Evolutionary Analysis of Candidate Non-Coding Elements Regulating Neurodevelopmental Genes in Vertebrates

Many non-coding regulatory elements conserved in vertebrates regulate the expression of genes involved in development and play an important role in the evolution of morphology through the rewiring of developmental gene networks. Available biological datasets allow the identification of non-coding regulatory elements with high confidence; furthermore, chromatin conformation data can be used to confirm enhancer-promoter interactions in specific tissue types and developmental stages. We have devised an analysis pipeline that integrates datasets about gene expression, enhancer activity, chromatin accessibility, epigenetic marks, and Hi-C contact frequencies in various brain tissues and developmental stages, leading to the identification of eight non-coding elements that might regulate the expression of three genes with important roles in brain development in vertebrates. We have then performed comparative sequence and microsynteny analyses in order to reconstruct the evolutionary history of the regulatory landscape around these genes; we observe a general pattern of ancient regulatory elements conserved across most vertebrate lineages, together with younger elements that appear to be mammal and primate innovations. This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://dx.doi.org/10.24072/pci.evolbiol.100035">http://dx.doi.org/10.24072/pci.evolbiol.100035</ext-link>)