An environmental signature for 323 microbial genomes based on codon adaptation indices

Abstract

Background: Codon adaptation indices (CAIs) represent an evolutionary strategy to modulate gene expression and have widely been used to predict potentially highly expressed genes within microbial genomes. Here, we evaluate and compare two very different methods for estimating CAI values, one corresponding to translational codon usage bias and the second obtained mathematically by searching for the most dominant codon bias.

Results: The level of correlation between these two CAI methods is a simple and intuitive measure of the degree of translational bias in an organism, and from this we confirm that fast replicating bacteria are more likely to have a dominant translational codon usage bias than are slow replicating bacteria, and that this translational codon usage bias may be used for prediction of highly expressed genes. By analyzing more than 300 bacterial genomes, as well as five fungal genomes, we show that codon usage preference provides an environmental signature by which it is possible to group bacteria according to their lifestyle, for instance soil bacteria and soil symbionts, spore formers, enteric bacteria, aquatic bacteria, and intercellular and extracellular pathogens.

Conclusion: The results and the approach described here may be used to acquire new knowledge regarding species lifestyle and to elucidate relationships between organisms that are far apart evolutionarily.

Figure 1

Box plot summarizing correlations between tCAI and dCAI for eight major bacterial phyla and fungi. The group 'Other bacteria' comprises a number of minor bacterial phyla (Aquificae, Chloroflexi, Fusobacteria, Planctomycetes, Acidobacteria, and Thermotogae) that could not meaningfully be included in any of the other categories. The box plot illustrates the median correlations of each group as well as upper and lower quartiles. The numbers on the right side of the figure specifies the number of genomes included in each group. dCAI, dominant codon adaptation index; tCAI, translational codon adaptation index.

Figure 2

Two-dimensional cluster analysis of differential codon preferences for tCAI and dCAI. The differences in relative adaptiveness of each codon (w_ij for tCAI minus w_ij for dCAI) for each Genbank entry were clustered into two dimensions, one clustering codons and the other clustering Genbank entries. The clustering was performed as a hierarchical cluster analysis using Euclidian distances and complete linkage. Codons preferred relatively more by dCAI are red, whereas codons preferred relatively more by tCAI are green. Equal preference is indicated by white. (a) Entire dendrogram. The five major regions are indicated and microbial names are replaced by a color bar reflecting each microbe's phylum. (b) Zoom of the third and fourth regions. Weights not considered: start codon 'ATG' and stop codons 'TGA', 'TAG' and 'TAA'. dCAI, dominant codon adaptation index; tCAI, translational codon adaptation index.

Figure 3

Venn diagram evaluating the prediction of highly expressed genes (tCAI and dCAI) by comparison with microarray gene expression data (Expr). The overlap between genes with top 10% tCAI, dCAI, and Expr values are pictured as overlapping circles, in which the number of genes found by either method is given. The organisms are sorted in order of decreasing correlation (rho) between tCAI and dCAI values based on all genes in each organism. For organisms with high correlation (high rho) between tCAI and dCAI values, most genes are predicted as highly expressed by both measures. Moreover, these predictions overlap significantly with genes found to be highly expressed experimentally by microarrays. For organisms with low correlation (low rho) between tCAI and dCAI values, few genes are predicted as highly expressed by both measures. Here, more genes predicted as highly expressed by tCAI are found to be highly expressed by microarrays than for dCAI. dCAI, dominant codon adaptation index; tCAI, translational codon adaptation index.