Project description:To explore the exceptional mechanisms of gene expression and DNA methylation that are induced by low altitude environments in Tibetan pigs, we performed a comparative transcriptomic analysis of skeletal muscle in indigenous Tibetan pigs that reside in high altitude regions (~4,000 m) and their counterparts that migrated to the geographically neighboring low-altitude regions (~500 m) for nearly ten generations. We identified protein coding genes that related to hypoxia response (EGLN3 and FLT1), oxygen transport and energy metabolism (TFB2M), and two long non-coding RNAs (TCONS_00039686 and TCONS_00084992) that associated with the regulation of transcription and various nucleolus and organelle lumen, were differentially expressed between Tibetan pigs and their counterparts in low-altitude regions, thus might be the potential candidate regulators in skeletal muscle of low-altitude acclimation in Tibetan pigs. We also found genes embedded in differentially methylated regions between Tibetan pigs and their counterparts in low-altitude regions were mainly involved in ‘Starch and sucrose metabolism’, ‘glucuronosyltransferase activity’ processes, hypoxia and energy metabolism. We envision that this study will serve as a valuable resource for mammal acclimatization research and agricultural food industry.
Project description:To explore the exceptional mechanisms of gene expression and DNA methylation that are induced by low altitude environments in Tibetan pigs, we performed a comparative transcriptomic analysis of skeletal muscle in indigenous Tibetan pigs that reside in high altitude regions (~4,000 m) and their counterparts that migrated to the geographically neighboring low-altitude regions (~500 m) for nearly ten generations. We identified protein coding genes that related to hypoxia response (EGLN3 and FLT1), oxygen transport and energy metabolism (TFB2M), and two long non-coding RNAs (TCONS_00039686 and TCONS_00084992) that associated with the regulation of transcription and various nucleolus and organelle lumen, were differentially expressed between Tibetan pigs and their counterparts in low-altitude regions, thus might be the potential candidate regulators in skeletal muscle of low-altitude acclimation in Tibetan pigs. We also found genes embedded in differentially methylated regions between Tibetan pigs and their counterparts in low-altitude regions were mainly involved in ‘Starch and sucrose metabolism’, ‘glucuronosyltransferase activity’ processes, hypoxia and energy metabolism. We envision that this study will serve as a valuable resource for mammal acclimatization research and agricultural food industry.
Project description:We investigated the heart tissue whole-genome DNA methylation data of Tibetan and Yorkshire pigs raised at high and low altitudes using MeDIP-seq (methylated DNA immunoprecipitation sequencing) technologies, in order to comparatively analyze epigenetic regulation in the two breeds under normoxic and hypoxic conditions. In addition, we aimed to identify the key genes and molecular mechanisms that are involved in adaptation to high altitude in the Tibetan pig. The results of bisulphite sequencing and RT-qPCR indicated that the differentially methylated genes identified in MeDIP-seq were credible. Our results provide new insights into the molecular mechanisms and the epigenetic mechanism involved in hypoxic adaptation in pigs, and a greater understanding of human hypoxic diseases.
Project description:Tibetan's adaptation to high-altitude environment at the Qinghai-Tibetan plateau represents a remarkable case of natural selection during recent human evolution. We generated time series paired RNAseq, ATACseq and Hi-C data in Tibetan and Han Chinese's umbilical endothelial cells from normoxia to hypoxia condition. Our results provide a broad resource of genome-wide hypoxia regulatory network to characterize the effect of genetic variation in high-altitude adaptation, and indicates large-scale maps of variants need proper cell types to understand its act on gene regulation.
Project description:In this study, miRNA-seq technique was used to identify differentially expressed miRNAs (DE miRNAs) in cardiac muscle of the Tibetan pig (TP) and Yorkshire pig (YP), which were both raised in highland environments. We obtained 108 M clean reads and 372 unique miRNAs that included 210 known pre-miRNAs and 162 novel pre-miRNAs. In addition, 20 DE miRNAs, including 10 upregulated and 10 downregulated miRNAs, were identified by comparing TP and YP. Based on the expression abundance and differentiation between the two populations, we predicted their targets, and KEGG pathway analyses suggested that DE miRNAs between the Tibetan pigs and Yorkshire pigs are involved in hypoxia-related pathways, such as the MAPK, mTOR, and VEGF signaling pathways, cancer-related signaling pathways, etc. Five DE miRNAs were randomly selected to validate the veracity of miRNA-seq using real-time PCR. The results showed that the expression corresponds to the trend in miRNA-seq, hence the deep-sequencing methods were feasible and efficient. This study expanded the number of hypoxic-adaptation-related miRNAs in pig and indicated that the expression patterns of hypoxia-related miRNAs are significantly altered in the Tibetan pig. DE miRNAs may play important roles in hypoxic adaptation after migration to hypoxic environments. mRNA profiles of 6-month old Tibetan pig (TP) and Yorkshire pig (YP) were generated by deep sequencing, in duplicate, using Hiseq 2000.
Project description:Background: Tibetan chicken, a unique plateau breed, has a suite of adaptive features that enable it to tolerate the high-altitude hypoxic environment. HIF‐1α (hypoxia inducible factor 1 subunit alpha) is a crucial mediator of the cellular response to hypoxia. HIF‐1α maintains oxygen homeostasis by inducing glycolysis, erythropoiesis, and angiogenesis; however, the target genes involved in adaptive responses to hypoxia in animals and birds of plateaus are still unclear. Results: We used ChIP-seq to map HIF‐1α binding regions in chorioallantoic membrane (CAM) tissue of chicken embryos, and identified 752 HIF-1α target genes (TG), of which 112 were differentially expressed target genes (DTGs) between the two breeds. We found that eight genes (PTK2, GPNMB, CALD1, SLC25A1, SPRY2, NUPL2, RANBPL, and CBWD1) play important roles in hypoxic adaption by regulating blood vessel development, energy metabolism through angiogenesis, vascular smooth muscle contraction, and various hypoxia-related signaling pathways (including VEGF and MAPK) in Tibetan chickens during embryonic development. Conclusions: This study enhances our understanding of the molecular mechanisms of hypoxic adaptation in Tibetan chickens and provides new insights into adaptation to hypoxia in humans and other species living at high altitude.
Project description:This data was used to identify regions of the genome that have undergone positive selection in a high-altitude Tibetan population. Affymetrix SNP arrays were used to genotype DNA extracted from blood samples. This data was used to perform genome-wide scans of positive selection in a native high-altitude Tibetan population.
Project description:To elucidate further molecular mechanisms underlying the regulation of hypoxia-adaptive phenotypes in Tibetan pigs, we used transcriptome microarrays from lung tissues of Tibetan pigs and Duroc pigs both at high and low altitude analyzed differentially expressed genes (DEGs), biological pathway and constructed co-expression regulation network. A total of 3,068 DEGs were identified which involved metabolic process, cellular process, immune biological process and angiogenesis pathway. The regulatory (RIF) and phenotypic (PIF) impact factors analysis identified several known and potentially regulators of hypoxia adaption, including IKBKG, KLF6 and RBPJ (RIF1), SF3B1, EFEMP1, HOXB6 and ATF6 (RIF2).
2016-07-15 | GSE84409 | GEO
Project description:Gut microbiota related to high altitude adaptation in Tibetan humans and pigs
Project description:<p>Due to a unique adaptation to high altitude, the Tibetan Plateau population has been the subject of much research interest. In this study, we conducted whole genome sequencing of 27 Tibetan individuals. Through our analysis, we inferred a detailed history of demography and revealed the natural selection of Tibetan population. We provided evidence of genetic separation between the two subpopulations of Han and Tibetans as early as 44 to 58 thousand years ago, replicated previously reported high altitude adaptation genes, including <i>EPAS1</i> and <i>EGLN1</i>, and reported three new candidate genes, including <i>PTGIS</i>, <i>VDR</i>, and <i>KCTD12</i>.</p>