Proposed model of CNE evolution in the context of other major genomic events during the early vertebrate radiation. Modern bony vertebrates evolved from the chordate lineage between 650 and 450 Mya, during a period of rapid morphological change (represented here in blue and based on the Morphological Complexity Index as described in Aburomia et al. 2003). It is now generally accepted that during this period an early ancestral vertebrate underwent one, or possibly two, whole-genome duplications, generating a greatly increased repertoire of genes, which in turn may have contributed to this increase in morphological complexity. The appearance of CNEs in vertebrate genomes (red boxes adjacent to gene loci, depicted as dark boxes) can be dated prior to these large-scale duplication events, as most of the dCNEs are associated with trans-dev paralogs that derive from these ancient duplications (yellow arrows). The duplication of gene loci together with associated cis-regulatory modules generates the plasticity for genes to develop new functions (neofunctionalization) and/or to perform a subset of the functions of the parent gene (subfunctionalization). This evolution must have occurred rapidly following duplication over a relatively short evolutionary period (∼50–150 Myr) during which time dCNEs evolved in length and sequence. In contrast, in the period since the teleost–tetrapod divergence (∼450 Mya), dCNEs have had a remarkably slow mutation rate and have remained practically unchanged.
