Aryl hydrocarbon receptors: diversity and evolution.

Area of Science:

• Biochemistry
• Evolutionary Biology
• Toxicology

Background:

• Animals possess inducible enzymatic defenses for biotransformation and elimination of environmental toxins.
• Soluble receptors, including the aryl hydrocarbon receptor (AHR), regulate these defenses in response to chemicals.
• The AHR, while crucial for xenobiotic metabolism, has poorly understood physiological roles, and its disruption by dioxins causes toxicity.

Purpose of the Study:

• To review the diversity and evolution of the AHR signaling pathway across animal species.
• To understand the physiological significance of AHR by studying its structure, function, and regulation in diverse taxa.
• To infer the evolutionary history of the AHR through comparative molecular studies.

Main Methods:

• Comparative molecular studies across diverse animal species (mammals, birds, fish, invertebrates).
• Phylogenetic analysis to infer evolutionary relationships and gene duplication events.
• Characterization of AHR structure, function, and regulation in various model organisms.

Main Results:

• The AHR gene has duplicated and diversified in vertebrates, yielding AHR1, AHR2, and AHR repressor.
• Invertebrate AHR homologs cannot bind dioxins, suggesting xenobiotic metabolism regulation by AHR is a vertebrate innovation.
• Physiological developmental roles of AHR appear ancestral, with dioxin-binding capacity evolving later in vertebrates.

Conclusions:

• The AHR pathway's role in xenobiotic metabolism is likely a vertebrate evolutionary innovation.
• The evolution of dioxin-binding capacity in AHR correlates with sensitivity to dioxin developmental toxicity in vertebrates.
• Understanding AHR evolution provides insights into both its physiological functions and toxicological impacts.