On 1 September at 14:15 Karl Jürgenstein will defend his doctoral thesis “A context-dependent interplay of translational fidelity and genome stability in Pseudomonas species” for the award of the degree of Doctor of Genetics.
Live broadcast through Zoom Meeting ID: 961 2887 9857 Passcode: 928337
Supervisors:
Professor Maia Kivisaar, University of Tartu
Associate professor Jaanus Remme, University of Tartu
Research fellow Heili llves, University of Tartu
Opponent:
Zeynep Baharoglu, PhD, Institut Pasteur (France)
Summary:
Living cells transmit genetic information through three steps: DNA replication, transcription, and translation. The last step, in which the ribosome reads the genetic code and assembles proteins, is by far the noisiest. About one amino acid in every few thousand is misincorporated, a rate roughly a million times higher than that of DNA replication. These mistakes were long considered inconsequential, because the faulty proteins are quickly degraded. A more intriguing possibility has recently emerged: can mistakes in protein synthesis ultimately affect the stability of the genome itself? The little that is known about this link comes from the gut bacterium Escherichia coli.
To test whether the same principles apply more broadly, this work focused on the genus Pseudomonas, a group of bacteria found in environments ranging from soil to the human body. Translation accuracy was disrupted either by removing the enzymes that chemically modify tRNAs (TruA and RluA) at positions critical for accurate decoding, or by introducing mutations in the ribosomal protein uS5, which helps determine how strictly the ribosome distinguishes correct from incorrect codon pairing.
The findings revealed an unexpectedly intricate connection. Loss of tRNA modification raised the mutation rate of Pseudomonas putida five-fold, despite causing only modest changes in translation accuracy. Most of the uS5 mutants investigated had elevated mutagenesis, yet the variant with the strongest translation defect did not change the mutation rate at all.
Together, these findings demonstrate that translation and genome stability are closely linked, but not in a simple cause-and-effect manner: the number of translation errors alone does not determine the mutational outcome. Instead, the specific types of errors and the cellular context determine whether a fleeting mistake during protein synthesis leaves a permanent mark on the genome.
