Discrete Whole Cell Model of Translation Enables Connecting the Genotype to the Phenotype

Whole cell modeling of translation is a fundamental component of synthetic and systems biology. In particular, such a model must incorporate the effect of nucleotide composition of the transcript on translation initiation and elongation, the dynamics and the discrete aspects of the process, the properties of the ribosome and the limited resources of the cell (e.g. a finite ribosome pool, shared by all transcripts).

In this work we present, for the first time, such a complete model that not only allows simulating the translation process at a whole cell scale, but also to predict the effect of mutations at the nucleotide level on translation. We demonstrate how this model enables accurate engineering of genomes and heterologous genes, understanding various aspects related to the dynamics of translation, and understanding the evolution of genomes.