Genomes are the richest data source to understand human biology, disease and past evolutionary history. As in the geological record, multiple evolutionary strata are contained in our DNA, from recent changes which appeared after the divergence from our extinct Neanderthal relatives, to extremely ancient genes operating basic cellular functions shared even with bacterial species. In this Russian doll-like pattern, we can recognize the nested layers of genomic traits that we specifically share with other primates, vertebrates, chordates, metazoans, etc, allowing a better understanding of our genotype-phenotype map and the unique combination of novel and ancestral traits that define our species. However, before the project EVOREL, these questions had been studied by focusing almost exclusively on the evolution of protein coding genes, but not the regulatory elements controlling their expression, severely limiting the understanding of our own genetic makeup as vertebrates. Thus, the aim of EVOREL was to fill this gap and understand the evolution and origin of specific genomic features that regulate the genes of vertebrates and are responsible for our characteristic morphology.
All chordates share a fundamental bodyplan that was greatly elaborated in vertebrates. Vertebrates also evolved highly distinctive genomes, sculpted by two whole genome duplications (WGD) that generated extra gene copies for every gene in the genome and the acquisition of unique genomic traits. To investigate the evolution of these features and genome regulation in vertebrates, we needed to identify and characterize the gene regulatory elements of a close animal relative of vertebrates that would allow us to perform meaningful genomic comparisons. To that end, we chose the cephalochordate amphioxus, a slow-evolving non-vertebrate chordate that shares many anatomical and genomic features with vertebrates and whose genome has not undergone WGDs. By comparing amphioxus regulatory elements with those of vertebrates, our aim was to identify the core genomic regulatory landscape organization that we and other vertebrates share and that underlie the novel and conserved features that characterize our body plan. This way we wanted to make ground breaking advances in our understanding of how the regulatory architecture of our genome was assembled during evolution, providing new insights on how gene regulatory organization has impacted gene expression and, ultimately, unveiling the deep evolutionary roots of the human regulatory architecture.
