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The membrane receptors that appeared before their ligand: The different proposed scenarios

Abstract : The interactions between membrane receptors and their endogenous ligands are key interactions in organisms. Recently, we have shown that a high number of genes encoding human receptors appeared at the same moment as their ligand in the animal tree of life. However, a set of receptors appeared before their present ligand. Different scenarios have been proposed to explain how a receptor can be conserved if its ligand is not yet appeared. However, these scenarios have been proposed individually and have never been studied in a global way. In this study, we investigated 30 mammalian pairs of ligand/receptor for which the first ligand appeared after its receptor in the tree of life, by using common indexes of selection, and proposed different scenarios explaining the earlier appearance of a receptor relative to its ligand. Based on 3D structural studies, our indexes allowed us to classify the evolution of these partners into different scenarios: 1) a scenario where the binding interface of the receptor is already present and under purifying selection before the appearance of the ligand; 2) a scenario where the binding interface seems to have appeared progressively, and 3) a scenario where the binding site seems to have been reshuffled since its appearance. As some scenarios were confirmed by the literature, we concluded that simple indexes can give a good highlight of the evolutive history of two partners that did not appear at the same time. Based on these scenarios, we also hypothesize that the replacement of a ligand by another is a frequent phenomenon during evolution.
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Contributor : Eric Marchoux <>
Submitted on : Wednesday, February 24, 2021 - 4:07:13 PM
Last modification on : Wednesday, May 19, 2021 - 10:38:08 AM

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Anna Grandchamp, Philippe Monget. The membrane receptors that appeared before their ligand: The different proposed scenarios. PLoS ONE, Public Library of Science, 2020, 15 (5), pp.1-13. ⟨10.1371/journal.pone.0231813⟩. ⟨hal-03151281⟩

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