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Genome landscapes and bacteriophage codon usage.

Lucks JB, Nelson DR, Kudla GR, Plotkin JB - PLoS Comput. Biol. (2008)

Bottom Line: We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both.We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins.Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.

View Article: PubMed Central - PubMed

Affiliation: FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA.

ABSTRACT
Across all kingdoms of biological life, protein-coding genes exhibit unequal usage of synonymous codons. Although alternative theories abound, translational selection has been accepted as an important mechanism that shapes the patterns of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns of codon usage across 74 diverse bacteriophages that infect E. coli, P. aeruginosa, and L. lactis as their primary host. We use the concept of a "genome landscape," which helps reveal non-trivial, long-range patterns in codon usage across a genome. We develop a series of randomization tests that allow us to interrogate the significance of one aspect of codon usage, such as GC content, while controlling for another aspect, such as adaptation to host-preferred codons. We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both. We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins. Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.

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Snapshots of simulated synonymous mutation in the lambda phage genome.(A) Shows GC3 and (B) shows CAI landscapes. In between successive snapshots (labeled by integers), N synonymous mutations are introduced into the genome and the resulting landscape is shown, where N is the number of codons in the lambda phage genome (see the Genome Landscapes section). These snapshots show that the simulated genome landscapes approach the random  model, indicated by the purple band (see Figure 1). The final CAI landscape (3) lies almost completely within the purple band. Using the lambda phage mutation rate of 7.7×10−8 mutations/bp/replication [57], we can estimate that approximately 107 genome replications would be required to relax within the purple bars.
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pcbi-1000001-g002: Snapshots of simulated synonymous mutation in the lambda phage genome.(A) Shows GC3 and (B) shows CAI landscapes. In between successive snapshots (labeled by integers), N synonymous mutations are introduced into the genome and the resulting landscape is shown, where N is the number of codons in the lambda phage genome (see the Genome Landscapes section). These snapshots show that the simulated genome landscapes approach the random model, indicated by the purple band (see Figure 1). The final CAI landscape (3) lies almost completely within the purple band. Using the lambda phage mutation rate of 7.7×10−8 mutations/bp/replication [57], we can estimate that approximately 107 genome replications would be required to relax within the purple bars.

Mentions: We can also gain intuition about the degree of non-randomness in the GC3 landscape by considering what would happen if the lambda phage genome were to accumulate random synonymous mutations. Figure 2A shows snapshots of the lambda GC3 landscape as we simulate synonymous mutations to the genome. Between each snapshot, N synonymous mutations were introduced by picking a codon at random along the genome, and then choosing a new synonymous codon at random according to the global lambda phage codon distribution. By preserving the global codon distribution in each synonymous variation of the genome, this procedure inherently controls for any mutational bias or other source of global codon usage bias that may be present in the phage genome nucleotide content. The same is true for all randomization tests discussed in this paper. As more mutations are introduced, the GC3 landscape of the synonymously mutated lambda genome approaches the purple band, indicating that the GC3 pattern in the real lambda phage genome is highly non-random.


Genome landscapes and bacteriophage codon usage.

Lucks JB, Nelson DR, Kudla GR, Plotkin JB - PLoS Comput. Biol. (2008)

Snapshots of simulated synonymous mutation in the lambda phage genome.(A) Shows GC3 and (B) shows CAI landscapes. In between successive snapshots (labeled by integers), N synonymous mutations are introduced into the genome and the resulting landscape is shown, where N is the number of codons in the lambda phage genome (see the Genome Landscapes section). These snapshots show that the simulated genome landscapes approach the random  model, indicated by the purple band (see Figure 1). The final CAI landscape (3) lies almost completely within the purple band. Using the lambda phage mutation rate of 7.7×10−8 mutations/bp/replication [57], we can estimate that approximately 107 genome replications would be required to relax within the purple bars.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2266997&req=5

pcbi-1000001-g002: Snapshots of simulated synonymous mutation in the lambda phage genome.(A) Shows GC3 and (B) shows CAI landscapes. In between successive snapshots (labeled by integers), N synonymous mutations are introduced into the genome and the resulting landscape is shown, where N is the number of codons in the lambda phage genome (see the Genome Landscapes section). These snapshots show that the simulated genome landscapes approach the random model, indicated by the purple band (see Figure 1). The final CAI landscape (3) lies almost completely within the purple band. Using the lambda phage mutation rate of 7.7×10−8 mutations/bp/replication [57], we can estimate that approximately 107 genome replications would be required to relax within the purple bars.
Mentions: We can also gain intuition about the degree of non-randomness in the GC3 landscape by considering what would happen if the lambda phage genome were to accumulate random synonymous mutations. Figure 2A shows snapshots of the lambda GC3 landscape as we simulate synonymous mutations to the genome. Between each snapshot, N synonymous mutations were introduced by picking a codon at random along the genome, and then choosing a new synonymous codon at random according to the global lambda phage codon distribution. By preserving the global codon distribution in each synonymous variation of the genome, this procedure inherently controls for any mutational bias or other source of global codon usage bias that may be present in the phage genome nucleotide content. The same is true for all randomization tests discussed in this paper. As more mutations are introduced, the GC3 landscape of the synonymously mutated lambda genome approaches the purple band, indicating that the GC3 pattern in the real lambda phage genome is highly non-random.

Bottom Line: We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both.We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins.Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.

View Article: PubMed Central - PubMed

Affiliation: FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA.

ABSTRACT
Across all kingdoms of biological life, protein-coding genes exhibit unequal usage of synonymous codons. Although alternative theories abound, translational selection has been accepted as an important mechanism that shapes the patterns of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns of codon usage across 74 diverse bacteriophages that infect E. coli, P. aeruginosa, and L. lactis as their primary host. We use the concept of a "genome landscape," which helps reveal non-trivial, long-range patterns in codon usage across a genome. We develop a series of randomization tests that allow us to interrogate the significance of one aspect of codon usage, such as GC content, while controlling for another aspect, such as adaptation to host-preferred codons. We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both. We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins. Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.

Show MeSH