An optimal growth law for RNA composition and its partial implementation through ribosomal and tRNA gene locations in bacterial genomes

Hu, Xiao-Pan; Lercher, Martin J.

doi:10.1371/journal.pgen.1009939

Cited by 16 publications

(24 citation statements)

References 69 publications

(157 reference statements)

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“…the four genes for tRNA GUU -Asn) did not have identical growth impacts, corroborating previous work suggesting that copies of the same tRNA contribute differently to translation ( Dittmar et al, 2004 ). These differences could potentially arise due to genomic location – prior work shows that tRNA gene expression is correlated with distance from the origin of replication ( Ardell and Kirsebom, 2005 ; Hu and Lercher, 2021 ). However, we did not find a correlation between the fitness impacts of gene deletion and distance from the origin of replication, across copies of the same tRNA isotype or across all tRNA genes ( Figure 2—figure supplement 3 ).…”

Section: Resultsmentioning

confidence: 99%

The layered costs and benefits of translational redundancy

Raval

Ngan²,

Gallie³

et al. 2023

eLife

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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.

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Section: Resultsmentioning

confidence: 99%

The layered costs and benefits of translational redundancy

Raval

Ngan²,

Gallie³

et al. 2023

eLife

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“…With respect to the relative size of the rRNA and tRNA pools specifically, it has been observed repeatedly that the ratio of ternary complexes (charged tRNAs bound to EF-Tu⋅GTP) to ribosomes increases at decreasing steady-state growth rates [see Scott et al, 2014 and references therein]. The growth-rate-dependence of this ratio was faithfully replicated theoretically by computing the minimal sum of ribosome and ternary complex masses (RNA and protein) that would yield the protein production rates characteristic for each growth rate ( Hu and Lercher, 2021 ). Furthermore, the optimal ratio of ternary complexes to ribosomes at different steady-state growth rates was proposed to be hard-wired into the genome of fast-growing bacteria, arising as a direct consequence of the relative location of rRNA and tRNA genes relative to the origin of replication ( Hu and Lercher, 2021 ).…”

Section: Discussionmentioning

confidence: 97%

“…The growth-rate-dependence of this ratio was faithfully replicated theoretically by computing the minimal sum of ribosome and ternary complex masses (RNA and protein) that would yield the protein production rates characteristic for each growth rate ( Hu and Lercher, 2021 ). Furthermore, the optimal ratio of ternary complexes to ribosomes at different steady-state growth rates was proposed to be hard-wired into the genome of fast-growing bacteria, arising as a direct consequence of the relative location of rRNA and tRNA genes relative to the origin of replication ( Hu and Lercher, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Escherichia coli protein synthesis is limited by mRNA availability rather than ribosomal capacity during phosphate starvation

2022

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Protein synthesis is the most energetically costly process in the cell. Consequently, it is a tightly regulated process, and regulation of the resources allocated to the protein synthesis machinery is at the heart of bacterial growth optimization theory. However, the molecular mechanisms that result in dynamic downregulation of protein synthesis in response to nutrient starvation are not well described. Here, we first quantify the Escherichia coli response to phosphate starvation at the level of accumulation rates for protein, RNA and DNA. Escherichia coli maintains a low level of protein synthesis for hours after the removal of phosphate while the RNA contents decrease, primarily as a consequence of ribosomal RNA degradation combined with a reduced RNA synthesis rate. To understand the molecular basis for the low protein synthesis rate of phosphate-starved cells, template mRNA for translation was overproduced in the form of a highly induced long-lived mRNA. Remarkably, starved cells increased the rate of protein synthesis and reduced the rate of ribosomal RNA degradation upon mRNA induction. These observations suggest that protein synthesis in phosphate-starved cells is primarily limited by the availability of template, and does not operate at the maximum capacity of the ribosomes. We suggest that mRNA limitation is an adaptive response to phosphate starvation that prevents the deleterious consequences of overcommitting resources to protein synthesis. Moreover, our results support the model that degradation of ribosomal RNA occurs as a consequence of the availability of idle ribosomal subunits.

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“…It is unclear, however, if these genes contain other useful information, such as information about the optimal growth environment for a given species. Previous studies found that ribosomal genes contain some information about a given organism's optimal growth temperature [13][14][15][16][17][18][19][20][21][22][23] . For instance, thermophilic ribosomal proteins were found to have a higher content of arginine, isoleucine, proline, and tyrosine, and a decreased content of serine and threonine.…”

Section: Introductionmentioning

confidence: 99%

“…However, this correlation was not consistent across species to serve as an accurate predictor of an organism's optimal growth temperature 13,14 . A more promising approach was established by studying the correlation between the optimal growth temperature and the G+C content in rRNA [15][16][17][18][19][20][21][22][23] . For example, an almost linear correlation was observed in 143 microbial genera, where the rRNA G+C content gradually increased from about 45% G+C in psychrophilic bacteria to about 55% G+C in thermophilic bacteria 15 .…”

Section: Introductionmentioning

confidence: 99%

Ribosomes as molecular thermometers: metal-binding sites in ribosomal proteins are robust indicators of bacterial adaptation to heat and cold

Elzen

Helena-Bueno

Brown

et al. 2022

Preprint

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Ribosomal genes are widely used as molecular clocks to infer the evolutionary relatedness of species. It is unclear, however, whether these genes can also serve as molecular thermometers to precisely estimate an organisms optimal growth temperature. Previously, some estimations were made using the average nucleotide content in ribosomal RNA, but the universal application of this approach was prevented by numerous outliers. Here, seeking to bypass this problem, we asked whether ribosomal genes contain additional markers of thermal adaptations, aside from their nucleotide composition. To answer this, we analyzed site-specific variations in sequences of ribosomal proteins from 2,021 bacteria with known optimal growth conditions. We found that ribosomal proteins comprise a few mutational hotspots-residues that vary in a temperature-dependent manner and distinguish heat- and cold-adapted bacteria. Most of these residues coordinate metal ions that support protein folding at high temperatures. Using these residues, we then showed that the upper and lower limits of an organisms optimal growth temperatures can be estimated using just 0.001% of the genome sequence or just two amino residues in the cellular proteome. This finding illustrates that laboratory-independent estimation of optimal growth temperatures can be simplified if we abandon the traditional use of rRNA and protein sequences to assess their content and instead focus on those few residues that are most critical for protein structure. This finding may simplify the analysis of unculturable and extinct species by helping bypass the need for laborious, costly, and at times impossible laboratory experiments.

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An optimal growth law for RNA composition and its partial implementation through ribosomal and tRNA gene locations in bacterial genomes

Cited by 16 publications

References 69 publications

The layered costs and benefits of translational redundancy

The layered costs and benefits of translational redundancy

Escherichia coli protein synthesis is limited by mRNA availability rather than ribosomal capacity during phosphate starvation

Ribosomes as molecular thermometers: metal-binding sites in ribosomal proteins are robust indicators of bacterial adaptation to heat and cold

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