Comparative microRNA Transcriptomes in Domestic Goats Reveal Acclimatization to High Altitude

Abstract

High-altitude acclimatization is a representative example of vertebrates' acclimatization to harsh and extreme environments. Previous studies reported sufficient evidence for a molecular genetic basis of high-altitude acclimatization, and genomic patterns of genetic variation among populations and species have been widely elucidated in recent years. However, understanding of the miRNA role in high-altitude acclimatization have lagged behind, especially in non-model species. To investigate miRNA expression alterations of goats that were induced by high-altitude stress, we performed comparative miRNA transcriptome analysis on six hypoxia-sensitive tissues (heart, kidney, liver, lung, skeletal muscle, and spleen) in two goat populations from distinct altitudes (600 and 3000 m). We obtained the expression value of 1391 mature miRNAs and identified 138 differentially expressed (DE) miRNAs between high and low altitudes. Combined with tissue specificity analysis, we illustrated alterations of expression levels among altitudes and tissues, and found that there were coexisting tissue-specific andconserved mechanisms for hypoxia acclimatization. Notably, the interplay between DE miRNA and DE target genes strongly indicated post-transcriptional regulation in the hypoxia inducible factor 1, insulin, and p53 signaling pathways, which might play significant roles in high-altitude acclimatization in domestic goats. It's also worth noting that we experimentally confirmed miR-106a-5p to have a negative regulation effect on angiogenesis by directly targeting FLT-1. These results provide insight into the complicated miRNA expression patterns and regulatory mechanisms of high-altitude acclimatization in domestic goats.

Comparative Transcriptome Analyses of Gayal (Bos frontalis), Yak (Bos grunniens), and Cattle (Bos taurus) Reveal the High-Altitude Adaptation

“…The result indicated that tissue differentiation may precede species differentiation, which was consistent with previous studies ( Necsulea and Kaessmann, 2014 ; Hao et al, 2019 ). However, the samples of heart and muscle from each species were more similar than the same tissue between different species (species-specific expression pattern), which reflects striated muscular tissues may have similar expression profiles ( Merkin et al, 2012 ; Tang et al, 2017 ; Feng et al, 2020 ) ( Figure 1A ). In addition, our expression profiles suggested that the differences in global gene expression among tissues were more significant than that among altitudes or the same tissue of different species, which was consistent with the results of previous studies ( Necsulea and Kaessmann, 2014 ; Tang et al, 2017 ; Hao et al, 2019 ).…”

Comprehensive Analysis of Long Non-coding RNA and mRNA Transcriptomes Related to Hypoxia Adaptation in Tibetan Sheep

“…Studies have shown that high-altitude hypoxic environments have an important impact on energy metabolism in animals ( 15 , 20 , 21 ). Similarly, we found many differentially expressed genes and signaling pathways related to glucose and lipid metabolism.…”

MicroRNAs as Biomarkers for Animal Health and Welfare in Livestock

“…Comparative miRNA transcriptome analysis of two goat populations at distinct altitudes produced reliable evidence for acclimatization based on miRNA-mRNA interactions in hypoxia-related pathways, including that associated with hypoxia inducible factor 1 (HIF-1). The downregulation of miR-509-3p, miR-3069-1-3p, miR-409-5p, and miR-208-3p, and the upregulation of miR-106a-5p, were reported in the hypoxia-sensitive tissues selected by the authors, including the heart, kidney, liver, muscle, and spleen, confirming that miRNAs have a regulatory role in mechanisms related to high-altitude adaptation (115). The potential target genes of these DE-miRNAs are involved in apoptosis, angiogenesis, DNA damage repair, erythropoiesis, and energy metabolism (115).…”

“…The downregulation of miR-509-3p, miR-3069-1-3p, miR-409-5p, and miR-208-3p, and the upregulation of miR-106a-5p, were reported in the hypoxia-sensitive tissues selected by the authors, including the heart, kidney, liver, muscle, and spleen, confirming that miRNAs have a regulatory role in mechanisms related to high-altitude adaptation (115). The potential target genes of these DE-miRNAs are involved in apoptosis, angiogenesis, DNA damage repair, erythropoiesis, and energy metabolism (115). Moreover, the authors demonstrated that miR-106a-5p exerted a negative regulatory effect on angiogenesis by targeting the VEGFR1 (or FLT1) gene, thereby paving the way for further utilization of molecular resources in plateau regions.…”

“…Very recently, some miRNAs were found to be DE under highaltitude hypoxia in both goats and cattle (115). Comparative miRNA transcriptome analysis of two goat populations at distinct altitudes produced reliable evidence for acclimatization based on miRNA-mRNA interactions in hypoxia-related pathways, including that associated with hypoxia inducible factor 1 (HIF-1).…”