Replication-transcription collisions impose DNA strand-specific constraints on gene length in bacteria

Gene length directly shapes biological novelty because it is tied to encoded protein function, gene expression level, and the likelihood of mutation accumulation. Understanding the molecular and evolutionary forces that determine gene length is therefore essential for explaining how biological functions evolve. Across life, from bacteria to humans, gene lengths are tightly centered around an average of roughly 1,000–1,500 nucleotides, raising the question of what limits their evolution. In this study, we compared gene length distributions across the bacterial kingdom and found that gene length is strongly constrained in a DNA-strand-specific manner. Genes are generally shorter on the lagging strand, and longer genes tend to accumulate mutations in their regulatory regions. We propose that replication and transcription—two fundamental processes that move along DNA and often conflict with one another—create strand-specific selection pressures that limit gene length. Thus, reducing the harmful effects of replication-transcription conflicts appears to constrain gene length and shape the evolution of biological function.