Resource optimization in protein synthesis*

Resource optimization in protein synthesis is often understood through the lens of translation efficiency, which is the rate of protein synthesis from a single transcript. The greater the rate of protein synthesis, the more resource-efficient the translation of that transcript. Nonetheless, it's important to recognize that the production of ribosomes consumes a substantially larger portion of cellular resources compared to mRNA molecules. Consequently, there is a compelling argument for a more pronounced selection pressure aimed at optimizing ribosome utilization over translation efficiency. Our research presents strong evidence of this optimization, particularly in the context of highly expressed transcripts that place a substantial demand on cellular resources. This ribosome optimization is achieved through biases in codon usage and translation-initiation rates, leading to a substantial reduction in ribosome requirements within the Saccharomyces cerevisiae organism. Additionally, we observe that maintaining a low ribosome density on mRNA transcripts plays a crucial role in optimizing ribosome utilization. Consequently, protein synthesis predominantly occurs within a low ribosome density environment where translation-initiation serves as the rate-limiting step. These findings propose that the optimization of ribosome utilization stands as a significant driving force influencing evolutionary selection pressures. As a result, this research offers a fresh perspective on the resource optimization aspect of protein synthesis.