Dosage constraint of the ribosome-associated molecular chaperone drives the evolution and fates of its duplicates in bacteria.

Gene duplication events happen prevalently during evolution, and the mechanisms governing the loss or retention of duplicated genes are mostly elusive. Our genome scanning analysis revealed that trigger factor (TF), the one and only bacterial ribosome-associated molecular chaperone, is singly copied in virtually every bacterium except for a very few that possess two or more copies. However, even in these exceptions, only one complete TF copy exists, while other homologs lack the N-terminal domain that contains the conserved ribosome binding site (RBS) motif. Consistently, we demonstrated that the overproduction of the N-terminal complete TF proteins is detrimental to the cell, which can be rescued by removing the N-terminal domain. Our findings also indicated that TF overproduction leads to a decrease in protein productivity and profile changes in proteome due to its characteristic ribosome binding and holdase activities. Additionally, these N-terminal deficient TF homologs in bacteria with multiple TF homologs partition the function of TF via subfunctionalization. Our results revealed that TF is subjected to a dosage constraint that originates from its own intrinsic functions, which may drive the evolution and fates of duplicated TFs in bacteria. IMPORTANCE: Gene duplication events presumably occur in