Accumulation of genome-wide high throughput sequencing data has helped to describe cis regulatory elements (cisRE), their precise location and genetic variation within and between species. This new data makes it possible to study the evolution of cisRE on a genome-wide scale.
Genes involved in a particular pathway are likely to be co-regulated because the genes in the pathway are switched on or off by a common signal. Since signal transduction leading to gene expression changes is mediated by transcription factors (TF) and their interaction with other cisRE such as enhancers. Any signal involved in manipulating the pathway genes may stimulate one or a few TFs and associated DNA elements. Therefore, these genes are expected to have common regulatory motifs in the promoter region of the respective genes. Enhancers play a central role in orchestrating spatiotemporally precise gene expression programs during development. The evolution and function of enhancers can give insight into inter- and intra-species phenotypic variations.
Assuming that the functional sites in DNA are under selection pressure and are more conserved than the non-functional context, we can look for conserved cisRE sites in the related species instead of searching for it in a single sequence. A cisRE is said to be a conserved RE if- 1) RE in the reference genome is completely or highly conserved. 2) RE in the reference genome lies in the highly conserved region. 3) A position at which a model predicts a RE is the same in all the species. In this work, we study the evolutionary model for various cisRE and incorporate this in an approach to identify conserved motifs that combine a probabilistic model of binding site with probabilistic models of the evolution of these motifs.