Project

Pervasive transcription, i.e. spurious genome-wide production of unfunctional transcripts, often in antisense to coding genes, is a universal yet ambiguous property of all genomes. It is traditionally viewed as an undesirable by-product of RNAP-driven “functional” transcription that poses multiple threats to genome stability and global gene expression. This is why apparently all organisms have evolved specific molecular mechanisms to manage pervasive transcripts, such as co-transcriptional suppression of undesirable transcripts by the termination factor Rho and post-transcriptional degradation of hybrids formed between sense and antisense RNAs by RNase III. This said, pervasive transcription is never fully repressed and even plays important biological roles, e.g. in transcription-coupled DNA repair, buffering of naturally bursty transcription of sense genes, and gene expression regulation. Associated with increased mutagenesis and calling to life novel RNAs, it is expected to be an important creative force in genome and transcriptome plasticity and may significantly affect adaptability of living organisms. While immediate deleterious consequences of uncontrolled pervasive antisense transcription (“here and now”) are well-documented, research into its potentially positive long-term, evolutionary facet remains scarce. The present project fills this gap by directly interrogating the longitudinal impact of pervasive transcription in an important human pathogen, Staphylococcus aureus, using a controlled experimental evolution set-up. Conducted by a consortium of RNA and evolutionary biologists, this project will follow in real time how microbial populations with unleashed pervasive transcription adapt to such a drastic change in their transcriptome, what kind of genomic, transcriptomic and phenotypic alterations they acquire, and how much their evolutionary trajectories differ from those of wild-type bacteria.