A highland-adaptation variant near MCUR1 reduces its transcription and attenuates erythrogenesis in Tibetans.

ABSTRACT: To identify genomic regions subject to positive selection that might contain genes involved in high-altitude adaptation (HAA), we performed a genome-wide scan by whole-genome sequencing of Tibetan highlanders and Han lowlanders. We revealed a collection of candidate genes located in 30 genomic loci under positive selection. Among them, MCUR1 at 6p23 was a novel pronounced candidate. By single-cell RNA sequencing and comprehensive functional studies, we demonstrated that MCUR1 depletion leads to impairment of erythropoiesis under hypoxia and normoxia. Mechanistically, MCUR1 knockdown reduced mitochondrial Ca²⁺ uptake and then concomitantly increased cytosolic Ca²⁺ levels, which thereby reduced erythropoiesis via the CAMKK2-AMPK-mTOR axis. Further, we revealed rs6164458

SUBMITTER: Ping J 

PROVIDER: S-EPMC11960549 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature