Whole-transcriptome analysis of heart in bovidae reveals regulatory pathways associated with high-altitude adaptation

Abstract Background: the yak (Bos grunniens) is one of the major livestock that can survive the extremely cold, harsh and oxygen-poor conditions and provide meat, milk and transportation for Tibetans living in the Qinghai-Tibetan Plateau, and there are some cattle migrate to yak habitat but cannot survive the extremely conditions well. However, the regulatory mechanisms that drive hypoxic adaptation of yak remain elusive. Results: Thus, we collected heart tissues from Leiwuqi (LWQ) yak and their relatives, the migration cattle in LWQ yak habitat (HAC) and low-altitude cattle (LAC), respectively, for RNA sequencing, 178 co-differentially expressed protein-coding transcripts (CETs) including 6 down-regulated and 172 up-regulated CETs were discovered in both LAC-vs-LWQY and LAC-vs-HAC comparison groups. There were 133, 11 and 3 lncRNA transcripts were specific expressed in LWQY, HAC, and LAC groups, respectively. 2 and 230 lncRNA transcripts differentially expressed in LAC-vs-LWQY and LAC-vs-HAC，respectively, but no lncRNA transcripts co-differentially expressed in those two comparison groups. Among the 58 miRNAs that were co-differentially expressed, 18 were up-regulated and 40 were down-regulated. In addition, 640 (501 up-regulated and 139 down-regulated) and 152 (152 up-regulated and 1 down-regulated) circRNAs showed differential expression in LAC-vs-LWQY and LAC-vs-HAC comparison groups, respectively, and 53 up-regulated co-differentially expressed circRNAs were shared. Multiply CETs which are the target genes for miRNAs/lncRNAs were significantly enriched in high-altitude adaptation related processes, for instance, T cell receptor signaling, VEGF signaling, and cAMP signaling. A competing endogenous RNA (ceRNA) network by integrating competing relationships among CETs, miRNAs, lncRNAs and circRNAs were constructed. Furthermore, we constructed a hypoxic adaptation related ceRNA network to identified that 8 miRNAs and 15 circRNAs were predicted to regulated MAPKAPK3, PXN, NFATC2, ATP7A, DIAPH1 and F2R genes. Conclusion: In conclusion, our data reinforce the view that the molecular network of high-altitude adaptation is composed of several protein-coding transcripts and non-coding transcripts that involved in multiply hypoxic adaptation regulatory pathways. The detailed mechanism for how this network crosstalk each other in heart of Bovidae are worthy of future research efforts.