Poster Presentation Society for Molecular Biology and Evolution Conference 2016

Dynamic cis-regulatory module recruitment during cardiac evolution (#594)

Michael Eichenlaub 1 , Markus Tondl 1 , Sara Alaei 1 , Jose Polo 1 , Mirana Ramialison 1
  1. ARMI, Monash University, Clayton, VIC, Australia

The heart evolved from a simple layer of contracting mesoderm in tunicates and contracting vessels in amphioxus to a more complex organ consisting of 2 chambers in teleosts, 3 in amphibians, 3.5 in reptiles, and 4 chambers in crocodiles, birds, and mammals. Although structural complexity has increased over 600 million years of evolution, astonishingly, the master control genes known to drive heart development are extremely well conserved. We hypothesise that non-coding variations trigger changes in the regulation of cardiac gene expression which contributes to distinct morphological phenotypes. To address this, we generated for the first time a genome-wide atlas of CRMs that are active in zebrafish embryonic cardiomyocytes. ChIP-seq experiments with antibodies directed against selected histone modifications were carried out which lead to an extensive description of the zebrafish cardiac-specific cis-regulatory landscape. CRM compositions were determined by analysing TFBS and motif occurrences to consolidate a vertebrate “cardiac CRM code”. By ways of comparative genomics, we then compared our zebrafish dataset to the available cardiac cis-regulatory repertoire in mouse, in order to investigate the contribution of regulatory elements to the establishment of morphological differences between the 2 speices. We identified only 8 ultra-conserved CRMs between vertebrate species that were conserved in sequence and in function, however the majority of cardiac-specific CRMs were species-specific, suggesting that cardiac evolution is driven by rapidly evolving cis-regulation.