It is widely accepted that animals have a relatively common set of protein-coding genes and that, notwithstanding lineage-specific innovations and splice variants, the primary basis of phenotypic, especially morphological, radiation and higher complexity has been the variation and expansion of the regulatory architecture that controls the deployment of these protein components and their isoforms during differentiation and development [71]. This regulatory architecture is generally more plastic than protein-coding sequences that are highly constrained by relatively strict structure-function relationships, which is reflected by the fact that regulatory sequences evolve at widely different rates [72]–[75]. These sequences range from promoter regions that have no recognizable sequence similarity yet direct orthologous patterns of gene expression between fishes and mammals [76] to highly conserved non-genic elements [77],[78], and “ultraconserved” sequences that have remained essentially unchanged over hundreds of millions of years of vertebrate evolution and appear to act as tissue-specific enhancers that regulate gene expression during development [79]–[82].
