PT - JOURNAL ARTICLE AU - Merrikh, Christopher AU - Merrikh, Houra TI - Gene inversion increases evolvability in bacteria AID - 10.1101/293571 DP - 2018 Jan 01 TA - bioRxiv PG - 293571 4099 - http://biorxiv.org/content/early/2018/04/03/293571.short 4100 - http://biorxiv.org/content/early/2018/04/03/293571.full AB - In bacteria, most genes are encoded on the leading strand, co-orienting the movement of the replication machinery with RNA polymerases. This co-orientation bias reduces the frequency of highly detrimental head-on collisions between the two machineries. This and other work set up the expectation that over evolutionary time, head-on alleles are selected against, maximizing genome co-orientation. Our findings challenge this model. Using the well-established GC skew method, we reveal the evolutionary inversion record of all chromosomally encoded genes in multiple divergent bacterial pathogens. We find that a surprisingly large number of co-oriented genes have inverted to, and are retained in the head-on orientation. Furthermore, we find that these head-on genes, (including key antibiotic resistance and virulence genes) have higher rates of nonsynonymous mutations and are more frequently under positive selection (dN/dS>1). Based on these results, we propose that bacteria increase their evolvability through gene inversion and promotion of head-on replication-transcription collisions.