Variation in global codon usage bias among prokaryotic organisms is associated with their lifestyles

Abstract

Background: It is widely acknowledged that synonymous codons are used unevenly among genes in a genome. In organisms under translational selection, genes encoding highly expressed proteins are enriched with specific codons. This phenomenon, termed codon usage bias, is common to many organisms and has been recognized as influencing cellular fitness. This suggests that the global extent of codon usage bias of an organism might be associated with its phenotypic traits.

Results: To test this hypothesis we used a simple measure for assessing the extent of codon bias of an organism, and applied it to hundreds of sequenced prokaryotes. Our analysis revealed a large variability in this measure: there are organisms showing very high degrees of codon usage bias and organisms exhibiting almost no differential use of synonymous codons among different genes. Remarkably, we found that the extent of codon usage bias corresponds to the lifestyle of the organism. Especially, organisms able to live in a wide range of habitats exhibit high extents of codon usage bias, consistent with their need to adapt efficiently to different environments. Pathogenic prokaryotes also demonstrate higher extents of codon usage bias than non-pathogenic prokaryotes, in accord with the multiple environments that many pathogens occupy. Our results show that the previously observed correlation between growth rate and metabolic variability is attributed to their individual associations with codon usage bias.

Conclusions: Our results suggest that the extent of codon usage bias of an organism plays a role in the adaptation of prokaryotes to their environments.

Figure 1

Prokaryotes showing extreme GC content have relatively high CAI_ave values spanning a narrower range. Scatter plot of GC content (x-axis) and CAI_ave (y-axis) of 773 organisms. Here and in all other figures CAI_ave is indicated as 'Average CAI'. CAI: Codon Adaptation Index; GC: genome content.

Figure 2

Wide variation in the extents of codon usage bias among various organisms. (a) Distribution of CAI_ave values among 518 prokaryotes with GC content between 35% and 65%. CAI_ave is indicated as 'Average CAI'. (b) Negative correlation between organisms' CAI_ave values and their coefficients of variation. (c) Distribution of CAI values among the genes of Syntrophothermus lipocalidus (high CAI_ave, indicating low extent of codon usage bias). (d) Distribution of CAI values among the genes of Vibrio vulnificus (low CAI_ave, indicating high extent of codon usage bias). CAI: Codon Adaptation Index; GC: genome content.

Figure 3

Prokaryotes exhibiting different environmental characteristics show different extents of codon usage bias. The 518 prokaryotes were classified according to various properties, and the distributions of CAI_ave values of the different classes were compared. (a) Pathogenic prokaryotes show larger extents of codon usage bias than non-pathogenic prokaryotes. CAI_ave is indicated as 'Average CAI'. (b) Facultative prokaryotes show the largest extent of codon usage bias and anaerobic prokaryotes show the smallest extent. (c) Prokaryotes that live in different salinity environments show a statistically significant difference in CAI_ave values. (d) Thermophilic and hyperthermophilic prokaryotes show a smaller extent of codon usage bias than mesophilic prokaryotes. CAI: Codon Adaptation Index; GC: genome content.

Figure 4

The ability of an organism to live in multiple habitats is the feature most correlated with the extent of codon usage bias. The 518 prokaryotes were divided into two groups - organisms who each live in a specialized environment and organisms who each live in multiple habitats - and the CAI_ave values of the different groups were compared. CAI_ave is indicated as 'Average CAI'. CAI: Codon Adaptation Index; GC: genome content.

Figure 5

No correlation between pairwise evolutionary distances across the phylogenetic tree and difference in CAI_ave values of pairs of organisms. Scatter plot of the difference in CAI_ave values between each pair of two organisms in our data (x-axis) and their phylogenetic distances (y-axis). CAI_ave is indicated as 'Average CAI'. The pairwise distances across the phylogenetic tree were based on the tree generated in [38] and computed as the path length between two organisms through the most recent common ancestor. CAI, Codon Adaptation Index.