replicated to WT levels. Recombinant genomes were then constructed that contained mixtures of the WT and mutant regulatory circuits, reflecting recombinant viruses that might occur in nature. Although viable viruses could readily be isolated from WT and recombinant genomes containing homogeneous transcription circuits, chimeras that contained mixed regulatory networks were invariantly lethal, because viable chimeric viruses were not isolated. Mechanistically, mixed regulatory circuits promoted inefficient subgenomic transcription from inappropriate start sites, resulting in truncated ORFs and effectively minimize viral structural protein expression. Engineering regulatory transcription circuits of intercommunicating alleles successfully introduces genetic traps into a viral genome that are lethal in RNA recombinant progeny viruses.regulation ͉ systems biology ͉ vaccine design L ive virus vaccines represent a crucial intervention strategy that has been documented to improve the overall health of populations. Concerns regarding reversion to virulence by mutation and recombination, coupled with the associated challenges in developing these vaccines commercially, have diminished the appeal of live virus vaccines (1, 2). The dichotomy between the well known protective efficacy and the costs and risks of developing live virus vaccines has been recognized as a Grand Challenge in Global Health by the National Foundation for Infectious Diseases, which has called for new methods to prevent reversion or recombination repair.Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged suddenly and spread worldwide in 2003, causing Ϸ800 deaths (3). Zoonotic SARS-CoV strains, common in farm animals and bats, dictate a need for continued surveillance and the development of efficacious vaccines (4, 5). SARS-CoV is a tractable system for innovative live virus vaccine design because the pathogen is highly virulent and replicates efficiently in animal models, and a robust reverse genetic system is available. Importantly, CoVs undergo RNA recombination events at high frequency, and recombination-mediated vaccine failures in animals are a problem (6).SARS-CoV contains a positive, single-stranded, Ϸ29,700-nt RNA genome bound by the nucleocapsid protein (N) and an envelope containing the S, ORF3a, E, and M structural proteins. The SARS-CoV genome contains nine ORFs, and ORF1 encodes the viral replicase proteins that are required for subgenomic and genome-length RNA synthesis (7). Downstream of ORF1 and interspaced among the structural genes are the unique SARS-CoV group-specif...

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Section: Discussionmentioning

confidence: 99%

Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: Engineering a recombination-resistant genome

Yount

Roberts

Lindesmith

et al. 2006

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

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“…56 Similar experiments were attempted by Bacher and Ellington some years later (vide infra) but so far without success. 57,58 In 1988, Bronskill and Wong demonstrated that (4-F)Trp could not only be used in 19 F NMR analysis but also facilitates the identification of the contribution of chromophores, like Tyr or Phe, to the spectroscopic features of a protein as (4-F)Trp itself is a non-fluorescent Trp analog. 59 In addition, fluorinated Trp analogs have in general been commonly used to perform spectroscopic and unfolding studies (vide infra and e.g.…”

Section: Biological Incorporation Of Fluorinated Amino Acids Into Pepmentioning

confidence: 99%

Organic fluorine as a polypeptide building element: in vivo expression of fluorinated peptides, proteins and proteomes

Merkel

Budiša

2012

Org. Biomol. Chem.

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“…Other models have been put forward to explain the presence of tRNAs among phage genomes, e.g., models where the presence of tRNAs allows the phage to be resistant to anticodon nucleases in the host (Kaufmann 2000;Blanga-Kanfi et al 2006), the use of alternative genetic codes (see, for example, Bacher et al 2003), or a better integration of lysogenic phages inside the host chromosome (Canchaya et al 2004). The first two hypotheses are based on very few observations, and it is still unclear whether they are indeed strategies to evade host response and whether they are frequently found in nature.…”

Section: Causes For the Presence Of Trnas In Phagesmentioning

confidence: 99%

Causes for the intriguing presence of tRNAs in phages

Bailly‐Bechet¹,

Vergassola²,

Rocha³

2007

Genome Res.

325

259

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Phages have highly compact genomes with sizes reflecting their capacity to exploit the host resources. Here, we investigate the reasons for tRNAs being the only translation-associated genes frequently found in phages. We were able to unravel the selective processes shaping the tRNA distribution in phages by analyzing their genomes and those of their hosts. We found ample evidence against tRNAs being selected to facilitate phage integration in the prokaryotic chromosomes. Conversely, there is a significant association between tRNA distribution and codon usage. We support this observation by introducing a master equation model, where tRNAs are randomly gained from their hosts and then lost either neutrally or according to a set of different selection mechanisms. Those tRNAs present in phages tend to correspond to codons that are simultaneously highly used by the phage genes, while rare in the host genome. Accordingly, we propose that a selective recruitment of tRNAs compensates for the compositional differences between the phage and the host genomes. To further understand the importance of these results in phage biology, we analyzed the differences between temperate and virulent phages. Virulent phages contain more tRNAs than temperate ones, higher codon usage biases, and more important compositional differences with respect to the host genome. These differences are thus in perfect agreement with the results of our master equation model and further suggest that tRNA acquisition may contribute to higher virulence. Thus, even though phages use most of the cell's translation machinery, they can complement it with their own genetic information to attain higher fitness. These results suggest that similar selection pressures may act upon other cellular essential genes that are being found in the recently uncovered large viruses.

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Evolution of phage with chemically ambiguous proteomes

Cited by 40 publications

References 54 publications

Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: Engineering a recombination-resistant genome

Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: Engineering a recombination-resistant genome

Organic fluorine as a polypeptide building element: in vivo expression of fluorinated peptides, proteins and proteomes

Causes for the intriguing presence of tRNAs in phages

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