通过转录组分析探讨高原鼠兔的高原适应性进化机制

Plateau pika has become good model for the research of highland adaptation due to the unique physiological and biochemical indexes corresponding to the highland environment. Previous studies have explored the underlying molecular mechanisms of how they adapt to the plateau and a few candidate genes have been identified. However, based on the genes identified it's still very hard to understand the mechanism of highland adaptation due to it's complex pattern which involves the change of gene sequence, the divergent of gene expression and the gene-gene interaction. In order to have a systematic and comprehensive understanding of highland adaptation based on the previous analysis, we collect plateau pikas' brain and liver samples in elevation gradients and then sequence their transcriptomes. Positive selected genes are identified based on the sequence comparison with their close related species daurian pika living at low elevation; differentially expressed genes in plateau pika are also identified based on the different expression pattern with the same gene in daurian pika; finally those genes identified in this study will be incorporated into the metabolic pathways to establish their connection. After that we try to reveal the common molecular mechanisms of plateau adaptation by comparing our data to the previous data published in yak and tibetans.

由于适应低氧而产生的独特的生理生化指标使得高原鼠兔成为研究高原适应的良好模型。前期的研究也对于其高原适应的分子机制做出了探索并鉴定了少数与其高原适应相关的基因，然而由于高原适应是一个多基因共效的复杂性状，该性状涉及到基因序列的变化，基因表达的影响以及基因间的相互作用等，因此少数基因的鉴定难以清楚地阐释该性状。为了在前期的基础上更加系统以及全面地去理解高原适应的分子机制，我们通过采集三个不同海拔梯度的高原鼠兔大脑和肝脏的样品并测定其转录本序列，之后在序列水平上通过跟其低海拔近缘物种达乌尔鼠兔的比较获取其受到正选择的基因；表达水平上同样与达乌尔鼠兔的表达情况进行比较获取其差异表达基因；最后将两部分的结果整合到代谢通路建立基因互作关系，从而更系统地理解高原鼠兔的高原适应过程；在此基础上将高原鼠兔中的结果与牦牛和高原人群中已有的数据的进行比较，探讨高原适应中存在的普遍的分子机制。