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Transcriptome profiles revealed the mechanisms underlying the adaptation of yak to high-altitude environments.

ABSTRACT: The yak is a valuable species in the Qinghai-Tibet Plateau of China. Nevertheless, the molecular mechanisms underlying its adaptation to high-altitude environments remain largely unknown. In the present study, comparative transcriptome sequencing was performed for lung and gluteus tissues from two species of low-altitude cattle (Sanjiang and Holstein cattle), Tibetan cattle (living at a moderate altitude), and yak (living at a high altitude) and the differentially expressed genes were validated using real-time quantitative PCR. The results showed that CD36 antigen was up-regulated and CD59 antigen was down-regulated in yak in comparison to the other animals, which might promote the development of red blood cells and inhibit the development of lymphocytes in yak. In addition, thrombospondin type 1, coagulation factor 5/8, and fibronectin were all down-regulated, but serpin and alpha 2-macroglobulin (A2M) were up-regulated. These differences would inhibit blood coagulation, thus reducing the risk of pulmonary edema. The expression levels of the calcium-release, potassium, and transient receptor potential channels decreased in yak, minimizing membrane depolarization and the harmful effects of pulmonary edema. Eleven KEGG pathways associated with innate immunity were more activated in yak and Tibetan cattle than in other cattle strains, which should reduce their risk of infection and disease. These changes together might facilitate the adaptation of yak and Tibetan cattle to live in high-altitude habitats.

SUBMITTER: Xin JW

PROVIDER: S-EPMC6525198 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Transcriptome profiles revealed the mechanisms underlying the adaptation of yak to high-altitude environments.

Xin Jin-Wei JW Chai Zhi-Xin ZX Zhang Cheng-Fu CF Zhang Qiang Q Zhu Yong Y Cao Han-Wen HW Ji Qiu-Mei QM Zhong Jin-Cheng JC

Scientific reports 20190517 1

The yak is a valuable species in the Qinghai-Tibet Plateau of China. Nevertheless, the molecular mechanisms underlying its adaptation to high-altitude environments remain largely unknown. In the present study, comparative transcriptome sequencing was performed for lung and gluteus tissues from two species of low-altitude cattle (Sanjiang and Holstein cattle), Tibetan cattle (living at a moderate altitude), and yak (living at a high altitude) and the differentially expressed genes were validated ...[more]

PMID: 31101838

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Project description:Purpose: The goal of this study was to reveal epigenetic differences in the microRNA transcriptomes of two organs (heart and lung) between yak and cattle. Methods: Three unrelated 2-year old adult females for both of yaks and cattle (Luxi Huang cattle) were used in this study. Two of significant hypoxia-responsive tissues (heart and lung) were rapidly collected from each carcass, washed three times with physiological saline, immediately frozen in liquid nitrogen. All frozen samples were stored at –80 °C until RNA extraction.The total RNA were extracted with Trizol (Ambion, USA). NanoDrop ND-2000 spectrophotometer (Nano Drop, DE, USA) and Bioanalyzer 2100 (Agilent Technologies, Santa Clara, CA, USA) were used to monitor the concentration and integrity of RNA, respectively. In brief, several successive steps consist the Illumina sequencing. The small RNA with length of 14-40 nt were first purified by polyacrylamide gel electrophoresis (PAGE), and then specific adapters were ligated to the purified small RNA. The ligated RNA were reverse transcribed to cDNA libraries. Finally, each library were sequenced on Genome Analyzer. Results: We identified 808 widely-expressed conserved and 697 species-specific novel miRNAs in two species. In addition, although two organs showed similar high expression miRNAs, larger differentiation was present in lung than heart between two species. In addition, miRNAs with significantly differentiated patterns of expression in two organs exhibited obvious co-operation effect in high altitude adaptation in form of miRNA family and cluster. Functional analysis revealed that a large amount of differentially expressed miRNAs were enriched in hypoxia-related pathways, such as VEGF signaling pathway, HIF-1α signaling pathway, insulin signaling pathway, DNA damage response, apoptosis, fatty acid metabolism and glucose metabolism. These results suggested the diverse degrees of epigenetic variation in different tissues between yak and cattle, and revealed extensive roles of miRNAs in high altitude adaptation. Conclusions: In this study, we illustrated the differences in the microRNA transcriptomes level for heart and lung between yak and cattle, and suggested extensive roles of miRNAs in high altitude adaptation. The work performed here will provide a typical demonstration for future deciphering the mechanism of high altitude adaptation

Project description:The mechanisms underlying yak adaptation to high-altitude environments have been investigated using various methods, but no report has focused on long non-coding RNA (lncRNA). In the present study, lncRNAs were screened from the gluteus transcriptomes of yak and their transcriptional levels were compared with those in Sanjiang cattle, Holstein cattle and Tibetan cattle. The potential target genes of the differentially expressed lncRNAs between species/strains were predicted using cis and trans models. Based on cis-regulated target genes, no KEGG pathway was significantly enriched. Based on trans-regulated target genes, 11 KEGG pathways in relation to energy metabolism and three KEGG pathways associated with muscle contraction were significantly enriched. Compared with cattle strains, transcriptional levels of acyl-CoA dehydrogenase, acyl-CoA-binding protein, 3-hydroxyacyl-CoA dehydrogenase were relatively higher and those of glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate mutase 1, pyruvate kinase and lactate/malate dehydrogenase were relatively lower in yak, suggesting that yaks activated fatty acid oxidation but inhibited glucose oxidation and glycolysis. Besides, NADH dehydrogenase and ATP synthase showed lower transcriptional levels in yak than in cattle, which might protect muscle tissues from deterioration caused by reactive oxygen species (ROS). Compared with cattle strains, the higher transcriptional level of glyoxalase in yak might contribute to dicarbonyl stress resistance. Voltage-dependent calcium channel/calcium release channel showed a lower level in yak than in cattle strains, which could reduce the Ca2+ influx and subsequently decrease the risk of hypertension. However, levels of EF-hand and myosin were higher in yak than in cattle strains, which might enhance the negative effects of reduced Ca2+ on muscle contraction. Overall, the present study identified lncRNAs and proposed their potential regulatory functions in yak.

Project description:BackgroundThe yak (Bos grunniens) is an important livestock species that can survive the extremely cold, harsh, and oxygen-poor conditions of the Qinghai-Tibetan Plateau and provide meat, milk, and transportation for the Tibetans living there. However, the regulatory network that drive this hypoxic adaptation remain elusive.ResultsThe heart tissues from LeiRoqi (LWQY) yak and their related cattle (Bos Taurus) breeds, which are two native cattle breeds located in high altitude (HAC) and low altitude (LAC) regions, respectively, were collected for RNA sequencing. A total of 178 co-differentially expressed protein-coding transcripts (co-DETs) were discovered in each of the LAC-vs-LWQY and LAC-vs-HAC comparison groups, including NFATC2, NFATC1, ENPP2, ACSL4, BAD, and many other genes whose functions were reported to be associated with the immune-system, endocrine-system, and lipid metabolism. Two and 230 lncRNA transcripts were differentially expressed in the LAC-vs-LWQY and LAC-vs-HAC comparisons' respectively, but no lncRNA transcripts that were co-differentially expressed. 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 one 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. Multiple co-DETs, which are the targets of miRNAs/lncRNAs, are significantly enriched in high-altitude adaptation related processes, such as, T cell receptor signaling, VEGF signaling, and cAMP signaling. A competing endogenous RNA (ceRNA) network was constructed by integrating the competing relationships among co-differentially expressed mRNAs, miRNAs, lncRNAs and circRNAs. Furthermore, the hypoxic adaptation related ceRNA network was constructed, and the six mRNAs (MAPKAPK3, PXN, NFATC2, ATP7A, DIAPH1, and F2R), the eight miRNAs (including miR-195), and 15 circRNAs (including novel-circ-017096 and novel-circ-018073) are proposed as novel and promising candidates for regulation of hypoxic adaptation in the heart.ConclusionIn conclusion, the data recorded in the present study provides new insights into the molecular network of high-altitude adaptation along with more detailed information of protein-coding transcripts and non-coding transcripts involved in this physiological process, the detailed mechanisms behind how these transcripts "crosstalk" with each other during the plateau adaptation are worthy of future research efforts.

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Transcriptome profiles revealed the mechanisms underlying the adaptation of yak to high-altitude environments.

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Transcriptome profiles revealed the mechanisms underlying the adaptation of yak to high-altitude environments.

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