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Front. Mol. Biosci. | doi: 10.3389/fmolb.2018.00009

Independent Evolution of Strychnine Recognition by Bitter Taste Receptor Subtypes

 Yuan (Ava) Xue1, 2, Antonella DiPizio1, Anat Levit3, Tali Yarnitzky1, Osnat Penn4, Tal Pupko5 and  Masha Y. Niv1, 2*
  • 1The Hebrew University of Jerusalem, Israel
  • 2The Fritz Haber Center for Molecular Dynamics, The Hebrew University, Israel
  • 3University of California, San Francisco, United States
  • 4Allen Institute for Brain Science, United States
  • 5Tel Aviv University, Israel

The 25 human bitter taste receptors (hT2Rs) recognize thousands of structurally and chemically diverse bitter substances. The binding modes of human bitter taste receptors hT2R10 and hT2R46, which are responsible for strychnine recognition, were previously established using site-directed mutagenesis, functional assays and molecular modeling. Here we construct a phylogenetic tree and reconstruct ancestral sequences of the T2R10 and T2R46 clades. We next analyze the binding sites in view of experimental data to predict their ability to recognize strychnine. This analysis suggests that the common ancestor of hT2R10 and hT2R46 is unlikely to bind strychnine in the same mode as either of its two descendants. Estimation of relative divergence times shows that hT2R10 evolved earlier than hT2R46. Strychnine recognition was likely acquired first by the earliest common ancestor of the T2R10 clade before the separation of primates from other mammals, and was highly conserved within the clade. It was probably independently acquired by the common ancestor of T2R43-47 before the homo-ape speciation, lost in most T2Rs within this clade, but enhanced in the hT2R46 after humans diverged from the rest of primates. Our findings suggest hypothetical strychnine T2R receptors in several species, and serve as an experimental guide for further study. Improved understanding of how bitter taste receptors acquire the ability to be activated by particular ligands is valuable for the development of sensors for bitterness and for potential toxicity.

Keywords: Bitter taste receptor, Homology Modeling, ligand recognition, chemosensory, evolution, ancestor functionality, ancestral reconstruction, phylogeny

Received: 24 Sep 2017; Accepted: 19 Jan 2018.

Edited by:

Piero A. Temussi, University of Naples Federico II, Italy

Reviewed by:

Tiina A. Salminen, Åbo Akademi University, Finland
Mercedes Alfonso-Prieto, Forschungszentrum Jülich, Germany
Alejandro Giorgetti, University of Verona, Italy  

Copyright: © 2018 Xue, DiPizio, Levit, Yarnitzky, Penn, Pupko and Niv. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Masha Y. Niv, NIV., The Hebrew University of Jerusalem, The Institute of Biochemistry Food and Nutrition, Rehovot, The Robert H Smith Faculty of Agriculture, Food and Environment,, Rehovot, 7610000, Israel, Israel,