The acquisition of cold sensitivity during TRPM8 ion channel evolution

Area of Science:

• Evolutionary biology
• Molecular biology
• Thermosensation

Background:

• Molecular thermosensors are crucial for animals to detect temperature changes.
• Transient receptor potential melastatin 8 (TRPM8) is a well-characterized cold sensor.
• Understanding TRPM8's cold sensitivity requires examining its evolutionary emergence and thermodynamic basis.

Purpose of the Study:

• To investigate the evolutionary trajectory of the TRPM8 gene and its cold-sensing capabilities.
• To elucidate the roles of specific TRPM8 domains in the development of thermosensitivity.
• To explore the link between TRPM8 evolution and terrestrial adaptation.

Main Methods:

• Comparative genomic analysis of trpm8 orthologs across vertebrate species.
• Functional characterization of TRPM8 domains in different evolutionary lineages.
• Identification of evolutionary pressures, such as positive selection, acting on TRPM8.

Main Results:

• The trpm8 gene evolved through the formation and regulation of MHR1-3 and pore domains.
• An early, non-functional trpm8 gene exists in lobe-finned fishes.
• A mature MHR1-3 domain conferring cold sensitivity evolved in amphibians and reptiles.
• Positive selection on the TRPM8 pore domain occurred later in terrestrial tetrapods.
• The MHR1-3 domain is essential for the pore domain's cold-activation regulation.

Conclusions:

• TRPM8's cold sensitivity evolved in a domain-dependent manner.
• The acquisition of TRPM8 cold sensitivity was a key factor in vertebrate terrestrial adaptation.
• Evolutionary insights into TRPM8 provide a model for understanding thermosensor development.