Molecular reconstruction of recurrent evolutionary switching in olfactory receptor specificity

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Abstract

Olfactory receptor repertoires exhibit remarkable functional diversity, but how these proteins have evolved is poorly understood. Through analysis of extant and ancestrally-reconstructed drosophilid olfactory receptors from the Ionotropic receptor (Ir) family, we investigated evolution of two organic acid-sensing receptors, Ir75a and Ir75b. Despite their low amino acid identity, we identify a common 'hotspot' in their ligand-binding pocket that has a major effect on changing the specificity of both Irs, as well as at least two distinct functional transitions in Ir75a during evolution. Moreover, we show that odor specificity is refined by changes in additional, receptor-specific sites, including those outside the ligand-binding pocket. Our work reveals how a core, common determinant of ligand-tuning acts within epistatic and allosteric networks of substitutions to lead to functional evolution of olfactory receptors.

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All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 3 and 5.

Article and author information

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Lucia L Prieto-Godino

Neural Circuits and Evolution lab, The Francis Crick Institute, London, United Kingdom

For correspondence
lucia.prietogodino@crick.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2980-362X
Hayden R Schmidt

University of Lausanne, Lausanne, Switzerland

Competing interests
The authors declare that no competing interests exist.
Richard Benton

University of Lausanne, Lausanne, Switzerland

For correspondence
Richard.Benton@unil.ch

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4305-8301

Funding

European Molecular Biology Organisation (ALTF 940-2019)

Hayden R Schmidt

Human Frontier Science Program Young Investigator Award (RGY0073/2011)

Richard Benton

Helen Hay Whitney Foundation

Hayden R Schmidt

FP7 Ideas: European Research Council (802531)

Lucia L Prieto-Godino

Cancer Research UK (FC001594)

Lucia L Prieto-Godino

Medical Research Council (FC001594)

Lucia L Prieto-Godino

Wellcome Trust (FC001594)

Lucia L Prieto-Godino

FP7 Ideas: European Research Council (615094)

Richard Benton

FP7 Ideas: European Research Council (833548)

Richard Benton

Swiss National Science Foundation Nano-Tera (20NA21_143082)

Richard Benton

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.