co-orientation of replication and transcription preserves genome integrityco-orientation复制和转录保持基因组的完整性.pdfVIP

Co-Orientation of Replication and Transcription Preserves Genome Integrity 1 1 2 1 Anjana Srivatsan , Ashley Tehranchi , David M. MacAlpine , Jue D. Wang * 1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America, 2 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of America Abstract In many bacteria, there is a genome-wide bias towards co-orientation of replication and transcription, with essential and/or highly-expressed genes further enriched co-directionally. We previously found that reversing this bias in the bacterium Bacillus subtilis slows replication elongation, and we proposed that this effect contributes to the evolutionary pressure selecting the transcription-replication co-orientation bias. This selection might have been based purely on selection for speedy replication; alternatively, the slowed replication might actually represent an average of individual replication- disruption events, each of which is counter-selected independently because genome integrity is selected. To differentiate these possibilities and define the precise forces driving this aspect of genome organization, we generated new strains with inversions either over ,1/4 of the chromosome or at ribosomal RNA (rRNA) operons. Applying mathematical analysis to genomic microarray snapshots, we found that replication rates vary dramatically within the inverted genome. Replication is moderately impeded throughout the inverted region, which results in a small but significant competitive disadvantage in minimal medium. Importantly, replication is strongly obstructed at inverted rRNA loci in ric