Molecular Evolution of Aryl Hydrocarbon Receptor Signaling Pathway Genes

Abstract

The Aryl hydrocarbon receptor is an ancient transcriptional factor originally discovered as a sensor of dioxin. In addition to its function as receptor of environmental toxins, it plays an important role in development. Although a significant amount of research has been carried out to understand AHR signal transduction pathway and its involvement in species susceptibility to environmental toxins, none of them to date has comprehensively studied its evolutionary origins. Studying evolutionary origins of molecules can inform ancestral relationships of genes. Vertebrate genome has been shaped by two rounds of whole-genome duplications at the base of vertebrate evolution approximately 600 million years ago (Mya), followed by lineage specific gene losses, which often complicate assignment of functional homology. It is crucial to understand evolutionary origins of this transcription factor and its partners, in order to distinguish orthologs from ancient non-orthologous homologs. In this study, we have investigated evolutionary origins of proteins involved in the AHR pathway. Our results provide evidence of gene loss and duplications, crucial for understanding functional connectivity of human and model species. Multiple studies have shown that 2R-ohnologs (genes and proteins that have survived from the 2R-WGD) are enriched in signaling components relevant to developmental disorders and cancer. Our findings provide a link between AHR pathways evolutionary trajectory and its possible mechanistic involvement in pathogenesis.