Role of Premature Stop Codons in Bacterial Evolution

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.

Stop codons in bacteria are not selectively equivalent

“…The relationship between stop codon frequency and G-content, or GC-content as reported previously [14], is one of the most striking and unambiguous patterns in bacterial genome composition (Figure 1). Here, we have developed a simple model that captures all of the major observations of stop codon distribution across bacterial genomes.…”

“…Firstly, translation termination efficiency may be nucleotide context dependent [9-13]. Second, TAG and TGA stop codon frequencies in bacterial genomes with different GC-contents are strikingly different (see Figure 1 in [14]), such that TGA frequency increases with genomic GC-content while TAG is GC-content independent. Here, we study stop codon frequency and evolution in bacterial genomes to gain an understanding of whether or not stop codons are used indiscriminately without any fitness costs.…”

A holin remnant protein encoded by STY1365 is involved in envelope stability of Salmonella enterica serovar Typhi

“…Sequence analysis of STY1365 showed the presence of a premature stop codon (TGA) within its single TM domain, suggesting the disruption of this segment, and consequently this protein will not be inserted within the bacterial membrane. The frequency of use of TGA as a premature stop codon in bacterial genomes increases with the increase in GC content, a classical feature of genomic regions acquired by horizontal transfer (Wong et al , 2008). This is in accordance with the genomic location of STY1365, which is part of a genomic island (GICT18/1) with high GC content compared with whole genome of S .…”

“…In addition, we detected the presence of a protein in the inner membrane of S. Typhi ($17 kDa) consistent with the molecular weight of STY1365 protein product plus FLAG tag, suggesting that STY1365 is fully translated. It has been reported that some phage genes containing TGA premature stop codon can be hopped by ribosomes, allowing protein synthesis (Goldman et al, 2000;Wong et al, 2008;Vakhrusheva et al, 2011).…”

Taking the pseudo out of pseudogenes

“…The 49 Rickettsia genomes available in Ensembl Bacteria (release 22) [32] have small chromosome sizes (range 0.86-1.82 Mb; mean 1.23Mb), low %GC contents (mean 31.7%) and reduced coding capacities (mean 76%). Low %GC contents are important in this context, as alternative-frame premature stop-codons are more prevalent in AT-rich genomes, which are hypothesised to serve as error-correcting sequences to minimise the effect of deleterious frameshift mutations [33]. The genomes of both M. leprae [13] and S. glossinidius [24,34] have coding capacities of only 50%, suggesting there has not been sufficient evolutionary time or selective pressure for non-coding regions to be removed.…”