title: Differences in codon bias cannot explain differences in translational power among microbes.
abstract: BACKGROUND
  Translational power is the cellular rate of protein synthesis normalized to the biomass invested in translational machinery. Published data suggest a previously unrecognized pattern: translational power is higher among rapidly growing microbes, and lower among slowly growing microbes. One factor known to affect translational power is biased use of synonymous codons. The correlation within an organism between expression level and degree of codon bias among genes of Escherichia coli and other bacteria capable of rapid growth is commonly attributed to selection for high translational power. Conversely, the absence of such a correlation in some slowly growing microbes has been interpreted as the absence of selection for translational power. Because codon bias caused by translational selection varies between rapidly growing and slowly growing microbes, we investigated whether observed differences in translational power among microbes could be explained entirely by differences in the degree of codon bias. Although the data are not available to estimate the effect of codon bias in other species, we developed an empirically-based mathematical model to compare the translation rate of E. coli to the translation rate of a hypothetical strain which differs from E. coli only by lacking codon bias.
  
  
  RESULTS
  Our reanalysis of data from the scientific literature suggests that translational power can differ by a factor of 5 or more between E. coli and slowly growing microbial species. Using empirical codon-specific in vivo translation rates for 29 codons, and several scenarios for extrapolating from these data to estimates over all codons, we find that codon bias cannot account for more than a doubling of the translation rate in E. coli, even with unrealistic simplifying assumptions that exaggerate the effect of codon bias. With more realistic assumptions, our best estimate is that codon bias accelerates translation in E. coli by no more than 60% in comparison to microbes with very little codon bias.
  
  
  CONCLUSIONS
  While codon bias confers a substantial benefit of faster translation and hence greater translational power, the magnitude of this effect is insufficient to explain observed differences in translational power among bacterial and archaeal species, particularly the differences between slowly growing and rapidly growing species. Hence, large differences in translational power suggest that the translational apparatus itself differs among microbes in ways that influence translational performance.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824, USA. dethlefs@stanford.edu
authors.forename: Les
authors.initials: L
authors.lastname: Dethlefsen
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Schmidt
mesh_terms: D018407:Bacterial Physiological Phenomena; D015982:Bias; D003062:Codon; D019295:Computational Biology / Q000379:methods*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D019766:Genes, Archaeal; D005798:Genes, Bacterial; D008957:Models, Genetic; D015233:Models, Statistical; D014176:Protein Biosynthesis; D012270:Ribosomes / Q000378:metabolism; D012641:Selection, Genetic; D013816:Thermodynamics
chemical_list: D003062:Codon