Stop codons in bacteria are not selectively equivalent

Abstract

BackgroundThe evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Here we study the rate of evolution and frequency distribution of stop codons in bacterial genomes.ResultsWe show that in bacteria stop codons evolve slower than synonymous sites, suggesting the action of weak negative selection. However, the frequency of stop codons relative to genomic nucleotide content indicated that this selection regime is not straightforward. The frequency of TAA and TGA stop codons is GC-content dependent, with TAA decreasing and TGA increasing with GC-content, while TAG frequency is independent of GC-content. Applying a formal, analytical model to these data we found that the relationship between stop codon frequencies and nucleotide content cannot be explained by mutational biases or selection on nucleotide content. However, with weak nucleotide content-dependent selection on TAG, -0.5 < Nes < 1.5, the model fits all of the data and recapitulates the relationship between TAG and nucleotide content. For biologically plausible rates of mutations we show that, in bacteria, TAG stop codon is universally associated with lower fitness, with TAA being the optimal for G-content < 16% while for G-content > 16% TGA has a higher fitness than TAG.ConclusionsOur data indicate that TAG codon is universally suboptimal in the bacterial lineage, such that TAA is likely to be the preferred stop codon for low GC content while the TGA is the preferred stop codon for high GC content. The optimization of stop codon usage may therefore be useful in genome engineering or gene expression optimization applications.ReviewersThis article was reviewed by Michail Gelfand, Arcady Mushegian and Shamil Sunyaev. For the full reviews, please go to the Reviewers’ Comments section.

Genomic analysis of methanogenic archaea reveals a shift towards energy conservation

“…parvum contains two copies of the formylmethanofuran dehydrogenase complex, one clustered with the Eha energy conserving hydrogenase and one clustered with the heterodisulfide reductase (HdrABC/MvhD) complex. We propose that the two complexes are specific to different ferredoxins, helping to separate the electron pool utilized for anabolism from that utilized to replenish methanogenesis intermediates as previously proposed [ 49 ]. The Eha-mediated electron transfer results in no net energy gain through methanogenesis, but replenishes intermediates lost to leaky electron bifurcation or biosynthesis and anabolism.…”

Concurrent origins of the genetic code and the homochirality of life, and the origin and evolution of biodiversity. Part II: Technical appendix

“…The recruitment order for the three stop codons are #15 UGA , #25 U AG , #31 U AA (Fig 1A, 2B), which results in the different variations of the stop codon usages. Along the evolution direction as the declining GC content, the usage of the first stop codon UGA decreases; the usage of the second stop codon U AG remains almost constantly; the usage of the third stop codon U AA increases (Figure 1 in [18]). The observations of the variations of stop codon usages can be simulated (to compare Fig S2b3 with Figure 1 in [18]) according to the recruitment order of the codon pairs (Fig 2B, S2b1) and the variation range of the stop codon usages.…”

“…Along the evolution direction as the declining GC content, the usage of the first stop codon UGA decreases; the usage of the second stop codon U AG remains almost constantly; the usage of the third stop codon U AA increases (Figure 1 in [18]). The observations of the variations of stop codon usages can be simulated (to compare Fig S2b3 with Figure 1 in [18]) according to the recruitment order of the codon pairs (Fig 2B, S2b1) and the variation range of the stop codon usages. Especially, the detailed features in observation can be simulated that the usage of UGA jump downwards greatly; U AA , upwards greatly, around half GC content (to compare Fig S2b3 with Figure 1 in [18]).…”

“…The observations of the variations of stop codon usages can be simulated (to compare Fig S2b3 with Figure 1 in [18]) according to the recruitment order of the codon pairs (Fig 2B, S2b1) and the variation range of the stop codon usages. Especially, the detailed features in observation can be simulated that the usage of UGA jump downwards greatly; U AA , upwards greatly, around half GC content (to compare Fig S2b3 with Figure 1 in [18]).…”

Concurrent origins of the genetic code and the homochirality of life, and the origin and evolution of biodiversity. Part I: Observations and explanations

“…Non-standard codons also obey pair connections and route dualities, most of which appear in the last route Route 3 ( Fig 1A). [18] for the latter). The recruitment order of codons in the literatures [19] generally agrees with the recruitment order of codons in the roadmap.…”