scholarly journals Selection Signatures Analysis Reveals Genes Associated with High-Altitude Adaptation in Tibetan Goats from Nagqu, Tibet

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1599
Author(s):  
Meilin Jin ◽  
Jian Lu ◽  
Xiaojuan Fei ◽  
Zengkui Lu ◽  
Kai Quan ◽  
...  
Keyword(s):  
High Altitude ◽  
Growth Factor Signaling ◽  
Vascular Endothelial ◽  
Model Based Clustering ◽  
Adverse Conditions ◽  
High Altitude Adaptation ◽  
Significant Difference ◽  
Altitude Adaptation ◽  
Endothelial Growth Factor

Tibetan goat is an ancient breed, which inhabits the adverse conditions of the plateaus in China. To investigate the role of selection in shaping its genomes, we genotyped Tibetan goats (Nagqu Prefecture, above 4500 m) and three lowland populations (Xinjiang goats, Taihang goats and Huanghuai goats). The result of PCA, neighbor-joining (N-J) tree and model-based clustering showed that the genetic structure between the Tibetan goat and the three lowland populations has significant difference. As demonstrated by the di statistic, we found that some genes were related to the high-altitude adaptation of Tibetan goats. Functional analysis revealed that these genes were enriched in the VEGF (vascular endothelial growth factor) signaling pathway and melanoma, suggesting that nine genes (FGF2, EGFR, AKT1, PTEN, MITF, ENPEP, SIRT6, KDR, and CDC42) might have important roles in the high-altitude adaptation of Nagqu Tibetan goats. We also found that the LEPR gene was under the strongest selection (di value = 16.70), and it could induce upregulation of the hypoxic ventilatory response. In addition, five genes (LEPR, LDB1, EGFR, NOX4 and FGF2) with high di values were analyzed using q-PCR. Among them, we found that LEPR, LDB1 and FGF2 exhibited higher expression in the lungs of the Tibetan goats; LEPR, EGFR and LDB1 exhibited higher expression in the hearts of the Huanghuai goat. Our results suggest that LEPR, LDB1, EGFR and FGF2 genes may be related to the high-altitude adaptation of the goats. These findings improve our understanding of the selection of the high-altitude adaptability of the Nagqu Tibetan goats and provide new theoretical knowledge for the conservation and utilization of germplasm resources.

scholarly journals Role of Vascular Endothelial Growth Factor Signaling in Schistosoma-Induced Experimental Pulmonary Hypertension

2014 ◽  
Vol 4 (2) ◽  
pp. 289-299 ◽  
Author(s):  
Jacob J. Chabon ◽  
Liya Gebreab ◽  
Rahul Kumar ◽  
Elias Debella ◽  
Takeshi Tanaka ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Pulmonary Hypertension ◽  
Growth Factor ◽  
Growth Factor Signaling ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

scholarly journals Analysis of human mitochondrial genome co-occurrence networks of Asian population at varying altitudes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rahul K. Verma ◽  
Alena Kalyakulina ◽  
Cristina Giuliani ◽  
Pramod Shinde ◽  
Ajay Deep Kachhvah ◽  
...  
Keyword(s):  
Mitochondrial Genome ◽  
High Altitude ◽  
Dna Sequences ◽  
Large Scale ◽  
Framework Analysis ◽  
Mt Dna ◽  
High Altitude Adaptation ◽  
Altitude Adaptation ◽  
The Impact

AbstractNetworks have been established as an extremely powerful framework to understand and predict the behavior of many large-scale complex systems. We studied network motifs, the basic structural elements of networks, to describe the possible role of co-occurrence of genomic variations behind high altitude adaptation in the Asian human population. Mitochondrial DNA (mtDNA) variations have been acclaimed as one of the key players in understanding the biological mechanisms behind adaptation to extreme conditions. To explore the cumulative effects of variations in the mitochondrial genome with the variation in the altitude, we investigated human mt-DNA sequences from the NCBI database at different altitudes under the co-occurrence motifs framework. Analysis of the co-occurrence motifs using similarity clustering revealed a clear distinction between lower and higher altitude regions. 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 ‘RSRS50’ variant 10,398 was found to co-occur only at higher altitudes supporting the fact that a separate route of colonization at these altitudes might have taken place. Overall, our analysis revealed the presence of co-occurrence interactions specific to high altitude at a whole mitochondrial genome level. This study, combined with the classical haplogroups analysis is useful in understanding the role of co-occurrence of mitochondrial variations in high altitude adaptation.

scholarly journals Role of mitochondrial genetic interactions in determining adaptation to high altitude in human population around the globe

2021 ◽  
Author(s):  
Rahul K Verma ◽  
Alena Kalyakulina ◽  
Ankit Mishra ◽  
Mikhail Ivanchenko ◽  
Sarika Jalan
Keyword(s):  
High Altitude ◽  
Human Population ◽  
Nadh Dehydrogenase ◽  
Gene Interaction ◽  
Genetic Networks ◽  
Genetic Interactions ◽  
High Altitude Adaptation ◽  
Evolutionary Forces ◽  
Altitude Adaptation

Physiological and haplogroup studies performed to understand high-altitude adaptation in humans are limited to individual genes and polymorphic sites. Due to stochastic evolutionary forces, the frequency of a polymorphism is affected by changes in the frequency of a nearby polymorphism on the same DNA sample making them connected in terms of evolution. Here, first, we provide a method to model these mitochondrial polymorphisms as 'co-mutation networks' for three high-altitude populations, Tibetan, Ethiopian and Andean. Then, by transforming these co-mutation networks into weighted and undirected gene-gene interaction (GGI) networks, we were able to identify functionally enriched genetic interactions ofCYBandCO3genes in Tibetan and Andean populations, while NADH dehydrogenase genes in the Ethiopian population playing a significant role in high altitude adaptation. These co-mutation-based genetic networks provide insights into the role of different sets of genes in high-altitude adaptation human sub-populations.

Vascular endothelial growth factor in patients with high-altitude pulmonary edema

2003 ◽  
Vol 94 (5) ◽  
pp. 1836-1840 ◽  
Author(s):  
Masayuki Hanaoka ◽  
Yunden Droma ◽  
Atsuhiko Naramoto ◽  
Takayuki Honda ◽  
Toshio Kobayashi ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Pulmonary Edema ◽  
High Altitude ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Repair Process ◽  
Vascular Endothelial ◽  
High Altitude Pulmonary Edema ◽  
Endothelial Growth Factor

To examine the role of VEGF in the pathogenesis of high-altitude pulmonary edema (HAPE), we measured the concentrations of VEGF in venous serum and bronchoalveolar lavage fluid in patients with HAPE and in healthy volunteers. The VEGF in venous serum of the patients was normal at admission and significantly increased at recovery. Similarly, the VEGF in bronchoalveolar lavage fluid of the patients was increased at recovery compared with admission, but values at both admission and recovery were significantly lower than those of the controls. The present finding suggests that VEGF probably is destroyed in the lung of HAPE, and it appears less likely to have a critical part in the pathogenesis of HAPE but has rather an important role in the repair process for the impaired cell layer.

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