scholarly journals Convergent genomic signatures of high-altitude adaptation among domestic mammals

2019 ◽  
Vol 7 (6) ◽  
pp. 952-963 ◽  
Author(s):  
Dong-Dong Wu ◽  
Cui-Ping Yang ◽  
Ming-Shan Wang ◽  
Kun-Zhe Dong ◽  
Da-Wei Yan ◽  
...  
Keyword(s):  
Positive Selection ◽  
High Altitude ◽  
Adaptive Evolution ◽  
The Tibetan Plateau ◽  
Genomic Signatures ◽  
Gene Level ◽  
Genetic Mechanisms ◽  
Altitude Adaptation ◽  
Insight Into ◽  
Molecular Convergence

Abstract Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we used 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularly the EPAS1 gene in these Tibetan domestic mammals. We also reported a potential function in response to hypoxia for the gene C10orf67, which underwent positive selection in three of the domestic mammals. Our data provide an insight into adaptive evolution of high-altitude domestic mammals, and should facilitate the search for additional novel genes involved in the hypoxia response pathway.

scholarly journals Convergent genomic signatures of high altitude adaptation among domestic mammals

2019 ◽  
Author(s):  
Dong-Dong Wu ◽  
Cui-Ping Yang ◽  
Ming-Shan Wang ◽  
Kun-Zhe Dong ◽  
Da-Wei Yan ◽  
...  
Keyword(s):  
Positive Selection ◽  
High Altitude ◽  
Adaptive Evolution ◽  
The Tibetan Plateau ◽  
Genomic Signatures ◽  
Gene Level ◽  
Genetic Mechanisms ◽  
Altitude Adaptation ◽  
Insight Into ◽  
Molecular Convergence

AbstractAbundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we utilized 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularly EPAS1 gene in these Tibetan domestic mammals. We also reported a potential function in response to hypoxia for the gene C10orf67, which underwent positive selection in three of the domestic mammals. Our data provides insight into adaptive evolution of high-altitude domestic mammals, and should facilitate the search for additional novel genes involved in the hypoxia response pathway.

scholarly journals A comparative analysis of differentially expressed mRNAs, miRNAs and circRNAs provides insights into the key genes involved in the high-altitude adaptation of yaks

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Qianyun Ge ◽  
Yongbo Guo ◽  
Wangshan Zheng ◽  
Yuan Cai ◽  
Xuebin Qi ◽  
...  
Keyword(s):  
High Altitude ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Differentially Expressed ◽  
The Tibetan Plateau ◽  
The Core ◽  
Processing Pathways ◽  
Genetic Information Processing ◽  
Altitude Adaptation ◽  
The Difference

Abstract Background Yaks that inhabit the Tibetan Plateau exhibit striking phenotypic and physiological differences from cattle and have adapted well to the extreme conditions on the plateau. However, the mechanisms used by these animals for the regulation of gene expression at high altitude are not fully understood. Results Here, we sequenced nine lung transcriptomes of yaks at altitudes of 3400, 4200 and 5000 m, and low-altitude Zaosheng cattle, which is a closely related species, served as controls. The analysis identified 21,764 mRNAs, 1377 circRNAs and 1209 miRNAs. By comparing yaks and cattle, 4975 mRNAs, 252 circRNAs and 75 miRNAs were identified differentially expressed. By comparing yaks at different altitudes, we identified 756 mRNAs, 64 circRNAs and 83 miRNAs that were differentially expressed (fold change ≥2 and P-value < 0.05). The pathways enriched in the mRNAs, circRNAs and miRNAs identified from the comparison of yaks and cattle were mainly associated with metabolism, including ‘glycosaminoglycan degradation’, ‘pentose and glucuronate interconversions’ and ‘flavone and flavonol biosynthesis’, and the mRNAs, circRNAs and miRNAs identified from the comparison of yaks at different altitude gradients were significantly enriched in metabolic pathways and immune and genetic information processing pathways. The core RNAs were identified from the mRNA-miRNA-circRNA networks constructed using the predominant differentially expressed RNAs. The core genes specific to the difference between yaks and cattle were associated with the endoplasmic reticulum and fat deposition, but those identified from the comparison among yaks at different altitude gradients were associated with maintenance of the normal biological functions of cells. Conclusions This study enhances our understanding of the molecular mechanisms involved in hypoxic adaptation in yaks and might contribute to improvements in the understanding and prevention of hypoxia-related diseases.

scholarly journals The Expression Regulatory Network in the Lung Tissue of Tibetan Pigs Provides Insight Into Hypoxia-Sensitive Pathways in High-Altitude Hypoxia

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanan Yang ◽  
Haonan Yuan ◽  
Tianliang Yang ◽  
Yongqing Li ◽  
Caixia Gao ◽  
...  
Keyword(s):  
High Altitude ◽  
Regulatory Networks ◽  
Alveolar Wall ◽  
Potential Candidate ◽  
Low Oxygen ◽  
Structure Damage ◽  
High Altitude Adaptation ◽  
Tibetan Pigs ◽  
Altitude Adaptation ◽  
Insight Into

To adapt to a low-oxygen environment, Tibetan pigs have developed a series of unique characteristics and can transport oxygen more effectively; however, the regulation of the associated processes in high-altitude animals remains elusive. We performed mRNA-seq and miRNA-seq, and we constructed coexpression regulatory networks of the lung tissues of Tibetan and Landrace pigs. HBB, AGT, COL1A2, and EPHX1 were identified as major regulators of hypoxia-induced genes that regulate blood pressure and circulation, and they were enriched in pathways related to signal transduction and angiogenesis, such as HIF-1, PI3K-Akt, mTOR, and AMPK. HBB may promote the combination of hemoglobin and oxygen as well as angiogenesis for high-altitude adaptation in Tibetan pigs. The expression of MMP2 showed a similar tendency of alveolar septum thickness among the four groups. These results indicated that MMP2 activity may lead to widening of the alveolar wall and septum, alveolar structure damage, and collapse of alveolar space with remarkable fibrosis. These findings provide a perspective on hypoxia-adaptive genes in the lungs in addition to insights into potential candidate genes in Tibetan pigs for further research in the field of high-altitude adaptation.

scholarly journals Altitude-wise analysis of co-occurrence networks of mitochondrial genome in Asian population

2019 ◽  
Author(s):  
Rahul K Verma ◽  
Cristina Giuliani ◽  
Alena Kalyakuina ◽  
Ajay Deep Kachhvah ◽  
Mikhail Ivanchenko ◽  
...  
Keyword(s):  
Mitochondrial Genome ◽  
High Altitude ◽  
Dna Sequences ◽  
Group Analysis ◽  
Asian Population ◽  
The Tibetan Plateau ◽  
Mt Dna ◽  
High Altitude Adaptation ◽  
Altitude Adaptation ◽  
The Impact

ABSTRACTFinding mechanisms behind high altitude adaptation in humans at the Tibetan plateau has been a subject of evolutionary research. Mitochondrial DNA (mt-DNA) variations have been established as one of the key players in understanding the biological mechanisms at the basis of adaptation to these extreme conditions. To explore cumulative effects and dynamics of the variations in mitochondrial genome at varying altitudes, we investigated human mt-DNA sequences from NCBI database at different altitudes by employing co-occurrence motifs framework. We constructed co-occurrence motifs by taking into account variable sites for each altitude group. Analysis of the co-occurrence motifs using similarity clustering revealed a clear distinction between a lower and a higher altitude region. In addition, the previously known high altitude markers 3394 and 7697 (which are definitive sites of haplogroup M9a1a1c1b) were found to co-occur within their own gene complexes indicating the impact of intra-genic constraint on co-evolution of nucleotides. Furthermore, an ancestral marker 10398 was found to co-occur only at higher altitudes supporting the fact that a separate root of colonization at these altitudes might have taken place. Overall, our analysis revealed the presence of co-occurrence motifs at a whole mitochondrial genome level. This study, combined with the classical haplogroups analysis is useful in understanding role of co-occurrence of mitochondrial variations in high altitude adaptation.

scholarly journals Identifying positive selection candidate loci for high-altitude adaptation in Andean populations

2009 ◽  
Vol 4 (2) ◽  
Author(s):  
Abigail W. Bigham ◽  
Xianyun Mao ◽  
Rui Mei ◽  
Tom Brutsaert ◽  
Megan J. Wilson ◽  
...  
Keyword(s):  
Positive Selection ◽  
High Altitude ◽  
Selection Candidate ◽  
High Altitude Adaptation ◽  
Altitude Adaptation ◽  
Candidate Loci

scholarly journals Genetic signatures of high-altitude adaptation in Tibetans

2017 ◽  
Vol 114 (16) ◽  
pp. 4189-4194 ◽  
Author(s):  
Jian Yang ◽  
Zi-Bing Jin ◽  
Jie Chen ◽  
Xiu-Feng Huang ◽  
Xiao-Man Li ◽  
...  
Keyword(s):  
High Altitude ◽  
Methylenetetrahydrofolate Reductase ◽  
The Tibetan Plateau ◽  
High Altitude Adaptation ◽  
Drift Model ◽  
Genome Wide ◽  
A Genome ◽  
Altitude Adaptation ◽  
Genetic Signatures ◽  
Genome Wide Study

Indigenous Tibetan people have lived on the Tibetan Plateau for millennia. There is a long-standing question about the genetic basis of high-altitude adaptation in Tibetans. We conduct a genome-wide study of 7.3 million genotyped and imputed SNPs of 3,008 Tibetans and 7,287 non-Tibetan individuals of Eastern Asian ancestry. Using this large dataset, we detect signals of high-altitude adaptation at nine genomic loci, of which seven are unique. The alleles under natural selection at two of these loci [methylenetetrahydrofolate reductase (MTHFR) and EPAS1] are strongly associated with blood-related phenotypes, such as hemoglobin, homocysteine, and folate in Tibetans. The folate-increasing allele of rs1801133 at the MTHFR locus has an increased frequency in Tibetans more than expected under a drift model, which is probably a consequence of adaptation to high UV radiation. These findings provide important insights into understanding the genomic consequences of high-altitude adaptation in Tibetans.

scholarly journals High altitude adaptation mitigates anemia risk associated with diabetes among the Mosuo of Southwest China

2018 ◽  
Author(s):  
M Su ◽  
K Wander ◽  
MK Shenk ◽  
T Blumenfield ◽  
H Li ◽  
...  
Keyword(s):  
Tibetan Plateau ◽  
High Altitude ◽  
Market Integration ◽  
Hypoxia Inducible Factor ◽  
Human Populations ◽  
The Tibetan Plateau ◽  
Low Oxygen ◽  
High Altitude Adaptation ◽  
Altitude Adaptation ◽  
Hb Concentration

AbstractHuman populations native to high altitude regions (≥2500 m) exhibit numerous adaptations to hypoxic stress. On the Tibetan Plateau, these include modifications of the hypoxia inducible factor (HIF) pathway to essentially uncouple erythropoiesis (red blood cell production) and blood hemoglobin (Hb) concentration—which normally increase in response to low oxygen—from hypoxia. Uncoupling of erythropoiesis and hypoxia is also observed among people with diabetes due to damage to kidney tissues. This is hypothesized to result in elevated risk for anemia among diabetics, which increases risk for cardiovascular disease and death. We tested the hypothesis that the independence of erythropoiesis from HIF among high-altitude adapted populations of the Tibetan Plateau may protect against diabetes-associated anemia. We investigated this hypothesis among the Mosuo, a population living in Yunnan Province, China (at ~2800 m altitude) that is undergoing rapid market integration and lifestyle change, with concomitant increase in risk for type 2 diabetes. We found that, although diabetes (glycated hemoglobin, HbA1c ≥6.5%) is associated with anemia (females: Hb<12g/dl; males: Hb<13g/dl) among the Chinese population as a whole (N: 5,606; OR: 1.48; p: 0.008), this is not the case among the Mosuo (N: 316; OR: 1.36; p: 0.532). Both pathways uncoupling hypoxia from erythropoiesis (diabetic disease and high altitude adaptation) are incompletely understood; their intersection in protecting Mosuo with diabetes from anemia may provide insight into the mechanisms underlying each. Further, these findings point to the importance of understanding how high-altitude adaptations interact with chronic disease processes, as populations like the Mosuo experience rapid market integration.

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