The Evolutionary Analysis Of HIF1α Gene And Hypertension In Plateau

Hypertension disease is one of the highest incidencecardiovascular and cerebrovascular diseases, and it has a very complex pathogenesis. In the high altitude area like Qinghai-Tibet Plateau, the air pressure is high and the oxygen concentration is low,plus people in these place often like salty food and high-fat food, so the incidence of hypertension disease among high altitude people is higher. Because of the low oxygen concentration, treatment outcome of hypertension patients in high altitude area is not good enough. As the most important gene in hypoxia response, the transcription factor HIF-1 plays an important role in hypoxia response to increase the concentration of oxygen in mammals. It also known as HIF-1-alpha protein may have connection with high altitude hypertension by regulate its target genes witch may involve in hypertension’s generation and development.Living long term in high altitude area, people and other animals such as Tibetan antelope and yak, they are undergoing the natural selection to adapt the environment of low oxygen. In essence, the evolution is because of the molecular evolution, the neutral theory suggest that divergent selective pressure is an important evidence of molecular evolution. To explore variation in selective pressure among mammals in plain area and high altitude area, we used codon-based models of evolution as implemented in PAML. Tests using branch-site models and clade models that partitioned data along the altitude(plain, high altitude) found significant evidence of divergent selective pressures among high altitude groups.Besides, we investigate the function of the positive selective sites in HIF1α protein, some of the sites play an import role in hypoxia response. So the positive selection in these sites may change the protein function and target gene expression, and participate the pathogenesis of hypertensiondisease in plateau. These results may indicate the difference between hypertension in plain area and in high altitude, so that we can development unique therapy based on the specificity of high altitude disease.