Living the high life: High-altitude adaptation

Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Genome biology (Impact Factor: 10.81). 09/2010; 11(9):133. DOI: 10.1186/gb-2010-11-9-133
Source: PubMed


Genome-wide scans demonstrate that genetic variants associated with high-altitude adaptation in Tibetans and Andeans arose independently as a result of convergent adaptation.

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Available from: Laura B Scheinfeldt, Feb 14, 2014
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    • "Intrestingly, three isoforms of PPARs (α,γand δ) were all documented direct downstream of miRs [22], [82], [83]. PPRAα were identified had specific functional variants between highland Tibetan populations and normal [85]. However, although PPRAα is in the Gene Ontology biological process ‘response to hypoxia’, but it is not even in the HIF pathway [84]. "
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    ABSTRACT: The lungs undergo changes that are adaptive for high elevation in certain animal species. In chickens, animals bred at high elevations (e.g., Tibet chickens) are better able to hatch and survive under high-altitude conditions. In addition, lowland chicken breeds undergo physiological effects and suffer greater mortality when they are exposed to hypoxic conditions during embryonic development. Although these physiological effects have been noted, the mechanisms that are responsible for hypoxia-induced changes in lung development and function are not known. Here we have examined the role of a particular microRNA (miRNA) in the regulation of lung development under hypoxic conditions. When chicks were incubated in low oxygen (hypoxia), miR-15a was significantly increased in embryonic lung tissue. The expression level of miR-15a in hypoxic Tibet chicken embryos increased and remained relatively high at embryonic day (E)16-20, whereas in normal chickens, expression increased and peaked at E19-20, at which time the cross-current gas exchange system (CCGS) is developing. Bcl-2 was a translationally repressed target of miR-15a in these chickens. miR-16, a cluster and family member of miR-15a, was detected but did not participate in the posttranscriptional regulation of bcl-2. Around E19, the hypoxia-induced decrease in Bcl-2 protein resulted in apoptosis in the mesenchyme around the migrating tubes, which led to an expansion and migration of the tubes that would become the air capillary network and the CCGS. Thus, interfering with miR-15a expression in lung tissue may be a novel therapeutic strategy for hypoxia insults and altitude adaptation.
    Full-text · Article · Jun 2014 · PLoS ONE
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    • "While various studies have focused on a few select candidate gene regions [1], [4], [5], many genetic loci have probably been targeted by selection in high-altitude populations (see review [6]). In order to evaluate whether our previously reported selection targets [7] are significant in a different Tibetan group [13], we carried out genome-wide SNP-based selection scans in a linguistically distinct population from a different region of the Qinghai-Tibetan Plateau. "
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    ABSTRACT: Recent studies have used a variety of analytical methods to identify genes targeted by selection in high-altitude populations located throughout the Tibetan Plateau. Despite differences in analytic strategies and sample location, hypoxia-related genes, including EPAS1 and EGLN1, were identified in multiple studies. By applying the same analytic methods to genome-wide SNP information used in our previous study of a Tibetan population (n = 31) from the township of Maduo, located in the northeastern corner of the Qinghai-Tibetan Plateau (4200 m), we have identified common targets of natural selection in a second geographically and linguistically distinct Tibetan population (n = 46) in the Tuo Tuo River township (4500 m). Our analyses provide evidence for natural selection based on iHS and XP-EHH signals in both populations at the p<0.02 significance level for EPAS1, EGLN1, HMOX2, and CYP17A1 and for PKLR, HFE, and HBB and HBG2, which have also been reported in other studies. We highlight differences (i.e., stratification and admixture) in the two distinct Tibetan groups examined here and report selection candidate genes common to both groups. These findings should be considered in the prioritization of selection candidate genes in future genetic studies in Tibet.
    Full-text · Article · Mar 2014 · PLoS ONE
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    • "The rationale was that any differences captured in the genetic structure between the two populations are likely to have arisen through natural selection in response to the hypoxic environment inhabited by the Tibetans. These studies have been extensively reviewed (5, 51, 76, 79). The studies are summarized in Table 1, and the key findings are discussed below. "
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    ABSTRACT: The Tibetan Plateau is one of the highest regions on Earth. Tibetan highlanders are adapted to life and reproduction in a hypoxic environment and possess a suite of distinctive physiological traits. Recent studies have identified genomic loci that have undergone natural selection in Tibetans. Two of these loci - EGLN1 and EPAS1 - encode major components of the hypoxia-inducible factor (HIF) transcriptional system, which has a central role in oxygen sensing and coordinating an organism's response to hypoxia, as evidenced by studies in humans and mice. An association between genetic variants within these genes and hemoglobin concentration in Tibetans at high altitude was demonstrated in some of the studies (8, 78, 94). Nevertheless, the functional variants within these genes and the underlying mechanisms of action are still not known. Furthermore, there are a number of other possible phenotypic traits, besides hemoglobin concentration, upon which natural selection may have acted. Integration of studies at the genomic level with functional molecular studies and studies in systems physiology has the potential to provide further understanding of human evolution in response to high-altitude hypoxia. The Tibetan paradigm provides further insight on the role of the HIF system in humans in relation to oxygen homeostasis.
    Full-text · Article · Nov 2013 · Journal of Applied Physiology
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