Abstract
After the genomic era, the development of high-throughput sequencing technologies has allowed us to advance our understanding of genetic variants responsible for adaptation to high altitude in humans. However, transcriptomic characteristics associated with phenotypic plasticity conferring tolerance to acute hypobaric hypoxic stress remain unclear. To elucidate the effects of hypobaric hypoxic stress on transcriptional variability, we aimed to describe transcriptomic profiles in response to acute hypobaric hypoxia in humans. In a hypobaric hypoxic chamber, young Japanese males were exposed to a barometric pressure of 493 mmHg (hypobaric hypoxia) for 75 min after resting for 30 min at the pressure of 760 mmHg (normobaric normoxia) at 28°C. Saliva samples of the subjects were collected before and after hypobaric hypoxia exposure, to be used for RNA sequencing. Differential gene expression analysis identified 30 significantly upregulated genes and some of these genes may be involved in biological processes influencing hematological or immunological responses to hypobaric hypoxic stress. We also confirmed the absence of any significant transcriptional fluctuations in the analysis of basal transcriptomic profiles under no-stimulus conditions, suggesting that the 30 genes were actually upregulated by hypobaric hypoxia exposure. In conclusion, our findings showed that the transcriptional profiles of Japanese individuals can be rapidly changed as a result of acute hypobaric hypoxia, and this change may influence the phenotypic plasticity of lowland individuals for acclimatization to a hypobaric hypoxic environment. Therefore, the results obtained in this study shed light on the transcriptional mechanisms underlying high-altitude acclimatization in humans.
Highlights
High altitude is a hostile environment for humans owing to low oxygen availability through decreased barometric pressure (PB), and high-altitude illness such as acute mountain sickness in lowlanders can occur at altitudes above 2100 m (World Health Organization, 2012)
A total of 307 million reads (51 ± 7 million reads) were obtained using RNA sequencing (RNA-seq) from the six saliva samples belonging to the three Japanese individuals, to compare their transcriptomic profiles before and after exposure to acute hypobaric hypoxia
Using the DESeq2 program, we conducted the differential gene expression analysis and identified 30 differentially expressed genes (DEGs) being upregulated after exposure to acute hypobaric hypoxia (FDR < 0.05, log2 fold changes (LFC) ≥ 1), while none of the significantly downregulated genes were detected (Table 1)
Summary
High altitude is a hostile environment for humans owing to low oxygen availability through decreased barometric pressure (PB), and high-altitude illness such as acute mountain sickness in lowlanders can occur at altitudes above 2100 m (World Health Organization, 2012). While all three populations have settled at high altitudes for millennia, these populations are considered to have adapted to high altitude environments via different genetic variants (Bigham, 2016). It was estimated that ∼140 million people lived at altitudes above 2500 m across the world (Moore et al, 1998). 13.7, 1.7, and 20.7 million people were estimated to live in Ethiopia, Tibet, and South American Andes, respectively. Recent high-throughput genome sequencing studies have contributed to finding signals of positive natural selection acting on genes associated with hematological or pulmonary traits in people residing at high altitudes and revealed that genes in the hypoxiainducible factor (HIF) pathway are responsible for high-altitude adaptation in highland populations (Bigham, 2016)
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