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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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Related in: MedlinePlus

The relationship between codon usage and protein function in lambda phage.The figure shows the aqua (CAI, as in Figure 3) and orange (BCAI, as in Figure 5) randomization tests overlaid with information about protein function: genes classified as structural are shown with a white background and all other genes with a grey background. The histograms indicate a clear relationship between the structural classification of a gene and its significance under the aqua and orange tests: structural genes typically have elevated quantiles in the aqua test, whereas other genes typically have depressed quantiles. In other words, structural genes exhibit elevated CAI values when controlling for their amino acid sequence, compared to codon usage in the genome as a whole. Moreover, as the orange histograms indicate, this pattern is not caused by variation in GC3 content: the structural genes exhibit elevated BCAI values after controlling for both their amino acid sequence and their GC3 sequence.
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pcbi-1000001-g009: The relationship between codon usage and protein function in lambda phage.The figure shows the aqua (CAI, as in Figure 3) and orange (BCAI, as in Figure 5) randomization tests overlaid with information about protein function: genes classified as structural are shown with a white background and all other genes with a grey background. The histograms indicate a clear relationship between the structural classification of a gene and its significance under the aqua and orange tests: structural genes typically have elevated quantiles in the aqua test, whereas other genes typically have depressed quantiles. In other words, structural genes exhibit elevated CAI values when controlling for their amino acid sequence, compared to codon usage in the genome as a whole. Moreover, as the orange histograms indicate, this pattern is not caused by variation in GC3 content: the structural genes exhibit elevated BCAI values after controlling for both their amino acid sequence and their GC3 sequence.

Mentions: In the case of lambda phage, Figure 9 shows the results of the aqua CAI and orange BCAI randomization tests, with the structural genes highlighted. The plot reveals a striking pattern: the vast majority of the structural proteins lie on the left half of the genome, exactly in the region where genes have elevated CAI values. In order to quantify this association we performed ANOVAs. Before regressing structural annotations against codon usage, we first removed the non-informative genes – i.e. genes whose codon usage are influenced by their amino acid content, as indicated by a failure to pass the aqua CAI test.


Genome landscapes and bacteriophage codon usage.

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

The relationship between codon usage and protein function in lambda phage.The figure shows the aqua (CAI, as in Figure 3) and orange (BCAI, as in Figure 5) randomization tests overlaid with information about protein function: genes classified as structural are shown with a white background and all other genes with a grey background. The histograms indicate a clear relationship between the structural classification of a gene and its significance under the aqua and orange tests: structural genes typically have elevated quantiles in the aqua test, whereas other genes typically have depressed quantiles. In other words, structural genes exhibit elevated CAI values when controlling for their amino acid sequence, compared to codon usage in the genome as a whole. Moreover, as the orange histograms indicate, this pattern is not caused by variation in GC3 content: the structural genes exhibit elevated BCAI values after controlling for both their amino acid sequence and their GC3 sequence.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1000001-g009: The relationship between codon usage and protein function in lambda phage.The figure shows the aqua (CAI, as in Figure 3) and orange (BCAI, as in Figure 5) randomization tests overlaid with information about protein function: genes classified as structural are shown with a white background and all other genes with a grey background. The histograms indicate a clear relationship between the structural classification of a gene and its significance under the aqua and orange tests: structural genes typically have elevated quantiles in the aqua test, whereas other genes typically have depressed quantiles. In other words, structural genes exhibit elevated CAI values when controlling for their amino acid sequence, compared to codon usage in the genome as a whole. Moreover, as the orange histograms indicate, this pattern is not caused by variation in GC3 content: the structural genes exhibit elevated BCAI values after controlling for both their amino acid sequence and their GC3 sequence.
Mentions: In the case of lambda phage, Figure 9 shows the results of the aqua CAI and orange BCAI randomization tests, with the structural genes highlighted. The plot reveals a striking pattern: the vast majority of the structural proteins lie on the left half of the genome, exactly in the region where genes have elevated CAI values. In order to quantify this association we performed ANOVAs. Before regressing structural annotations against codon usage, we first removed the non-informative genes – i.e. genes whose codon usage are influenced by their amino acid content, as indicated by a failure to pass the aqua CAI test.

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
Related in: MedlinePlus