RT Journal Article SR Electronic T1 Macromolecular crowding links ribosomal protein gene dosage to growth rate in Vibrio cholerae JF bioRxiv FD Cold Spring Harbor Laboratory SP 619304 DO 10.1101/619304 A1 Alfonso Soler-Bistué A1 Sebastián Aguilar-Pierlé A1 Marc Garcia-Garcerá A1 Marie-Eve Val A1 Odile Sismeiro A1 Hugo Varet A1 Rodrigo Sieira A1 Evelyne Krin A1 Ole Skovgaard A1 Diego J. Comerci A1 Eduardo P. C. Rocha A1 Didier Mazel YR 2019 UL http://biorxiv.org/content/early/2019/04/25/619304.abstract AB Ribosomal protein (RP) genes locate near the replication origin (oriC) in fast-growing bacteria, which is thought to have been selected as a translation optimization strategy. Relocation of S10-spc-α locus (S10), which codes for most of the RP, to ectopic genomic positions shows that its relative distance to the oriC correlates to a reduction on its dosage, its expression, and bacterial growth rate. Deep-sequencing revealed that S10 relocation altered chromosomal replication dynamics and genome-wide transcription. Such changes increased as a function of oriC-S10 distance. Strikingly, in this work we observed that protein production capacity was independent of S10 position. Since RP constitute a large proportion of cell mass, lower S10 dosage could lead to changes in macromolecular crowding, impacting cell physiology. Accordingly, cytoplasm fluidity was higher in mutants where S10 is most distant from oriC. In hyperosmotic conditions, when crowding differences are minimized, the growth rate and replication dynamics were highly alleviated in these strains. Therefore, on top of its essential function in translation, RP genomic location contributes to sustain optimal macromolecular crowding. This is a novel mechanism coordinating DNA replication with bacterial growth.