Dataset Information

Adaptive selection drives TRPP3 loss-of-function in an Ethiopian population.

ABSTRACT: TRPP3 (also called PKD2L1) is a nonselective, cation-permeable channel activated by multiple stimuli, including extracellular pH changes. TRPP3 had been considered a candidate for sour sensor in humans, due to its high expression in a subset of tongue receptor cells detecting sour, along with its membership to the TRP channel family known to function as sensory receptors. Here, we describe the functional consequences of two non-synonymous genetic variants (R278Q and R378W) found to be under strong positive selection in an Ethiopian population, the Gumuz. Electrophysiological studies and 3D modelling reveal TRPP3 loss-of-functions produced by both substitutions. R278Q impairs TRPP3 activation after alkalinisation by mislocation of H⁺ binding residues at the extracellular polycystin mucolipin domain. R378W dramatically reduces channel activity by altering conformation of the voltage sensor domain and hampering channel transition from closed to open state. Sour sensitivity tests in R278Q/R378W carriers argue against both any involvement of TRPP3 in sour detection and the role of such physiological process in the reported evolutionary positive selection past event.

SUBMITTER: Walsh S

PROVIDER: S-EPMC7710729 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Adaptive selection drives TRPP3 loss-of-function in an Ethiopian population.

Walsh Sandra S Izquierdo-Serra Mercè M Acosta Sandra S Edo Albert A Lloret María M Moret Roser R Bosch Elena E Oliva Baldo B Bertranpetit Jaume J Fernández-Fernández José Manuel JM

Scientific reports 20201202 1

TRPP3 (also called PKD2L1) is a nonselective, cation-permeable channel activated by multiple stimuli, including extracellular pH changes. TRPP3 had been considered a candidate for sour sensor in humans, due to its high expression in a subset of tongue receptor cells detecting sour, along with its membership to the TRP channel family known to function as sensory receptors. Here, we describe the functional consequences of two non-synonymous genetic variants (R278Q and R378W) found to be under stro ...[more]

PMID: 33268808

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Project description:The geographic mosaic of coevolution predicts parasite virulence should be locally adapted to the host community. Cotesia parasitoid wasps adapt to local lepidopteran species possibly through their symbiotic bracovirus. The virus, essential for the parasitism success, is at the heart of the complex coevolutionary relationship linking the wasps and their hosts. The large segmented genome contained in the virus particles encodes virulence genes involved in host immune and developmental suppression. Coevolutionary arms race should result in the positive selection of particular beneficial alleles. To understand the global role of bracoviruses in the local adaptation or specialization of parasitoid wasps to their hosts, we studied the molecular evolution of four bracoviruses associated with wasps of the genus Cotesia, including C congregata, C vestalis and new data and annotation on two ecologically differentiated populations of C sesamie, Kitale and Mombasa. Paired orthologs analyses revealed more genes under positive selection when comparing the two C sesamiae bracoviruses belonging to the same species, and more genes under strong evolutionary constraint between species. Furthermore branch-site evolutionary models showed that 17 genes, out of the 54 currently available shared by the four bracoviruses, harboured sites under positive selection including: the histone H4-like, a C-type lectin, two ep1-like, ep2, a viral ankyrin, CrV1, a ben-domain, a Serine-rich, and eight unknown genes. Lastly the phylogenetic analyses of the histone, ep2 and CrV1 genes in different African C sesamiae populations showed that each gene described differently the individual relationships. In particular we found recombination had happened between the ep2 and CrV1 genes, which are localized 37.5 kb apart on the wasp chromosomes. Involved in multidirectional coevolutionary interactions, C sesamiae wasps rely on different bracovirus mediated molecular pathways to overcome local host resistance.

Dataset Information

Adaptive selection drives TRPP3 loss-of-function in an Ethiopian population.

Publications

Adaptive selection drives TRPP3 loss-of-function in an Ethiopian population.

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