Sequence Determinants of Translation Efficiency

Adam John Hockenberry

doi:https://doi.org/10.21985/N23D6V

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Sequence Determinants of Translation Efficiency

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Bacterial gene expression requires numerous steps that are energetically costly and tightly regulated. Following transcription of messenger-RNA, the translation of mRNA into protein is further regulated by a variety of sequence features both within and upstream of coding sequences. Collectively, these features contribute to the control of translation initiation, elongation, and termination rates that modulate protein abundances. Despite the near universality of the genetic code, species specific control sequences can help to impede or facilitate horizontal gene transfer across species boundaries and recombinant gene expression. A better understanding of the identity and effects of features that control protein translation can both enhance genetic engineering efforts and provide insight into the evolutionary pressures that have shaped bacterial genomes. In the following work, I report on several efforts to increase our understanding of the link between mRNA sequences and protein translation rates. I develop several novel metrics to better quantify the effects of translation initiation motifs, as well as synonymous codon usage biases, and find that these metrics can enhance predictions of genome-wide translation rates and protein abundances. In addition to quantifying the extent of the variation that can be explained by existing knowledge, these results provide insight into the constraints that features of translation initiation place onto the evolution of coding sequences and vice-versa. I further apply comparative genomic methods to show how that genome-wide variation in translation initiation and elongation related features are largely governed by the environments and growth strategies of different organisms.

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