Families of nuclear receptors in vertebrate models: characteristic and comparative toxicological perspective

Area of Science:

• Genomics
• Evolutionary Biology
• Toxicology

Background:

• Synthetic chemicals can disrupt vertebrate health by interacting with nuclear receptors (NRs).
• Limited knowledge exists on NRs in many vertebrate models used for toxicity testing.
• NRs play critical roles in various physiological processes.

Purpose of the Study:

• To comprehensively characterize nuclear receptors (NRs) across 12 vertebrate species using bioinformatics.
• To understand the evolutionary patterns and sequence conservation of NRs.
• To provide a foundation for assessing chemical impacts mediated by NRs in diverse vertebrates.

Main Methods:

• Bioinformatic analysis of NR genes in 12 vertebrate genomes.
• Phylogenetic analysis to determine evolutionary relationships.
• Sequence comparison of NR domains (DNA-binding domain and ligand-binding domain).

Main Results:

• NR gene numbers varied across species (40-42 in birds, 66-74 in teleost fishes).
• All identified NRs possessed clear human homologs and grouped into seven subfamilies (NR0B-NR6A).
• Phylogenetic analysis showed conserved NR evolution, except for some exceptions in dolphins. Ligand-binding domain sequences were less conserved than DNA-binding domains, with significant variability in PXR, CAR, DAX1, and SHP.

Conclusions:

• Vertebrate NRs exhibit conserved evolutionary trajectories, with notable exceptions.
• Sequence variability, particularly in ligand-binding domains, influences NR function and response to chemical ligands.
• This genomic characterization provides essential data for comparative toxicology and understanding NR-mediated adverse effects across vertebrates.