Dataset Information

Selection for tandem stop codons in ciliate species with reassigned stop codons.

ABSTRACT: The failure of mRNA translation machinery to recognize a stop codon as a termination signal and subsequent translation of the 3' untranslated region (UTR) is referred to as stop codon readthrough, the frequency of which is related to the length, composition, and structure of mRNA sequences downstream of end-of-gene stop codons. Secondary in-frame stop codons within a few positions downstream of the primary stop codons, so-called tandem stop codons (TSCs), serve as backup termination signals, which limit the effects of readthrough: polypeptide product degradation, mislocalization, and aggregation. In this study, ciliate species with UAA and UAG stop codons reassigned to code for glutamine are found to possess statistical excesses of TSCs at the beginning of their 3' UTRs. The overrepresentation of TSCs in these species is greater than that observed in standard code organisms. Though the overall numbers of TSCs are lower in most species with alternative stop codons because they use fewer than three unique stop codons, the relatively great overrepresentation of TSCs in alternative-code ciliate species suggests that there exist stronger selective pressures to maintain TSCs in these organisms compared to standard code organisms.

SUBMITTER: Fleming I

PROVIDER: S-EPMC6879139 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Selection for tandem stop codons in ciliate species with reassigned stop codons.

Fleming Ira I Cavalcanti Andre R O ARO

PloS one 20191126 11

The failure of mRNA translation machinery to recognize a stop codon as a termination signal and subsequent translation of the 3' untranslated region (UTR) is referred to as stop codon readthrough, the frequency of which is related to the length, composition, and structure of mRNA sequences downstream of end-of-gene stop codons. Secondary in-frame stop codons within a few positions downstream of the primary stop codons, so-called tandem stop codons (TSCs), serve as backup termination signals, whi ...[more]

PMID: 31770405

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Project description:BackgroundOut-of-frame stop codons (OSCs) occur naturally in coding sequences of all organisms, providing a mechanism of early termination of translation in incorrect reading frame so that the metabolic cost associated with frameshift events can be reduced. Given such a functional significance, we expect statistically overrepresented OSCs in coding sequences as a result of a widespread selection. Accordingly, we examined available prokaryotic genomes to look for evidence of this selection.ResultsThe complete genome sequences of 990 prokaryotes were obtained from NCBI GenBank. We found that low G+C content coding sequences contain significantly more OSCs and G+C content at specific codon positions were the principal determinants of OSC usage bias in the different reading frames. To investigate if there is overrepresentation of OSCs, we modeled the trinucleotide and hexanucleotide biases of the coding sequences using Markov models, and calculated the expected OSC frequencies for each organism using a Monte Carlo approach. More than 93% of 342 phylogenetically representative prokaryotic genomes contain excess OSCs. Interestingly the degree of OSC overrepresentation correlates positively with G+C content, which may represent a compensatory mechanism for the negative correlation of OSC frequency with G+C content. We extended the analysis using additional compositional bias models and showed that lower-order bias like codon usage and dipeptide bias could not explain the OSC overrepresentation. The degree of OSC overrepresentation was found to correlate negatively with the optimal growth temperature of the organism after correcting for the G+C% and AT skew of the coding sequence.ConclusionsThe present study uses approaches with statistical rigor to show that OSC overrepresentation is a widespread phenomenon among prokaryotes. Our results support the hypothesis that OSCs carry functional significance and have been selected in the course of genome evolution to act against unintended frameshift occurrences. Some results also hint that OSC overrepresentation being a compensatory mechanism to make up for the decrease in OSCs in high G+C organisms, thus revealing the interplay between two different determinants of OSC frequency.

Dataset Information

Selection for tandem stop codons in ciliate species with reassigned stop codons.

Publications

Selection for tandem stop codons in ciliate species with reassigned stop codons.

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