GENE DIVERGENCE OF ARYL HYDROCARBON RECEPTORS (AHR) IN EARLY VERTEBRATES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Adverse health effects from exposure to dioxin-like compounds are in part mediated through activation of aryl hydrocarbon receptors (AHR), expression of genes encoding biotransformation enzymes, and dysregulation of numerous genes outside the toxic response pathway. AHR proteins have non-transcriptional roles in cell physiology in the absence and presence of AHR ligands. Thus, it is difficult to distinguish AHR-dependent toxic response mechanisms from the perturbation of endogenous function of AHR. We study the divergence of function among multiple AHR paralogs in early vertebrates so we may separately test the pleiotropic functions of the single mammalian AHR. Our previous studies demonstrate that each product of the AHR gene both overlap and diverge in subcellular location and function. In the current study, undergraduate student projects aim to assess the function of shark AHRs in cellular processes, embryonic development of egg-laying marine vertebrates, and to investigate the relationships of these early vertebrate AHR genes with those of primates using comparative genomics. We aim to develop an effective paradigm to separately test hypotheses about subsets of mammalian AHR gene targets and non-transcriptional AHR protein function. Results from our research will provide information relevant to human responses to environmental AHR agonist exposure, and the relationship between environmental health and embryonic development.