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Interpreting the Evolutionary Echoes of a Protein Complex Essential for Inner-Ear Mechanosensation
Collin R Nisler1,2, Yoshie Narui3, Emily Scheib1
1Department of Chemistry and Biochemistry, The Ohio State University, 484 W 12th Avenue, Columbus, OH.
Molecular Biology and Evolution
|March 13, 2023
Summary
The evolution of cadherin-23 and protocadherin-15 proteins, crucial for hearing, shows sequence changes impact their interaction. This diversification explains variations in hearing mechanisms and deafness mutations across vertebrates.
Area of Science:
- Evolutionary biology
- Molecular biology
- Bioacoustics
Background:
- The inner ear's sensory epithelium in vertebrates has evolved over 500 million years.
- Hearing relies on cadherin-23 and protocadherin-15 proteins forming a crucial "tip-link" interaction.
- The evolutionary path and mechanical properties of these proteins are not well understood in most non-mammalian vertebrates.
Purpose of the Study:
- To investigate the evolutionary history of the cadherin-23 and protocadherin-15 interaction.
- To characterize the biophysical properties of this protein complex across vertebrate lineages.
- To understand how evolutionary changes influence the mechanics and function of the hearing apparatus.
Main Methods:
- Utilized diverse experimental techniques to analyze protein interactions.
- Employed evolutionary simulations to model sequence changes and their effects.
- Performed biophysical simulations to assess interaction strength and dynamics.
Main Results:
- Evolutionary sequence alterations significantly affect the biophysical properties of the cadherin-23/protocadherin-15 complex.
- Variations in interaction strength and dynamics were observed among different vertebrate groups.
- Evolutionary simulations revealed how biophysical properties constrain further evolution and explain mutation patterns.
Conclusions:
- Selection has modified the tip-link interface throughout vertebrate evolution.
- Subsequent neutral evolution and purifying selection have driven diversification, particularly in tetrapods.
- Understanding these evolutionary dynamics offers insights into the prevalence of deafness-causing mutations.
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