Leucyl-tRNA synthetase editing domain functions as a molecular rheostat to control codon ambiguity in
            <i>Mycoplasma</i>
            pathogens

Li, Li; Palencia, Andrés; Lukk, T.; Li, Zhi; Luthey‐Schulten, Zaida; Cusack, Stephen; Martinis, Susan A.; Boniecki, Michal T.

doi:10.1073/pnas.1218374110

Cited by 15 publications

(12 citation statements)

References 46 publications

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“…It would be readily visible to natural selection even in wild populations of modest size. As mistranslation rates vary in nature even within strains of the same species42 and can vary more broadly than in our experimental strains443, it is tempting to speculate that prevalent mistranslation rates themselves are a product of adaptive evolution4142444546474849.…”

Section: Discussionmentioning

confidence: 87%

Mistranslation can enhance fitness through purging of deleterious mutations

2017

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Phenotypic mutations are amino acid changes caused by mistranslation. How phenotypic mutations affect the adaptive evolution of new protein functions is unknown. Here we evolve the antibiotic resistance protein TEM-1 towards resistance on the antibiotic cefotaxime in an Escherichia coli strain with a high mistranslation rate. TEM-1 populations evolved in such strains endow host cells with a general growth advantage, not only on cefotaxime but also on several other antibiotics that ancestral TEM-1 had been unable to deactivate. High-throughput sequencing of TEM-1 populations shows that this advantage is associated with a lower incidence of weakly deleterious genotypic mutations. Our observations show that mistranslation is not just a source of noise that delays adaptive evolution. It could even facilitate adaptive evolution by exacerbating the effects of deleterious mutations and leading to their more efficient purging. The ubiquity of mistranslation and its effects render mistranslation an important factor in adaptive protein evolution.

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Section: Discussionmentioning

confidence: 87%

Mistranslation can enhance fitness through purging of deleterious mutations

2017

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“…Finally, the idea of first reducing the activity of an enzyme (here, TadA or TilS) by point mutations, before its complete loss later in evolution, is reminiscent of recent work describing the progressive degeneration of aminoacyl-tRNA synthetases in M. mobile and other closely related Mycoplasmas of Group III-Hominis (53,54). In these cases, the degenerated aminoacyl-tRNA synthetases, while still performing the normal aminoacylation function, occasionally misacylate the cognate tRNA with a non-cognate amino acid.…”

Section: Discussionmentioning

confidence: 99%

Life without tRNAArg–adenosine deaminase TadA: evolutionary consequences of decoding the four CGN codons as arginine in Mycoplasmas and other Mollicutes

Yokobori

Kitamura

Grosjean

et al. 2013

Nucleic Acids Research

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In most bacteria, two tRNAs decode the four arginine CGN codons. One tRNA harboring a wobble inosine (tRNAArgICG) reads the CGU, CGC and CGA codons, whereas a second tRNA harboring a wobble cytidine (tRNAArgCCG) reads the remaining CGG codon. The reduced genomes of Mycoplasmas and other Mollicutes lack the gene encoding tRNAArgCCG. This raises the question of how these organisms decode CGG codons. Examination of 36 Mollicute genomes for genes encoding tRNAArg and the TadA enzyme, responsible for wobble inosine formation, suggested an evolutionary scenario where tadA gene mutations first occurred. This allowed the temporary accumulation of non-deaminated tRNAArgACG, capable of reading all CGN codons. This hypothesis was verified in Mycoplasma capricolum, which contains a small fraction of tRNAArgACG with a non-deaminated wobble adenosine. Subsets of Mollicutes continued to evolve by losing both the mutated tRNAArgCCG and tadA, and then acquired a new tRNAArgUCG. This permitted further tRNAArgACG mutations with tRNAArgGCG or its disappearance, leaving a single tRNAArgUCG to decode the four CGN codons. The key point of our model is that the A-to-I deamination activity had to be controlled before the loss of the tadA gene, allowing the stepwise evolution of Mollicutes toward an alternative decoding strategy.

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“…In this respect, it has been found that the Phe‐tRNA synthase of M. mobile has poor editing incorrectly charging Tyr instead of Phe . A detailed sequence comparison of Mycoplasma tRNA synthases with those of other bacteria revealed in many cases deletions or mutations within their editing domains . This is especially true for the Ala‐tRNA snthetase that has a degenerated C‐Ala domain at its C‐terminus (Supporting Information Fig.…”

Section: Resultsmentioning

confidence: 99%

Rescuing discarded spectra: Full comprehensive analysis of a minimal proteome

et al. 2016

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A common problem encountered when performing large-scale MS proteome analysis is the loss of information due to the high percentage of unassigned spectra. To determine the causes behind this loss we have analyzed the proteome of one of the smallest living bacteria that can be grown axenically, Mycoplasma pneumoniae (729 ORFs). The proteome of M. pneumoniae cells, grown in defined media, was analyzed by MS. An initial search with both Mascot and a species-specific NCBInr database with common contaminants (NCBImpn), resulted in around 79% of the acquired spectra not having an assignment. The percentage of non-assigned spectra was reduced to 27% after re-analysis of the data with the PEAKS software, thereby increasing the proteome coverage of M. pneumoniae from the initial 60% to over 76%. Nonetheless, 33,413 spectra with assigned amino acid sequences could not be mapped to any NCBInr database protein sequence. Approximately, 1% of these unassigned peptides corresponded to PTMs and 4% to M. pneumoniae protein variants (deamidation and translation inaccuracies). The most abundant peptide sequence variants (Phe-Tyr and Ala-Ser) could be explained by alterations in the editing capacity of the corresponding tRNA synthases. About another 1% of the peptides not associated to any protein had repetitions of the same aromatic/hydrophobic amino acid at the N-terminus, or had Arg/Lys at the C-terminus. Thus, in a model system, we have maximized the number of assigned spectra to 73% (51,453 out of the 70,040 initial acquired spectra). All MS data have been deposited in the ProteomeXchange with identifier PXD002779 (http://proteomecentral.proteomexchange.org/dataset/PXD002779).

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Leucyl-tRNA synthetase editing domain functions as a molecular rheostat to control codon ambiguity in Mycoplasma pathogens

Cited by 15 publications

References 46 publications

Mistranslation can enhance fitness through purging of deleterious mutations

Mistranslation can enhance fitness through purging of deleterious mutations

Life without tRNAArg–adenosine deaminase TadA: evolutionary consequences of decoding the four CGN codons as arginine in Mycoplasmas and other Mollicutes

Rescuing discarded spectra: Full comprehensive analysis of a minimal proteome

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