Can Unlikely Neanderthal Chloride Channel CLC-2 Gene Variants Provide Insights in Modern Human Infertility?

Cell Physiol Biochem. 2021 Jun 19;55(3):301-310. doi: 10.33594/000000376.

Abstract

Background/aims: Neanderthals, although well adapted to local environments, were rapidly replaced by anatomically modern humans (AMH) for unknown reasons. Genetic information on Neanderthals is limited restricting applicability of standard population genetics.

Methods: Here, we apply a novel combination of restricted genetic analyses on preselected physiological key players (ion channels), electrophysiological analyses of gene variants of unclear significance expressed in Xenopus laevis oocytes using two electrode voltage clamp and transfer of results to AMH genetics. Using genetic screening in infertile men identified a loss of CLC-2 associated with sperm deficiency.

Results: Increased genetic variation caused functionally impaired Neanderthals CLC-2 channels.

Conclusion: Increased genetic variation could reflect an adaptation to different local salt supplies at the cost of reduced sperm density. Interestingly and consistent with this hypothesis, lack of CLC-2 protein in a patient associates with high blood K+ concentration and azoospermia.

Keywords: Neanderthal; Chloride Channel; Sperm; Male infertility.

MeSH terms

  • Animals
  • CLC-2 Chloride Channels
  • Chloride Channels* / genetics
  • Chloride Channels* / metabolism
  • Genetic Variation*
  • Humans
  • Infertility, Male*
  • Male
  • Neanderthals* / genetics
  • Neanderthals* / metabolism
  • Oocytes / metabolism
  • Xenopus laevis

Substances

  • CLC-2 Chloride Channels
  • Chloride Channels