title: Families of nuclear receptors in vertebrate models: characteristic and comparative toxicological perspective.
abstract: Various synthetic chemicals are ligands for nuclear receptors (NRs) and can cause adverse effects in vertebrates mediated by NRs. While several model vertebrates, such as mouse, chicken, western clawed frog and zebrafish, are widely used in toxicity testing, few NRs have been well described for most of these classes. In this report, NRs in genomes of 12 vertebrates are characterized via bioinformatics approaches. Although numbers of NRs varied among species, with 40-42 genes in birds to 66-74 genes in teleost fishes, all NRs had clear homologs in human and could be categorized into seven subfamilies defined as NR0B-NR6A. Phylogenetic analysis revealed conservative evolutionary relationships for most NRs, which were consistent with traditional morphology-based systematics, except for some exceptions in Dolphin (Tursiops truncatus). Evolution of PXR and CAR exhibited unexpected multiple patterns and the existence of CAR possibly being traced back to ancient lobe-finned fishes and tetrapods (Sarcopterygii). Compared to the more conservative DBD of NRs, sequences of LBD were less conserved: Sequences of THRs, RARs and RXRs were ≥90% similar to those of the human, ERs, AR, GR, ERRs and PPARs were more variable with similarities of 60%-100% and PXR, CAR, DAX1 and SHP were least conserved among species.
authors.affiliation: MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: 1] Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada [2] Department of Zoology, and Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA [3] Department of Biology &Chemistry and State Key Laboratory in Marine Pollution, City University of Hong Kong, Kowloon, Hong Kong, SAR, China.
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.affiliation: MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Hu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D016678:Genome; D006801:Humans; D023421:Models, Animal; D010802:Phylogeny; D018160:Receptors, Cytoplasmic and Nuclear / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D014714:Vertebrates / Q000235:genetics*
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear