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

  • Authors
  • Walsh S, Izquierdo-Serra M, Acosta S, Edo A, Lloret M, Moret R, Bosch E, Oliva B, Bertranpetit J, Fernández-Fernández JM
  • UPF authors
  • BOSCH FUSTE, ELENA; BERTRANPETIT BUSQUETS, JAUME; OLIVA MIGUEL, BALDOMERO; FERNANDEZ FERNANDEZ, JOSE MANUEL;
  • Type
  • Scholarly articles
  • Journal títle
  • Scientific Reports
  • Publication year
  • 2020
  • Volume
  • 10
  • Number
  • 1
  • Pages
  • 0-0
  • ISSN
  • 2045-2322
  • Publication State
  • Published
  • 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.
  • Complete citation
  • Walsh S, Izquierdo-Serra M, Acosta S, Edo A, Lloret M, Moret R, Bosch E, Oliva B, Bertranpetit J, Fernández-Fernández JM. Adaptive selection drives TRPP3 loss-of-function in an Ethiopian population. Scientific Reports 2020; 10(1).
Bibliometric indicators
  • 0 times cited Scopus
  • 0 times cited WOS
  • Índex Scimago de 1.24(2020)