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Minich DM, Brown BI

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Based on converging evolutionary and mechanistic evidenceencompassing mitochondrial centrality in hypoxic response, natural selection of the Tibetan-enriched mitochondrial DNA haplogroup M9a, and bidirectional ROS-HIF regulatory crosstalkwe propose a mechanistic hypothesis that mitochondrial retrograde signaling orchestrates nuclear genomic reprogramming through modulation of HIF-responsive elements to establish hypoxia-tolerant phenotypes