Differential use of paralogous genes via evolution of cis-regulatory elements for divergent expression specificities

Abstract

Recent accumulation of genome sequences indicates that vertebrate genomes retained many duplicate genes, called paralogues, after whole-genome duplications (WGDs) occurring in the early stages of chordate evolution. Although paralogous gene pairs probably had the same expression patterns immediately after WGDs, they often showed distinct expression patterns in modern vertebrates. Nucleotide sequence changes in noncoding genomic regions, including cis-regulatory elements (CRE) such as enhancers and silencers, are the primary cause of the divergent paralogue expression. Such CRE evolution can be classified as follows: (1) enhancer innovation, (2) silencer innovation, and (3) ancestral CRE degeneration. In this chapter, we first show examples of the degeneration of ancestral CREs, with reference to the duplication-degeneration-complementation model, and subsequently introduce recently discovered evidence for silencer innovation and conservation of ancestral pleiotropic enhancers. Finally, we discuss the possible involvement of enhancer innovation in the divergent paralogue expression.