Abstract
Resource optimization in protein synthesis is often looked at from the perspective of translation efficiency-the rate at which proteins are synthesized from a single transcript. The higher the rate of protein synthesis, the more efficiently a transcript is translated. However, the production of a ribosome consumes significantly more cellular resources than an mRNA molecule. Therefore, there should be a stronger selection pressure for optimizing ribosome usage than translation efficiency. This paper reports strong evidence of such optimization which becomes more prominent in highly expressed transcripts that consume a significant amount of cellular resources. The ribosome usage is optimized by the biases in codon usage and translation initiation rates. This optimization significantly reduces the ribosome requirement in Saccharomyces cerevisiae. We also find that a low ribosome density on mRNA transcripts helps optimize ribosome utilization. Therefore, protein synthesis occurs in a low ribosome density regime where translation-initiation is the rate-limiting step. Our results suggest that optimizing ribosome usage is one of the major forces shaping evolutionary selection pressure, and thus provide a new perspective to resource optimization in protein synthesis.