Comparative analysis of long noncoding RNA and mRNA expression provides insights into adaptation to hypoxia in Tibetan sheep

Abstract

Tibetan sheep have lived on the Qinghai-Tibetan Plateau for thousands of years and have good adaptability to the hypoxic environment and strong disease resistance. However, the molecular mechanism by which Tibetan sheep adapt to this extreme environment, especially the role of genetic regulation, is still unknown. Emerging evidence suggests that long noncoding RNAs (lncRNAs) participate in the regulation of a diverse range of biological processes. To explore the potential lncRNAs involved in the adaptation to high-altitude hypoxia of Tibetan sheep, we analysed the expression profile of lncRNAs and mRNAs in the liver and lung tissues of sheep using comparative transcriptome analysis between four Tibetan sheep populations (high altitude) and one Hu sheep population (low altitude). The results showed a total of 7848 differentially expressed (DE) lncRNA transcripts, and 22,971 DE mRNA transcripts were detected by pairwise comparison. The expression patterns of selected mRNAs and lncRNAs were validated by qRT-PCR, and the results correlated well with the transcriptome data. Moreover, the functional annotation analysis based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases showed that DE mRNAs and the target genes of the lncRNAs were significantly enriched in organ morphogenesis, response to stimulus, haem binding, the immune system, arginine and proline metabolism, and fatty acid biosynthesis. The prediction of mRNA–mRNA and lncRNA–mRNA interaction networks further revealed transcripts potentially involved in adaptation to high-altitude hypoxia, and the hub genes DDX24, PDCD11, EIF4A3, NDUFA11, SART1, PRPF8 and TCONS_00306477, TCONS_00306029, TCONS_00139593, TCONS_00293272, and TCONS_00313398 were selected. Additionally, a set of target genes, PIK3R1, IGF1R, FZD6, IFNB2, ATF3, MB, CYP2B4, PSMD13, and TGFB1, were also identified as candidate genes associated with high-altitude hypoxia adaptation. In conclusion, a collection of novel expressed lncRNAs, a set of target genes and biological pathways known to be relevant for altitude adaptation were identified by comparative transcriptome analysis between Tibetan sheep and Hu sheep. Our results are the first to identify the characterization and expression profile of lncRNAs between Tibetan sheep and Hu sheep and provide insights into the genetic regulation mechanisms by which Tibetan sheep adapt to high-altitude hypoxic environments.