PT  - JOURNAL ARTICLE
AU  - Arkin, Adam Paul
AU  - Cambray, Guillaume
TI  - Massive Phenotypic Measurements Reveal Complex Physiological Consequences of Differential Translation Efficacies
AID  - 10.1101/209098
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 209098
4099  - http://biorxiv.org/content/early/2017/10/25/209098.short
4100  - http://biorxiv.org/content/early/2017/10/25/209098.full
AB  - Control of protein biosynthesis is at the heart of resource allocation and cell adaptation to fluctuating environments. One gene’s translation often occurs at the expense of another’s, resulting in global energetic and fitness trade-offs during differential expression of various functions. Patterns of ribosome utilization—as controlled by initiation, elongation and release rates—are central to this balance. To disentangle their respective determinants and physiological impacts, we complemented measurements of protein production with highly parallelized quantifications of transcripts’ abundance and decay, ribosome loading and cellular growth rate for 244,000 precisely designed sequence variants of an otherwise standard reporter. We find highly constrained, non-monotonic relationships between measured phenotypes. We show that fitness defects derive either from protein overproduction, with efficient translation initiation and heavy ribosome flows; or from unproductive ribosome sequestration by highly structured, slowly initiated and overly stabilized transcripts. These observations demonstrate physiological impacts of key sequence features in natural and designed transcripts.