Pervasive Divergence of Transcriptional Gene Regulation

Because there is considerable variation in gene expression even between closely related species, it is clear that gene regulatory mechanisms evolve relatively rapidly. Because primary sequence conservation is an unreliable proxy for functional conservation of cis-regulatory elements, their assessment must be carried out in vivo. We conducted a survey of cis-regulatory conservation between C. elegans and closely related species C. briggsae, C. remanei, C. brenneri, and C. japonica. We tested enhancers of eight genes from these species by introducing them into C. elegans and analyzing the expression patterns they drove. Our results support several notable conclusions. Most exogenous cis elements direct expression in the same cells as their C. elegans orthologs, confirming gross conservation of regulatory mechanisms. However, the majority of exogenous elements, when placed in C. elegans, also directed expression in cells outside endogenous patterns, suggesting functional divergence. Recurrent ectopic expression of different promoters in the same C. elegans cells may reflect biases in the directions in which expression patterns can evolve due to shared regulatory logic of coexpressed genes. The fact that, despite differences between individual genes, several patterns repeatedly emerged from our survey, encourages us to think that general rules governing regulatory evolution may exist and be discoverable