text: Unlike in protein coding regions, where the assumption of  sequence conservation of functionally homologous genes have been frequently proved, there is not a clear relationship of conservation between sequences and their functions for regulatory regions. The transcriptional promoters regions are under less stringent selection, then have a higher substitutions rates, allowing transcription factor binding sites to be replaced easily be new ones arising from random mutations. Notwithstanding the sequence changes, mainly  the functions of regulatory sequences remain conserved.
  In recents years with the increase of availability of genome sequences, phylogenetic footprinting open the possibility to identify cis-elements, and then study their evolution processes. In this sense, Raijman et al., Dermitzakis et al. have developed techniques for analyzing evolutionary processes in transcription factor regions in Saccharomyces species promoters and mammalian regulatory networks respectively.
  The basis for many of these evolutionary changes in nature are probably related with events within the cis-regulatory regions involve in gene expression. The impact of variation in regulatory regions is important for disease risk due their impact in the gene expression level. Furthermore, perturbations in the binding properties of proteins encoded by regulatory genes have been linked with phenotypes effects such as, duplicated structures, homeotic transformations and novel morphologies.