Evolution of modular and pleiotropic enhancers

Abstract

Cis‐regulatory elements (CREs), or enhancers, are segments of noncoding DNA that regulate the spatial and temporal expression of nearby genes. Sometimes, genes are expressed in more than one tissue, and this can be driven by two main types of CREs: tissue‐specific “modular” CREs, where different CREs drive expression of the gene in the different tissues, or by “pleiotropic” CREs, where the same CRE drives expression in the different tissues. In this perspective, we will discuss some of the ways (i) modular and pleiotropic CREs might originate; (ii) propose that modular CREs might derive from pleiotropic CREs via a process of duplication, degeneration, and complementation (the CRE‐DDC model); and (iii) propose that hotspot loci of evolution are associated with the origin of modular CREs belonging to any gene in a regulatory network.