An asymmetric gene evolution mechanism via replication‐transcription conflicts (735.11)

Bacterial genomes are generally biased such that most genes are encoded on the leading strand, in a co‐directional manner to DNA replication. This presumably avoids the potentially detrimental head‐on collisions that occur between the replication and transcription machineries when genes are encoded on the lagging strand. However, despite this co‐orientation bias, a significant number of highly conserved and essential genes remain head‐on to replication and are encoded for on the lagging strand. Our work, in the model organism Bacillus subtilis , led to the hypothesis that bacterial cells keep some genes in the head‐on orientation, in part, to accelerate their adaptive evolution in a targeted manner. Using both bioinformatics analyses and experimental data, we proposed that this targeted evolution mechanism is driven, at least in part, by the collisions between replication and transcription machineries. Our recent unpublished results are consistent with this hypothesis, and indicate that the asymmetric nature of how these conflicts impact the genome is indeed the major driving force behind this targeted and orientation‐dependent mutagenesis mechanism. Altogether, these findings have deepened our understanding of the impact of replication‐transcription conflicts on asymmetric mutagenesis, genome organization and evolution in bacteria. Because the underlying mechanisms are highly conserved in many species, this work potentially has far‐reaching implications beyond the bacterial world. Grant Funding Source : Supported by NIH DP2GM110773