Discrete Whole Cell Model for High Resolution Study of Translation Dynamics

Background: Whole cell modelling 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 or a tRNA pool).

Methods: 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 have developed a generalization of the TASEP (Totally Asymmetric Exclusion Process) model to take into account the previously described aspects and the complex relation between them.

Results: We show that our model not only predicts the dynamics of translation more accurately than alternative models, but, more importantly, allows the study of complex cell-related questions (such as heterologous gene expression, extremely important for many bio-technological applications), which are impossible to assess with other models.

Conclusion: 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.