ABSTRACT: Genome Resequencing Identifies Unique Adaptations of Tibetan Chickens to Hypoxia and High-dose Ultraviolet Radiation in High-altitude Environments
Project description:Genome Resequencing Identifies Unique Adaptations of Tibetan Chickens to Hypoxia and High-dose Ultraviolet Radiation in High-altitude Environments
Project description:Tibetan chickens exhibit specific adaptations to high-altitude conditions compared with their lowland counterparts. To illustrate the genetic mechanisms of such adaptations in highland chickens, the genomes of four highland and four lowland chicken populations were resequenced. Our results showed that genes under positive selection in highland populations were related to cardiovascular and respiratory system development, DNA repair, response to radiation, inflammation, and immune response, indicating a strong adaptation to oxygen scarcity and high-intensity solar radiation. The distribution of allele frequencies of non-synonymous single nucleotide polymorphisms between highland and lowland populations was also analyzed by chi-square test. The results showed that several differentially distributed genes with missense mutations were enriched in several functional categories, especially in blood vessel development, which were related to adaptations to hypoxia and intense radiation. RNA sequencing also revealed that several differentially expressed genes were enriched in gene ontology terms related to blood vessel and respiratory system development. Additionally, an evident admixture found in Tibetan chickens suggested a history of introgression from lowland gene pools. Overall, our data provided new insights into the unique adaptation of highland animals to extreme environments.
Project description:Tibetan chickens, a unique plateau breed, have good performances to adapt to high-altitude hypoxic environments. A number of positively selected genes have been reported in Tibetan chickens; however, the mechanisms of gene expression for hypoxia adaptation are not fully understood. In the present study, eggs from Tibetan (TC) and Chahua (CH) chickens were incubated under hypoxic and normoxic conditions, and vascularization in the chorioallantoic membrane (CAM) of embryos was observed. We found that the vessel density index (VDI) in CAM of TCs was lower than in CHs under hypoxia incubation.Proteomic analyses of CAM tissues were performed in TC and CH embryos under hypoxic incubation using iTRAQ. We obtained 387 differentially expressed proteins (DEPs) that were mainly enriched in angiogenesis, vasculature development, blood vessel morphogenesis, blood circulation, renin-angiotensin system, and HIF-1 and VEGF signaling pathways. Twenty-six genes involved in angiogenesis and blood circulation, two genes involved in ion transport, and six genes that regulated energy metabolism were identified as candidate functional genes in regulating hypoxic adaption of chicken embryos. Therefore, this research provided insights into the molecular mechanism of hypoxia adaptation in Tibetan chickens.
Project description:Background/Aims: Tibetan chickens, a unique plateau breed, have good performances to adapt to high-altitude hypoxic environments. A number of positively selected genes have been reported in Tibetan chickens; however, the mechanisms of gene expression for hypoxia adaptation are not fully understood. Methods: Eggs from Tibetan (TC) and Chahua (CH) chickens were incubated under hypoxic and normoxic conditions, and vessel density index (VDI) in the chorioallantoic membrane (CAM) of embryos was measured. Meanwhile, Transcriptomic and proteomic analyses of CAM tissues were performed in TC and CH embryos under hypoxic incubation using RNA-seq and iTRAQ. Results: We found that the vessel density index (VDI) in CAM of TCs was lower than in CHs under hypoxia incubation. In the transcriptomic and proteomic analyses, 160 differentially expressed genes (DEGs) and 387 differentially expressed proteins (DEPs) that were mainly enriched in angiogenesis, vasculature development, blood vessel morphogenesis, blood circulation, renin-angiotensin system, and HIF-1 and VEGF signaling pathways. Twenty-six genes involved in angiogenesis and blood circulation, two genes involved in ion transport, and six genes that regulated energy metabolism were identified as candidate functional genes in regulating hypoxic adaption of chicken embryos. Conclusion: Combination of transcriptomic and proteomic data revealed several key candidate regulators and pathways that might play high-priority roles in the hypoxic adaptation of Tibetan chickens by regulating angiogenesis and promoting blood circulation, thus explaining the blunt responses to hypoxic conditions on CAM angiogenesis in Tibetan chicken embryos. This research provided insights into the molecular mechanism of hypoxia adaptation in Tibetan chickens.
Project description:Tibetan chicken has a suite of adaptive features to tolerate the high-altitude hypoxic environment as a unique native breed in Qinghai-Tibet Plateau of China. Increasing evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have roles in hypoxic adaptation of high-altitude animals, though their exact contributions remain unclear. This study aims to uncover the global landscape of mRNAs, lncRNAs and miRNAs using transcriptome sequencing so as to construct a regulatory network of competing endogenous RNAs (ceRNAs) provide a new sight for the hypoxic adaptation of Tibetan chicken embryos. In the study, 354 differentially expressed mRNAs (DEGs), 389 differentially expressed lncRNAs (DELs) and 73 differentially expressed miRNAs (DEMs) were identified between Tibetan (TC) and Chahua chicken (CH). The functional analysis showed that several important DEMs and their targets of DELs and DEMs are involved in angiogenesis (include blood vessel development and blood circulation) and energy metabolism (include glucose, carbohydrate and lipid metabolism). The ceRNA network was then constructed with the predicted pairs of DEGs-DEMs-DELs which further revealed regulatory roles of these differentially expressed RNAs in hypoxic adaptation of Tibetan chicken.
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: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: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:<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>