balanced codon usage optimizes eukaryotic translational efficiency平衡的密码子使用优化真核转化效率.pdf

Balanced Codon Usage Optimizes Eukaryotic Translational Efficiency 1 1,2 1¤ 1 1 Wenfeng Qian , Jian-Rong Yang , Nathaniel M. Pearson , Calum Maclean , Jianzhi Zhang * 1 Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan, United States of America, 2 Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China Abstract Cellular efficiency in protein translation is an important fitness determinant in rapidly growing organisms. It is widely believed that synonymous codons are translated with unequal speeds and that translational efficiency is maximized by the exclusive use of rapidly translated codons. Here we estimate the in vivo translational speeds of all sense codons from the budding yeast Saccharomyces cerevisiae. Surprisingly, preferentially used codons are not translated faster than unpreferred ones. We hypothesize that this phenomenon is a result of codon usage in proportion to cognate tRNA concentrations, the optimal strategy in enhancing translational efficiency under tRNA shortage. Our predicted codon–tRNA balance is indeed observed from all model eukaryotes examined, and its impact on translational efficiency is further validated experimentally. Our study reveals a previously unsuspected mechanism by which unequal codon usage increases translational efficiency, demonstrates widespread natural selection for translational efficiency, and offers new strategies to improve synthetic biology. Citation: Qian W, Yang J-R, Pearson NM, Maclean C, Zhang J (2012) Balanced Codon Usage Optimizes Eukaryotic Translational Efficienc