Highlights d A new methodology to detect and quantify most translation errors in proteomes d Most amino acid substitutions result from mis-pairing between codons and anti-codons d Proteins' error rates are reduced at conserved and highly expressed proteins d Translation speed is negatively correlated with error rates
SUMMARY
Gene expression burdens cells by consuming resources and energy. While numerous studies have investigated regulation of expression level, little is known about gene design elements that govern expression costs. Here, we ask how cells minimize production costs while maintaining a given protein expression level and whether there are gene architectures that optimize this process. We measured fitness of ~14,000 E. coli strains, each expressing a reporter gene with a unique 5′ architecture. By comparing cost-effective and ineffective architectures, we found that cost per protein molecule could be minimized by lowering transcription levels, regulating translation speeds, and utilizing amino acids that are cheap to synthesize and that are less hydrophobic. We then examined natural E. coli genes and found that highly expressed genes have evolved more forcefully to minimize costs associated with their expression. Our study thus elucidates gene design elements that improve the economy of protein expression in natural and heterologous systems.
Tracing evolutionary processes that lead to fixation of genomic variation in wild bacterial populations is a prime challenge in molecular evolution. In particular, the relative contribution of Horizontal Gene Transfer (HGT) versus de novo mutations during adaptation to a new environment is poorly understood. To gain a better understanding of the dynamics of HGT and its effect on adaptation, we subjected several populations of competent Bacillus subtilis to a serial dilution evolution on a high salt containing medium, either with or without foreign DNA from diverse pre-adapted or naturally salt tolerant species. Following 504 generations of evolution, all populations improved growth yield on the medium. Sequencing of evolved populations revealed extensive acquisition of foreign DNA from close Bacillus donors but not from more remote donors. HGT occurred in bursts, whereby a single bacterial cell appears to have acquired dozens of fragments at once. In the largest burst, close to 2% of the genome has been replaced by HGT. Acquired segments tend to be clustered in integration "hot spots". Other than HGT, genomes also acquired spontaneous mutations. Many of these mutations occurred within, and seem to alter, the sequence of flagellar proteins. Finally, we show that while some HGT fragments could be neutral, others are adaptive and accelerate evolution.
In our manuscript, we characterized various mechanisms by which bacterial cells express similar levels of proteins in an efficient manner that reduces production costs in terms of energy and building block usage.
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