Refining the Ambush Hypothesis: Evidence That GC- and AT-Rich Bacteria Employ Different Frameshift Defence Strategies

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2 Citations (Scopus)

Abstract

Stop codons are frequently selected for beyond their regular termination function for error control. The “ambush hypothesis” proposes out-of-frame stop codons (OSCs) terminating frameshifted translations are selected for. Although early indirect evidence was partially supportive, recent evidence suggests OSC frequencies are not exceptional when considering underlying nucleotide content. However, prior null tests fail to control amino acid/codon usages or possible local mutational biases. We therefore return to the issue using bacterial genomes, considering several tests defining and testing against a null. We employ simulation approaches preserving amino acid order but shuffling synonymous codons or preserving codons while shuffling amino acid order. Additionally, we compare codon usage in amino acid pairs, where one codon can but the next, otherwise identical codon, cannot encode an OSC. OSC frequencies exceed expectations typically in AT-rich genomes, the +1 frame and for TGA/TAA but not TAG. With this complex evidence, simply rejecting or accepting the ambush hypothesis is not warranted. We propose a refined post hoc model, whereby AT-rich genomes have more accidental frameshifts, handled by RF2–RF3 complexes (associated with TGA/TAA) and are mostly +1 (or −2) slips. Supporting this, excesses positively correlate with in silico predicted frameshift probabilities. Thus, we propose a more viable framework, whereby genomes broadly adopt one of the two strategies to combat frameshifts: preventing frameshifting (GC-rich) or permitting frameshifts but minimizing impacts when most are caught early (AT-rich). Our refined framework holds promise yet some features, such as the bias of out-of-frame sense codons, remain unexplained.
Original languageEnglish
Pages (from-to)1153-1173
Number of pages21
JournalGenome biology and evolution
Volume10
Issue number4
DOIs
Publication statusPublished - 1 Apr 2018

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Permethrin
refining
codons
Codon
Terminator Codon
stop codon
genome
amino acid
Bacteria
bacterium
bacteria
Amino Acids
amino acids
Genome
Bacterial Genomes
testing
defence
Computer Simulation
translation (genetics)
simulation

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics

Cite this

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title = "Refining the Ambush Hypothesis: Evidence That GC- and AT-Rich Bacteria Employ Different Frameshift Defence Strategies",
abstract = "Stop codons are frequently selected for beyond their regular termination function for error control. The “ambush hypothesis” proposes out-of-frame stop codons (OSCs) terminating frameshifted translations are selected for. Although early indirect evidence was partially supportive, recent evidence suggests OSC frequencies are not exceptional when considering underlying nucleotide content. However, prior null tests fail to control amino acid/codon usages or possible local mutational biases. We therefore return to the issue using bacterial genomes, considering several tests defining and testing against a null. We employ simulation approaches preserving amino acid order but shuffling synonymous codons or preserving codons while shuffling amino acid order. Additionally, we compare codon usage in amino acid pairs, where one codon can but the next, otherwise identical codon, cannot encode an OSC. OSC frequencies exceed expectations typically in AT-rich genomes, the +1 frame and for TGA/TAA but not TAG. With this complex evidence, simply rejecting or accepting the ambush hypothesis is not warranted. We propose a refined post hoc model, whereby AT-rich genomes have more accidental frameshifts, handled by RF2–RF3 complexes (associated with TGA/TAA) and are mostly +1 (or −2) slips. Supporting this, excesses positively correlate with in silico predicted frameshift probabilities. Thus, we propose a more viable framework, whereby genomes broadly adopt one of the two strategies to combat frameshifts: preventing frameshifting (GC-rich) or permitting frameshifts but minimizing impacts when most are caught early (AT-rich). Our refined framework holds promise yet some features, such as the bias of out-of-frame sense codons, remain unexplained.",
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AU - Hurst, Laurence

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N2 - Stop codons are frequently selected for beyond their regular termination function for error control. The “ambush hypothesis” proposes out-of-frame stop codons (OSCs) terminating frameshifted translations are selected for. Although early indirect evidence was partially supportive, recent evidence suggests OSC frequencies are not exceptional when considering underlying nucleotide content. However, prior null tests fail to control amino acid/codon usages or possible local mutational biases. We therefore return to the issue using bacterial genomes, considering several tests defining and testing against a null. We employ simulation approaches preserving amino acid order but shuffling synonymous codons or preserving codons while shuffling amino acid order. Additionally, we compare codon usage in amino acid pairs, where one codon can but the next, otherwise identical codon, cannot encode an OSC. OSC frequencies exceed expectations typically in AT-rich genomes, the +1 frame and for TGA/TAA but not TAG. With this complex evidence, simply rejecting or accepting the ambush hypothesis is not warranted. We propose a refined post hoc model, whereby AT-rich genomes have more accidental frameshifts, handled by RF2–RF3 complexes (associated with TGA/TAA) and are mostly +1 (or −2) slips. Supporting this, excesses positively correlate with in silico predicted frameshift probabilities. Thus, we propose a more viable framework, whereby genomes broadly adopt one of the two strategies to combat frameshifts: preventing frameshifting (GC-rich) or permitting frameshifts but minimizing impacts when most are caught early (AT-rich). Our refined framework holds promise yet some features, such as the bias of out-of-frame sense codons, remain unexplained.

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