Comparative Analysis of Long Non-Coding RNA and mRNA Expression Provides Insights Into Adaptation to Hypoxia in Tibetan Sheep

doi:10.21203/rs.3.rs-77480/v2

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Comparative Analysis of Long Non-Coding RNA and mRNA Expression Provides Insights Into Adaptation to Hypoxia in Tibetan Sheep

https://doi.org/10.21203/rs.3.rs-77480/v2

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Tibetan sheep have lived on the Qinghai-Tibetan Plateau for thousands of years and they have a good adaptability to the hypoxic environment and strong disease resistance. However, the molecular mechanism of the Tibetan sheep adapting to this extreme environment, especially the role of genetic regulation is still unknown. Emerging evidence suggests that long non-coding RNAs (lncRNAs) participate in the regulation of a diverse range of biological processes. To explore the potential lncRNAs involved in Tibetan sheep adapting to high altitude hypoxia environment, we analyzed the expression profile of lncRNAs and mRNAs in liver and lung tissue of sheep based on the comparative transcriptome analysis between four Tibetan sheep populations (high altitude) and Hu sheep (low altitude). The results showed a total of 7848 differentially expressed (DE) lncRNAs transcripts and 22971 DE mRNAs 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, heme binding, 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, the hub genes that DDX24, PDCD11, EIF4A3, NDUFA11, SART1, PRPF8 and TCONS_00306477, TCONS_00306029, TCONS_00139593, TCONS_00293272, 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 aberrantly expressed lncRNA, 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 first identified the characterization and expression profile of lncRNAs between Tibetan sheep and Hu sheep and provides insights into the genetic regulation mechanisms for Tibetan sheep adaptation to high altitude hypoxia environments.

Biotechnology and Bioengineering

Epigenetics & Genomics

Molecular Biology

Tibetan sheep

transcriptome

lncRNAs

mRNAs

hypoxia

Due to technical limitations, tables are only available as a download in the Supplemental Files section.

No competing interests reported.

Table1.pdf
Table 1: Sampling information of five sheep populations (Ovis aries) for transcriptome analysis.
Table2.pdf
Table 2: The candidate genes putatively associated with the plateau adaptation of Tibetan sheep.
TableS1.xlsx
Table S1: The primers for mRNAs and lncRNAs.
TableS2.xlsx
Table S2: The determination results of the physiological and biochemical indices of five sheep populations.
TableS3.xlsx
Table S3: Statistics of clean reads of liver and lung tissue samples from five sheep populations.
TableS4.xlsx
Table S4: Identification of lncRNAs and mRNAs in sheep liver and lung tissue.
TableS5.xlsx
Table S5: The DE mRNAs and lncRNAs in all groups by pairwise comparison.
TableS6.xlsx
Table S6: The DE mRNAs and lncRNAs of the pairwise comparison between Tibetan sheep and Hu sheep (AW vs HS, HB vs HS, GJ vs HS, WT vs HS).
TableS7.xlsx
Table S7: Annotation of DE mRNAs and the targeted genes of DE lncRNAs.
TableS8.xlsx
Table S8: Significantly enriched GO terms and KEGG pathways of targeted genes of DE lncRNAs.
TableS9.xlsx
Table S9: The top 10 DE mRNAs with the highest degree and lncRNAs that interacted with more target genes.
TableS10.xlsx
Table S10: qRT-PCR verification of 7 DE lncRNAs, 13 target genes, and 20 DE mRNAs.
FigureS1.tif
Fig. S1: Identification of long non-coding RNAs (lncRNAs) and mRNAsI involved in high altitude hypoxia adaptation in liver tissue. Coding potentiality filter using Coding Potential Calculator, Pfam, Phylogenetic codon substitution frequency, and Coding-Non-Coding Index (A). The boxplot shows the expression levels (log10 (FPKM +1)) of lncRNAs and mRNAs (B). Transcript lengths distribution of mRNAs (C) and lncRNAs (D). Exon number distribution of mRNAs (E) and lncRNAs (F). Open reading frame (ORF) length distribution of mRNAs (G) and lncRNAs (H).
FigureS2.tif
Fig. S2: The correlation coefficient of all liver and lung samples. The correlation coefficient tends toward 1 between samples from the same group indicating that it is reasonable to perform further data analyses
FigureS3.tif
Fig. S3: The circus plot of the chromosomal distribution of DE lncRNAs and mRNAs in (A) liver and (B) lung tissue. The outermost ring represents different chromosomes. From outer ring to inner ring in order as mRNA (AW vs HS), lncRNA (AW vs HS), mRNA (HB vs HS), lncRNA (HB vs HS), mRNA (GJ vs HS), lncRNA (GJ vs HS), mRNA (WT vs HS), lncRNA (WT vs HS). 1< log2FC <5 (orange), 5< log2FC <Inf (yellow), log2FC =Inf (red), -5< log2FC <-1 (purple), -Inf< log2FC <5 (blue), log2FC =-Inf (green).
FigureS4.tif
Fig. S4: Interaction network of DEGs in five sheep populations from different altitude. (A) mRNA–mRNA interaction network of DE mRNAs in liver tissue. (B) mRNA–mRNA interaction network of DE mRNAs in lung tissue. (C) lncRNA–mRNA interaction network in liver tissue. (D) lncRNA–mRNA interaction network in lung tissue. Circles and squares represent mRNAs and lncRNAs, respectively.

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Editorial decision: Major revision
16 Jul, 2021
Reviews received at journal
11 Jul, 2021
Reviewers agreed at journal
07 Jul, 2021
Reviewers invited by journal
07 Jul, 2021
Editor assigned by journal
07 Jul, 2021
Editor invited by journal
28 Jun, 2021
Submission checks completed at journal
28 Jun, 2021
First submitted to journal
16 Jun, 2021

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Comparative Analysis of Long Non-Coding RNA and mRNA Expression Provides Insights Into Adaptation to Hypoxia in Tibetan Sheep

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