The rate and accuracy of translation hinges upon multiple components - including transfer RNA (tRNA) pools, tRNA modifying enzymes, and rRNA molecules - many of which are redundant in terms of gene copy number or function. It has been hypothesized that the redundancy evolves under selection, driven by its impacts on growth rate. However, we lack empirical measurements of the fitness costs and benefits of redundancy, and we have poor a understanding of how this redundancy is organized across components. We manipulated redundancy in multiple translation components of Escherichia coli by deleting 28 tRNA genes, 3 tRNA modifying systems, and 4 rRNA operons in various combinations. We find that redundancy in tRNA pools is beneficial when nutrients are plentiful and costly under nutrient limitation. This nutrient-dependent cost of redundant tRNA genes stems from upper limits to translation capacity and growth rate, and therefore varies as a function of the maximum growth rate attainable in a given nutrient niche. The loss of redundancy in rRNA genes and tRNA modifying enzymes had similar nutrient-dependent fitness consequences. Importantly, these effects are also contingent upon interactions across translation components, indicating a layered hierarchy from copy number of tRNA and rRNA genes to their expression and downstream processing. Overall, our results indicate both positive and negative selection on redundancy in translation components, depending on a species' evolutionary history with feasts and famines.
Keywords: E. coli; evolutionary biology; fitness costs; rRNA; redundancy; tRNA; tRNA modifying enzyme; translation rate.
Translation is the process by which cellular machines called ribosomes use the information encoded in genes to make proteins . Every organism requires two types of RNA molecules to make new proteins: ribosomal RNAs (rRNAs, which form part of the ribosome) and transfer RNAs (tRNAs, which transport the amino acid molecules that form proteins to the ribosomes). These RNA molecules are coded in the genome, but different organisms have different ‘copy numbers’: some genomes contain just a few copies of each of these genes, while others have thousands. This apparent redundancy – the presence of several copies of the same gene – is puzzling because it is costly to make and maintain DNA and RNA. This leads to an important question: how does redundancy in these important genes (coding for tRNAs and rRNAs) evolve? The answer is key to understanding how one of the most fundamental cellular processes, the making of proteins from DNA, has evolved. A possible reason for organisms to have many copies of the genes required to make proteins is to allow rapid translation, which allows cells to divide faster, and populations of cells to grow more quickly. However, this would likely mean that, when nutrients are scarce, carrying and translating many copies of the same gene would become a burden on the cell. Raval et al. set out to test this idea by measuring the costs and benefits of seemingly redundant translation components. To do this, Raval et al. deleted some of the redundant gene copies in the bacterium Escherichia coli and asked if that changed bacterial growth. The experiments showed that when nutrients were plentiful, cells with more copies of the genes (high redundancy) were better able to use the nutrients and divide rapidly. However, when nutrients were limited, bacteria with extra gene copies divided more slowly, showing that the extra genes are indeed a big burden on the cell. Raval et al. propose that nutrients available in the environment ultimately determine whether redundancy of the translation machinery is a blessing or a curse. This suggests that the redundancy and underlying growth strategies of different organisms are forged by their experiences of feast and famine during their evolutionary past. Importantly, by testing the joint effect of many different molecules involved in translation, Raval et al. uncovered several strategies that may maximize bacterial growth and protein production. Their results could thus be useful for optimizing the synthesis of important products that use growing cells as factories – from beer to insulin – where the rate of growth is critical.
© 2023, Raval et al.