Abstract

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.

Highlights

  • The yak (Bos grunniens) is an indigenous and rare bovine species distributed across the Qinghai-Tibet Plateau and adjacent areas at altitudes above 2500 m

  • A total of nine healthy, 4.5-year-old, non-pregnant, and unrelated adult Leiwoqi yak females (LWQY, Leiwoqi country, Changdu city, Tibet province, China, altitude: 4200 m above sea level, geographic coordinates: 96◦23 33 E 31◦27 3 N) and their two related native cattle breeds located at high altitude (HAC, Changdu city, Tibet province, altitude: 4200m above sea level, geographic coordinates: 96◦23 33 E 31◦27 3 N) and low altitude (LAC, Wenchuan country, Aba city, Sichuan province, China, altitude: 1200m above sea level, geographic coordinates: 103◦35 26 E 31◦28 36 N), were randomly selected for heart tissue sampling, with each group represented by three healthy individuals of similar body weight

  • The aim of the present study was to obtain a global view of the yak and cattle hearts transcriptome and to identify whether these elements are related to high altitude adaptability

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Summary

Introduction

The yak (Bos grunniens) is an indigenous and rare bovine species distributed across the Qinghai-Tibet Plateau and adjacent areas at altitudes above 2500 m. Through evolution over millions of years, yak have developed many anatomical and physiological traits that enable them to survive at high altitudes, such as larger lungs and hearts (Wiener et al, 2003), a shorter tongue (Shao et al, 2010), stronger environmental sensing (Wiener et al, 2003), higher energy metabolism (Wiener et al, 2003; Wang et al, 2011), and a lack of hypoxic pulmonary vasoconstriction (Wiener et al, 2003). The regulatory network that drive this hypoxic adaptation remain elusive

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