Co-orientation of replication and transcription preserves genome integrity.

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 approximately 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 rich medium. This obstruction results in disruption of DNA replication, activation of DNA damage responses, loss of genome integrity, and cell death. Our results strongly suggest that preservation of genome integrity drives the evolution of co-orientation of replication and transcription, a conserved feature of genome organization.

Spatial imagery preserves temporal order.

Line drawings were presented in either a spatial or a nonspatial format. Subjects recalled each of four sets of 24 items in serial order. Amount recalled in the correct serial order and sequencing errors were scored. In Experiment 1 items appeared either in consecutive locations of a matrix or in one central location. Subjects who saw the items in different locations made fewer sequencing errors than those who saw each item in a central location, but serial recall levels for these two conditions did not differ. When items appeared in nonconsecutive locations in Experiment 2, the advantage of the spatial presentation on sequencing errors disappeared. Experiment 3 included conditions in which both the consecutive and nonconsecutive spatial formats were paired with retrieval cues that either did or did not indicate the sequence of locations in which the items had appeared. Spatial imagery aided sequencing when, and only when, the order of locations in which the stimuli appeared could be reconstructed at retrieval.