High-altitude Adaptation Research Articles

High-altitude adaptation: Role of genetic and epigenetic factors

After the completion of the Human Genome Project in 2003, the field of genetics has witnessed massive progress that spanned research in high-altitude biology also. Especially the decade of 2010s witnessed the most of it and revealed various genetic signatures of high-altitude adaptation in Tibetans, Andeans and Ethiopians. High-altitude area, with its extreme environment, harbors a tremendous potential for gene-environment interaction, an aspect that could be explored by epigenetic studies. There are only four original articles till now which explore the epigenetic aspect of high-altitude adaptation or acclimatization. However, there is no comprehensive review to provide complete information on the genetic and epigenetic aspects of high-altitude adaptations. Hence, we have prepared this mini-review to summarize the genetic and epigenetic studies that have correlated the high-altitude adaptation or acclimatization, until recently.

The right ventricle of transplanted hearts at 2,640 meters above sea level. A latin-american experience.

Background:High-altitude cardiovascular adaptations increase lung pressure. This effect on the right ventricle (RV) of transplanted hearts at altitudes above 2,500 meters above sea level (masl) has not been described.Objective:The objective of the study was to describe echocardiography RV behavior in the immediate post-operative period (Days 1-7 post-Heart transplant [HTx]), 3, 6, 12, and 24 months after HTx in patients at 2,640 masl.Methods:Historical cohort of HTx patients in the period between 2005 and 2019, in a hospital located in Bogotá, Colombia. Socio-demographic, clinical, and echocardiographic evaluation data of the RV at 5 follow-up moments were analyzed.Results:91 patients underwent HTx, 64% remained at a height > 2,500 masl in the post-operative period. Transthoracic echo was available in 37 patients (40.6%). Right ventricular dysfunction was found in 95% of patients, which was predominantly moderate (43%), with improvement 3 months after transplant. The immediate post-operative Tricuspid annular plane systolic excursion was 8.9 ± 4.9 mm, with recovery from the 3rd post-operative month (15.1 ± 3.6 mm) and without significant changes in month 24 (15.8 ± 4.9 mm). Immediate post-operative systolic pulmonary artery pressure (sPAP) was 39.2 ± 8.2 mmHg, showing a decrease at 24 post-operative months (31.0 ± 5.0 mmHg). The 5-year survival was 78% Confidence Interval 95% 60-85.Conclusion:After HTx, most patients present right ventricular dysfunction, improving at the 3rd month of transplant. There were no significant differences between patients living at more than 2,500 masl and < 2,500 masl.

Genome-wide CNV analysis reveals variants associated with high-altitude adaptation and meat traits in Qaidam cattle

Qaidam cattle are local breeds that habitats in northwest China. It has many excellent characteristics, such as high cold and roughage tolerance, low oxygen adaptability, and tender meat quality. Copy number variation (CNV) can induce phenotypic changes in animals by a variety of effects, and thus affects the biological functions of the animals. To explore the molecular mechanism of its adaptation to extreme cold weather and muscle fat development, the CNV variations in the genome of three Qaidam cattle were detected by whole-genome sequencing, in this study. A total of 16,743 CNVs and 9498 copy number variable regions (CNVRs) were obtained after the screening, which accounts for 2.18% of the bovine genome. The CNVR length detected ranged from 0.3 KB to 10.77 KB, with a total length of 58.17 MB and an average length of 6.12 KB/ CNVR. Through functional enrichment of CNVR related genes, LDHB, and ME1 genes were screened as the key genes for Qaidam cattle to adapt to the cold and low oxygen environments, whereas KIT and FGF18 genes might be related to the coat color and growth. In the CNVR overlapped with QTLs, variation in CAPN1 and CAST genes might be closely related to the tender meat quality of Qaidam cattle. Therefore, this study provides new genetic insights on the environmental adaptability and important economic traits of Qaidam cattle. How to cite: Guo S, Wu X, Pei J, et al. Genome-wide CNV analysis reveals variants associated with high-altitude adaptation and meat traits in Qaidam cattle. Electron J Biotechnol 2021;54. https://doi.org/10.1016/j.ejbt.2021.07.006

Plant diversity and ecology on the Qinghai–Tibet Plateau

Plant diversity and ecology on the Qinghai–Tibet Plateau

High Altitude Hypoxia

The world's highest and largest altitude area is called the Qinghai-Tibetan plateau QTP, which harbors unique animal and plant species. Mammals that inhabit the higher altitude regions have adapted well to the hypoxic conditions. One of the main stressor at high altitudes is hypoxia. Metabolic responses to hypoxia play important roles in cell survival strategies and some diseases. However, the homeostatic alterations that equilibrate variations in the demand and supply of energy to maintain organismal function in a prolonged low O2 environment persist partly in understood, making it problematic to differentiate adaptive from maladaptive responses in hypoxia. Tibetans and yaks are two perfect examples innate to the plateau for high altitude adaptation. By the scan of the whole-genome, EPAS1 and EGLN1 were identified as key genes associated with sustained hemoglobin concentration in high altitude mammals for adaptation. The yak is a much more ancient mammal that has existed on QTP longer than humans. It is, therefore, possible that natural selection represented a diverse group of genes/pathways in yaks. Physiological characteristics are extremely informative in revealing molecular networks associated with inherited adaptation, in addition to the whole-genome adaptive changes at the DNA sequence level. Gene-expression can be changed by a variety of signals originating from the environment, and hypoxia is the main factor amongst them. The hypoxia-inducible factors (HIF-1α and EPAS1/HIF-2α) are the main regulators of oxygen in homeostasis, which play a role as maestro regulators of adaptation in the hypoxic reaction of molecular mechanisms. The basis of this review is to present recent information regarding the molecular mechanism involved in hypoxia that regulates candidate genes and proteins. Many transcriptional responses toward hypoxia are facilitated by HIFs that change the number of gene expressions and help in angiogenesis, erythropoiesis, metabolic reprogramming, and metastasis. HIFs also activate several signals highlighting a strong association between hypoxia, the misfolded proteins’ accumulation in the endoplasmic reticulum in stress, and activation of Unfolded Protein Response (UPR). It was observed that at high-altitudes, pregnancies yield a low birth weight 100 g per1000 m of the climb. It may involve variation in the events of energy-demand, like protein synthesis. Prolonged hypobaric hypoxia causes placental ER stress, which, in turn, moderates protein synthesis and reduces proliferation. Further, Cardiac hypertrophy by cytosolic Ca2+ raises and Ca2+/calmodulin, calcineurin stimulation, NF-AT3 pathway might be caused by an imbalance in Sarcoplasmic reticulum ER Ca2+, which might be adaptive in the beginning but severe later on.

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

BackgroundYaks 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.ResultsHere, 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.ConclusionsThis 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.

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

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.

Genomic and functional evidence reveals convergent evolution in fishes on the Tibetan Plateau.

High-altitude environments are strong drivers of adaptive evolution in endemic organisms. However, little is known about the genetic mechanisms of convergent adaptation among different lineages, especially in fishes. There are three independent fish groups on the Tibetan Plateau: Tibetan Loaches, Schizothoracine fishes and Glyptosternoid fishes; all are well adapted to the harsh environmental conditions. They represent an excellent example of convergent evolution but with an unclear genetic basis. We used comparative genomic analyses between Tibetan fishes and fishes from low altitudes and detected genomic signatures of convergent evolution in fishes on the Tibetan Plateau. The Tibetan fishes exhibited genome-wide accelerated evolution in comparison with a control set of fishes from low altitudes. A total of 368 positively selected genes were identified in Tibetan fishes, which were enriched in functional categories related to energy metabolism and hypoxia response. Widespread parallel amino acid substitutions were detected among the Tibetan fishes and a subset of these substitutions occurred in positively selected genes associated with high-altitude adaptation. Functional assays suggested that von Hippel-Lindau (VHL) tumour suppressor genes from Tibetan fishes enhance hypoxia-inducible factor (HIF) activity convergently under hypoxia compared to low-altitude fishes. The results provide genomic and functional evidence supporting convergent genetic mechanisms for high-altitude adaptation in fishes on the Tibetan Plateau.

Comparative Genomics Reveals Recent Adaptive Evolution in Himalayan Giant Honeybee Apis laboriosa.

The Himalayan giant honeybee, Apis laboriosa, is the largest individual honeybee with major ecological and economic importance in high-latitude environments. However, our understanding of its environmental adaptations is circumscribed by the paucity of genomic data for this species. Here, we provide a draft genome of wild A. laboriosa, along with a comparison to its closely related species, Apis dorsata. The draft genome of A. laboriosa based on the de novo assembly is 226.1 Mbp in length with a scaffold N50 size of 3.34 Mbp, a GC content of 32.2%, a repeat content of 6.86%, and a gene family number of 8,404. Comparative genomics analysis revealed that the genes in A. laboriosa genome have undergone stronger positive selection (2.5 times more genes) and more recent duplication/loss events (6.1 times more events) than those in the A. dorsata genome. Our study implies the potential molecular mechanisms underlying the high-altitude adaptation of A. laboriosa and will catalyze future comparative studies to understand the environmental adaptation of modern honeybees.

Analysis of selection signatures reveals important insights into the adaptability of high-altitude Indian sheep breed Changthangi.

Changthangi is a high-altitude sheep breed of India that is adapted to cold and hypoxic climate of Himalayas. In the present study, we analysed population structure of Changthangi and contrasted it with selected Indian and European commercial sheep breeds to detect genomic regions under positive selection. The Illumina OvineSNP50v1 genotype data on 292 animals from seven different sheep breeds i.e., Changthangi (n=29), Garole (n=26), Deccani (n=24), Tibetan (n=37), Rambouillet (n=102) and Australian Merino (n=50) was used. European Mouflon (n=24) was used as an out-group for studying the stratification and phylogenetic lineage. While the principal component analysis (PCA) revealed Changthangi to cluster with Tibetan sheep; TREEMIX and ADMIXTURE results also detected the introgression of lowland Indian sheep inheritance in Changthangi. Changthangi sheep were compared with other breed groups as reference i.e., commercial (Australian Merino and Rambouillet), Indian (Deccani, Garole and Tibetan) and breeds inhabiting plains (Australian Merino, Rambouillet, Deccani and Garole). Genomic comparisons of Changthangi using cross population extended haplotype homozygosity (XP-EHH) showed multiple functional regions present on Ovis aries (Oar) chromosomes 2, 3, 6 and 18 to be under selection in Changthangi sheep. These regions were related with adaptation to climatic and hypoxic stressors, fleece characteristics and functioning of immune and reproductive systems. UCP genes, associated with adaptation to cold and hypoxic conditions, were the main loci under positive selection in Changthangi sheep population. The selection signals in Indian and European commercial sheep breeds were mainly associated with body weight and carcass traits. Furthermore, selection signals found in different comparisons were found to be part of different quantitative trait loci (QTLs) associated with important traits in different breed classes. The genes present in these regions are suitable candidates for future studies on the genetic mechanisms underlying high-altitude adaptation.

HLA-G 3’UTR haplotype frequencies in highland and lowland South Native American populations

Human Leukocyte Antigen (HLA)-G participates in several biological processes, including reproduction, vascular remodeling, immune tolerance, and hypoxia response. HLA-G is a potential candidate gene for high altitude adaptation since its expression is modulated in both micro and macro environment under hypoxia and constant cellular stress. Besides the promoter region, the HLA-G 3′untranslated region (UTR) influences HLA-G expression patterns through several post-transcriptional mechanisms. Currently, the 3′UTR genetic diversity in terms of altitude adaptation of Native American populations is still unexplored, particularly at high altitude ecoregions. Here, we evaluated 288 Native Americans from 9 communities located in the Andes [highland (HL); ≥2,500 m (range = 2,838–4,433 m)] and 8 populations located in lowland (LL) regions [<2,500 m (range = 80–431 m); Amazonian tropical forest, Brazilian central plateau, and Chaco] of South America. In total, nine polymorphic sites and ten haplotypes were observed. The most frequent haplotypes (UTR-1, UTR-2, and UTR-3) accounted for ∼ 77% of haplotypes found in LL, while in the HL, the same haplotypes reach ∼ 93%. Also, a remarkable high frequency of putative ancestral UTR-5 haplotype was observed in LL (21.5%), while in HL UTR-2 reaches up to 47%. Further, UTR-2 frequency positively correlates with altitude-related variables, while a negative correlation for UTR-5 was observed. From an evolutionary perspective, we observed a tendency towards balancing selection in HL and LL populations thus suggesting that haplotypes of ancient and more derived alleles may have been co-opted for relatively recent adaptations such as those experienced by modern humans in the highland and lowland of South America. We also discuss how long-term balancing selection can be a reservoir of genetic variants that can be positively selected. Finally, our study provides some pieces of evidence that HLA-G 3′UTR haplotypes may have contributed to high altitude adaptation in the Andes.

De novo Assembly, Annotation, and Analysis of Transcriptome Data of the Ladakh Ground Skink Provide Genetic Information on High-Altitude Adaptation

The Himalayan Arc is recognized as a global biodiversity hotspot. Among its numerous cryptic and undiscovered organisms, this composite high-mountain ecosystem harbors many taxa with adaptations to life in high elevations. However, evolutionary patterns and genomic features have been relatively rarely studied in Himalayan vertebrates. Here, we provide the first well-annotated transcriptome of a Greater Himalayan reptile species, the Ladakh Ground skink Asymblepharus ladacensis (Squamata: Scincidae). Based on tissues from the brain, an embryonic disc, and pooled organ material, using pair-end Illumina NextSeq 500 RNAseq, we assembled ~77,000 transcripts, which were annotated using seven functional databases. We tested ~1600 genes, known to be under positive selection in anurans and reptiles adapted to high elevations, and potentially detected positive selection for 114 of these genes in Asymblepharus. Even though the strength of these results is limited due to the single-animal approach, our transcriptome resource may be valuable data for further studies on squamate reptile evolution in the Himalayas as a hotspot of biodiversity.

Identification of a miRNA–mRNA Regulatory Networks in Placental Tissue Associated With Tibetan High Altitude Adaptation

The Tibetan population has lived and successfully reproduced at high altitude for many generations. Studies have shown that Tibetans have various mechanisms for protection against high-altitude hypoxia, which are probably due, at least in part, to placental adaptation. However, comprehensive in silico analyses of placentas in Tibetans are lacking. We performed a microarray-based comparative transcriptome analysis of 10 Tibetan women from Yushu, Qinghai, CHN (∼3,780 m) and 10 European women living in Leadville, CO, United States (∼3,100 m) for less than three generations. Expression of HIF-1α, STAT3, EGFR, HSP5A, XBP1, and ATF6A mRNA was less in the Tibetan placentas as compared with European placentas. A total of 38 miRNAs were involved in regulating these genes. Differentially expressed genes were enriched for HIF1α signaling pathways, protein processing in the endoplasmic reticulum, PI3K-AKT signaling pathways, and MAPK signaling pathways. Based on the transcriptome profiles, the Tibetan population was distinct from the European population; placental tissues from the Tibetan population are lacking hypoxic responses, and “passivation” occurs in response to hypoxic stress. These results provide insights into the molecular signature of adaptation to high altitudes in these two populations.

Transcriptomes of Saussurea (Asteraceae) Provide Insights into High-Altitude Adaptation.

Understanding how species adapt to extreme environments is an extension of the main goals of evolutionary biology. While alpine plants are an ideal system for investigating the genetic basis of high-altitude adaptation, genomic resources in these species are still limited. In the present study, we generated reference-level transcriptomic data of five Saussurea species through high-throughput sequencing and de novo assembly. Three of them are located in the highland of the Qinghai-Tibet Plateau (QTP), and the other two are close relatives distributed in the lowland. A series of comparative and evolutionary genomics analyses were conducted to explore the genetic signatures of adaptive evolution to high-altitude environments. Estimation of divergence time using single-copy orthologs revealed that Saussurea species diversified during the Miocene, a period with extensive tectonic movement and climatic fluctuation on the QTP. We characterized gene families specific to the alpine species, including genes involved in oxidoreductase activity, pectin catabolic process, lipid transport, and polysaccharide metabolic process, which may play important roles in defense of hypoxia and freezing temperatures of the QTP. Furthermore, in a phylogenetic context with the branch model, we identified hundreds of genes with signatures of positive selection. These genes are involved in DNA repair, membrane transport, response to UV-B and hypoxia, and reproductive processes, as well as some metabolic processes associated with nutrient intake, potentially responsible for Saussurea adaptation to the harsh environments of high altitude. Overall, our study provides valuable genomic resources for alpine species and gained helpful insights into the genomic basis of plants adapting to extreme environments.

Adaptation Mechanisms of Yak (Bos grunniens) to High-Altitude Environmental Stress.

Simple SummaryThe yak is a multipurpose domesticated animal that serves as a protein source for local herders and a sacred carrier of culture and religion. Besides their economic significance, yaks harbor special morphological, physiological, biochemical, and genetic adaptations for tolerance to high-altitude stress. Morphologically, yaks have large hearts and lungs, compact bodies, thick outer hair covering, and nonfunctional sweat glands, which help to withstand hypoxia and cold stress. A reduced heat production, decreased respiration and sweating, reduced metabolism, and efficient nitrogen utilization are the major physiological and biochemical mechanisms for yak survival at high altitudes. Furthermore, the yak has undergone long-term natural selection and developed a unique genetic architecture that favors survival in hostile environments. The yak expresses the HIF-1α pathway-related genes (ADAM17, ARG2, and MMP3) putatively involved in hypoxia response and nutrition pathways genes (CAMK2B, GENT3, HSD17B12, WHSC1, and GLUL) for nutritional assimilation at high altitudes.Living at a high altitude involves many environmental challenges. The combined effects of hypoxia and cold stress impose severe physiological challenges on endothermic animals. The yak is integral to the livelihood of the people occupying the vast, inhospitable Qinghai–Tibetan plateau and the surrounding mountainous region. Due to long-term selection, the yak exhibits stable and unique genetic characteristics which enable physiological, biochemical, and morphological adaptations to a high altitude. Thus, the yak is a representative model for mammalian plateau-adaptability studies. Understanding coping mechanisms provides unique insights into adaptive evolution, thus informing the breeding of domestic yaks. This review provides an overview of genetic adaptations in Bos grunniens to high-altitude environmental stress. Combined genomics and theoretical advances have informed the genetic basis of high-altitude adaptations.

Application of a novel haplotype-based scan for local adaptation to study high-altitude adaptation in rhesus macaques.

When natural populations split and migrate to different environments, they may experience different selection pressures that can lead to local adaptation. To capture the genomic patterns of a local selective sweep, we develop XP‐nSL, a genomic scan for local adaptation that compares haplotype patterns between two populations. We show that XP‐nSL has power to detect ongoing and recently completed hard and soft sweeps, and we then apply this statistic to search for evidence of adaptation to high altitude in rhesus macaques. We analyze the whole genomes of 23 wild rhesus macaques captured at high altitude (mean altitude > 4000 m above sea level) to 22 wild rhesus macaques captured at low altitude (mean altitude < 500 m above sea level) and find evidence of local adaptation in the high‐altitude population at or near 303 known genes and several unannotated regions. We find the strongest signal for adaptation at EGLN1, a classic target for convergent evolution in several species living in low oxygen environments. Furthermore, many of the 303 genes are involved in processes related to hypoxia, regulation of ROS, DNA damage repair, synaptic signaling, and metabolism. These results suggest that, beyond adapting via a beneficial mutation in one single gene, adaptation to high altitude in rhesus macaques is polygenic and spread across numerous important biological systems.

Genomic basis of high-altitude adaptation in Tibetan Prunus fruit trees

The Great Himalayan Mountains and their foothills are believed to be the place of origin and development of many plant species. The genetic basis of adaptation to high plateaus is a fascinating topic that is poorly understood at the population level. We comprehensively collected and sequenced 377 accessions of Prunus germplasm along altitude gradients ranging from 2,067 to 4,492m in the Himalayas. We de novo assembled three high-quality genomes of Tibetan Prunus species. A comparative analysis of Prunus genomes indicated a remarkable expansion of the SINE retrotransposons occurred in the genomes of Tibetan species. We observed genetic differentiation between Tibetan peaches from high and low altitudes and that genes associated with light stress signaling, especially UV stress signaling, were enriched in the differentiated regions. By profiling the metabolomes of Tibetan peach fruit, we determined 379 metabolites had significant genetic correlations with altitudes and that in particular phenylpropanoids were positively correlated with altitudes. We identified 62 Tibetan peach-specific SINEs that colocalized with metabolites differentially accumualted in Tibetan relative to cultivated peach. We demonstrated that two SINEs were inserted in a locus controlling the accumulation of 3-O-feruloyl quinic acid. SINE1 was specific to Tibetan peach. SINE2 was predominant in high altitudes and associated with the accumulation of 3-O-feruloyl quinic acid. These genomic and metabolic data for Prunus populations native to the Himalayan region indicate that the expansion of SINE retrotransposons helped Tibetan Prunus species adapt to the harsh environment of the Himalayan plateau by promoting the accumulation of beneficial metabolites.

Genomic analysis of field pennycress (Thlaspi arvense) provides insights into mechanisms of adaptation to high elevation

BackgroundUnderstanding how organisms evolve and adapt to extreme habitats is of crucial importance in evolutionary ecology. Altitude gradients are an important determinant of the distribution pattern and range of organisms due to distinct climate conditions at different altitudes. High-altitude regions often provide extreme environments including low temperature and oxygen concentration, poor soil, and strong levels of ultraviolet radiation, leading to very few plant species being able to populate elevation ranges greater than 4000 m. Field pennycress (Thlaspi arvense) is a valuable oilseed crop and emerging model plant distributed across an elevation range of nearly 4500 m. Here, we generate an improved genome assembly to understand how this species adapts to such different environments.ResultsWe sequenced and assembled de novo the chromosome-level pennycress genome of 527.3 Mb encoding 31,596 genes. Phylogenomic analyses based on 2495 single-copy genes revealed that pennycress is closely related to Eutrema salsugineum (estimated divergence 14.32–18.58 Mya), and both species form a sister clade to Schrenkiella parvula and genus Brassica. Field pennycress contains the highest percentage (70.19%) of transposable elements in all reported genomes of Brassicaceae, with the retrotransposon proliferation in the Middle Pleistocene being likely responsible for the expansion of genome size. Moreover, our analysis of 40 field pennycress samples in two high- and two low-elevation populations detected 1,256,971 high-quality single nucleotide polymorphisms. Using three complementary selection tests, we detected 130 candidate naturally selected genes in the Qinghai-Tibet Plateau (QTP) populations, some of which are involved in DNA repair and the ubiquitin system and potential candidates involved in high-altitude adaptation. Notably, we detected a single base mutation causing loss-of-function of the FLOWERING LOCUS C protein, responsible for the transition to early flowering in high-elevation populations.ConclusionsOur results provide a genome-wide perspective of how plants adapt to distinct environmental conditions across extreme elevation differences and the potential for further follow-up research with extensive data from additional populations and species.

Enhanced Placental Mitochondrial Respiration in Tibetan Women at High Altitude.

Living at high altitudes is extremely challenging as it entails exposure to hypoxia, low temperatures, and high levels of UV radiation. However, the Tibetan population has adapted to such conditions on both a physiological and genetic level over 30,000–40,000 years. It has long been speculated that fetal growth restriction is caused by abnormal placental development. We previously demonstrated that placentas from high-altitude Tibetans were protected from oxidative stress induced by labor compared to those of European descent. However, little is known about how placental mitochondria change during high-altitude adaptation. In this study, we aimed to uncover the mechanism of such adaptation by studying the respiratory function of the placental mitochondria of high-altitude Tibetans, lower-altitude Tibetans, and lower-altitude Chinese Han. We discovered that mitochondrial respiration was greater in high-altitude than in lower-altitude Tibetans in terms of OXPHOS via complexes I and I+II, ETSmax capacity, and non-phosphorylating respiration, whereas non-ETS respiration, LEAK/ETS, and OXPHOS via complex IV did not differ. Respiration in lower-altitude Tibetans and Han was similar for all tested respiratory states. Placentas from high-altitude Tibetan women were protected from acute ischemic/hypoxic insult induced by labor, and increased mitochondrial respiration may represent an acute response that induces mitochondrial adaptations.

Fetal growth, high altitude, and evolutionary adaptation: a new perspective.

Residence at high altitude is consistently associated with low birthweight among placental mammals. This reduction in birthweight influences long-term health trajectories for both the offspring and mother. However, the physiological processes that contribute to fetal growth restriction at altitude are still poorly understood, and thus our ability to safely intervene remains limited. One approach to identify the factors that mitigate altitude-dependent fetal growth restriction is to study populations that are protected from fetal growth restriction through evolutionary adaptations (e.g., high altitude-adapted populations). Here, we examine human gestational physiology at high altitude from a novel evolutionary perspective that focuses on patterns of physiological plasticity, allowing us to identify 1) the contribution of specific physiological systems to fetal growth restriction and 2) the mechanisms that confer protection in highland-adapted populations. Using this perspective, our review highlights two general findings: first, that the beneficial value of plasticity in maternal physiology is often dependent on factors more proximate to the fetus; and second, that our ability to understand the contributions of these proximate factors is currently limited by thin data from altitude-adapted populations. Expanding the comparative scope of studies on gestational physiology at high altitude and integrating studies of both maternal and fetal physiology are needed to clarify the mechanisms by which physiological responses to altitude contribute to fetal growth outcomes. The relevance of these questions to clinical, agricultural, and basic research combined with the breadth of the unknown highlight gestational physiology at high altitude as an exciting niche for continued work.