Evolution of the human cold/menthol receptor, TRPM8

Area of Science:

• Evolutionary biology
• Molecular genetics
• Neuroscience

Background:

• Genes with adaptable functions, such as sensory receptors, exhibit evolutionary plasticity.
• The TRP channel family includes TRPM8, a cold and menthol receptor known for its isoforms generated by alternative mRNA processing.
• Alternative transcription, splicing, and translation contribute significantly to gene product diversity and organismal complexity.

Purpose of the Study:

• To investigate the role of alternative transcription in the evolution of human TRPM8 cold receptor forms.
• To identify and characterize novel TRPM8 alternative mRNAs and protein isoforms in human tissues.
• To trace the evolutionary origins of TRPM8 variants across ancestral species.

Main Methods:

• Identification of TRPM8 alternative mRNAs and protein isoforms in human tissues.
• Comparative genomics analysis of TRPM8 sequences across eight ancestral species.
• Experimental validation of predicted exons in mouse tissues to confirm evolutionary origins.

Main Results:

• Discovery of 33 TRPM8 alternative mRNAs, including 24 novel sequences, and their associated protein isoforms in humans.
• Detailed evolutionary history of human TRPM8 sequences, pinpointing the origin of new variants in ancestral species.
• Experimental validation confirmed the predicted evolutionary trajectory of TRPM8 diversification.

Conclusions:

• Alternative transcription has been a significant driver in the evolution of human TRPM8 cold receptor diversity.
• The TRPM8 receptor diversified early in Boreoeutheria ancestors and further diverged at the origin of Simiiformes.
• This study provides insights into the evolutionary mechanisms generating protein diversity in sensory receptors.