Low-altitude Populations Research Articles

Evaluation of the hemoglobin cutoff point for anemia in adult women residents of different altitudinal levels in Peru.

Anemia prevalence is high in countries where high proportion of the population lives at high altitude (HA) due perhaps to the unsuitability hemoglobin correction factor proposed by the WHO. The present study has been designed to evaluate a new approach to establish thresholds of hemoglobin (Hb) when defining anemia at HA. Cross-sectional study evaluating 217 women aged 18 to 75 years-old, residents of 2 cities at low altitude (LA) (130 and 150 meters) and 2 at HA (3800 and 4300 meters). Hb, pulse oxygen saturation (SpO2), arterial oxygen content (CaO2), and inflammatory markers were measured. Three definitions of anemia diagnoses were used: uncorrected Hb, WHO-corrected Hb, and Silubonde's criteria based on ferritin as a gold standard. STATA v18.0 was use for data analysis, p<0.05 indicated significant difference. HA residents present higher Hb values than at LA. Likewise, the highest area under the curve (AUC) ROC (Receiver Operating Characteristic) was observed for uncorrected Hb (AUC = 0.8595; CI95% 0.858-0.86) for the diagnosis of anemia using serum ferritin as the gold standard. Anemia prevalence was higher when using WHO-corrected Hb, 27%, and Silubonde's criteria, 41% (Hb cut-off of 11.10, 12.73, 15.80 and 16.60 g/dl for altitudes of 130, 150, 3800 and 4300 meters, respectively), than using uncorrected Hb to define anemia (7.7%). Serum Ferritin and CaO2 values are lower only in the group with anemia defined with uncorrected Hb than in the groups of anemia using the WHO-corrected Hb or the Silubonde´s criteria. The correction factor of hemoglobin for altitude of residence overestimates the prevalence of anemia in adult women. Likewise, CaO2 could be a potential marker to determine the transport of oxygen in LA and HA populations. Further studies in adult men are required to confirm the present findings.

Death Risk Response of High-Altitude Resident Populations to COVID-19 Vaccine: A Retrospective Cohort Study.

Vásquez-Velásquez, Cinthya, Diego Fano-Sizgorich, and Gustavo F Gonzales. Death risk response of high-altitude resident populations to COVID-19 vaccine: Retrospective cohort study. High Alt Med Biol. 00:00-00, 2024. Background: Peru had one of the highest mortality rates caused by the coronavirus disease 2019 (COVID-19) pandemic worldwide. Vaccination significantly reduces mortality. However, the effectiveness of vaccination might differ at different altitudinal levels. The study aimed to evaluate the effect modification of altitude on the association between vaccination and COVID-19 mortality in Peru. Methodology: A retrospective cohort, using open access databases of deaths, COVID-19 cases, hospitalizations, and vaccination was obtained from the Peruvian Ministry of Health. Deaths due to COVID-19 were evaluated in vaccinated and nonvaccinated patients. Crude (RR) and adjusted relative risks (aRR) were calculated using generalized linear models of Poisson family with robust variances. Models were adjusted for age, sex, pandemic wave, and Human Development Index. To evaluate the interaction by altitude, a stratified analysis by this variable was performed. The variable altitude was categorized as, 0-499 m (828,298 cases), 500-1,499 m (64,735 cases), 1,500-2,499 m (106,572 cases), and ≥2,500 m (179,004 cases). The final sample studied included 1,362,350 cases. Results: The vaccine showed a considerable reduction of death risk with the second (aRR: 0.41, 95% confidence interval [CI]: 0.38-0.44) and third doses (aRR: 0.21, 95% CI: 0.20-0.23). In the adjusted and interaction model, it can be observed that medium and high altitude present a higher risk of death compared to sea level (aRR: 2.58 and 2.03, respectively). Likewise, the two doses' group presents an aRR:1.22 for medium altitude (1,500-2,499 m) and 1.6 for high altitude (≥2,500 m), compared with low-altitude population, suggesting that the action of vaccination at high altitude is altered by the effect of the altitude itself. Conclusions: Altitude might modify the protective effect of SARS-CoV-2 vaccine against COVID-19 death.

Short-term changes in chest CT images among individuals at low altitude after entering high-altitude environments.

To investigate the short-term changes in chest CT images of low-altitude populations after entering a high-altitude environment. Chest CT images of 3,587 people from low-altitude areas were obtained within one month of entering a high-altitude environment. Abnormal CT features and clinical symptoms were analyzed. Besides acute high-altitude pulmonary edema, the incidence of soft tissue space pneumatosis was significantly higher than that in low-altitude areas. Pneumatosis was observed in the mediastinum, cervical muscle space, abdominal cavity, and spinal cord epidural space, especially the mediastinum. In addition to acute high-altitude pulmonary edema, spontaneous mediastinal emphysema often occurs when individuals in low-altitude areas adapt to the high-altitude environment of cold, low-pressure, and hypoxia. When the gas escapes to the abdominal cavity, it is easy to be misdiagnosed as gastrointestinal perforation. It is also not uncommon for gas accumulation to escape into the epidural space of the spinal cord. The phenomenon of gas diffusion into distant tissue space and the mechanism of gas escape needs to be further studied.

Comparative Anatomy of the Respiratory Systems in High Altitude vs. Low Altitude Populations

Comparative Anatomy of the Respiratory Systems in High Altitude vs. Low Altitude Populations

Convergent High O2 Affinity but Distinct ATP-Mediated Allosteric Regulation of Hemoglobins in Oviparous and Viviparous Eremias Lizards from the Qinghai-Tibet Plateau.

The functional adaptation and underlying molecular mechanisms of hemoglobins (Hbs) have primarily concentrated on mammals and birds, with few reports on reptiles. This study aimed to investigate the convergent and species-specific high-altitude adaptation mechanisms of Hbs in two Eremias lizards from the Qinghai-Tibet Plateau. The Hbs of high-altitude E. argus and E. multiocellata were characterized by significantly high overall and intrinsic Hb-O2 affinity compared to their low-altitude populations. Despite the similarly low Cl- sensitivities, the Hbs of high-altitude E. argus exhibited higher ATP sensitivity and ATP-dependent Bohr effects than that of E. multiocellata, which could facilitate O2 unloading in respiring tissues. Eremias lizards Hbs exhibited similarly low temperature sensitivities and relatively high Bohr effects at lower temperatures, which could help to stably deliver and release O2 to cold extremities at low temperatures. The oxygenation properties of Hbs in high-altitude populations might be attributed to varying ratios of β2/β1 globin and substitutions on the β2-type globin. Notably, the Asn12Ala in lowland E. argus could cause localized destabilization of the E-helix in the tetrameric Hb by elimination of hydrogen bonds, thereby resulting in its lowest O2 affinity. This study provides a valuable reference for the high-altitude adaptation mechanisms of hemoglobins in reptiles.

Linking red blood cell functional phenotypes to environmental tolerance in high-altitude adapted deer mice

Oxygen (O2) is essential for vertebrate life, and complex cardio-respiratory systems have evolved to transport the gas from the environment to each individual cell. Even short disruptions of this O2 flux can have deleterious effects that are linked to numerous disease states. Animals that have adapted to hypoxic environments, such as deer mice ( Peromyscus maniculatus) native to high altitude, can provide valuable insight into naturally evolved solutions to O2 deprivation. Previous work has shown that high-altitude deer mice have evolved a higher hemoglobin O2 affnity and other coordinated changes across the O2 transport cascade that enable higher metabolic rates in hypoxia. Red blood cells (RBC) are the functional unit of O2 and carbon dioxide transport in the blood and play central roles in matching O2 supply and demand in the microcirculation by releasing signaling molecules such as ATP and gasotransmitters; but how these cellular mechanisms respond to hypoxic environments has not been studied. We hypothesized that high-altitude adaptation in deer mice has improved the function of RBCs for cardiovascular gas transport in hypoxia. Lab-raised breeding colonies of deer-mice were established from wild mice caught at low altitude (~400 m in the Great Plains of Nebraska) and at high altitude (~4300 m in the Rocky Mountains of Colorado). Using a common-garden experimental design, third-generation deer mice from high- and low-altitude populations were acclimated to warm normoxia (21°C, 21 kPa O2) or cold hypobaric hypoxia (5°C, 12 kPa O2) for 8 weeks. Blood samples were collected for measurements of hematocrit, hemoglobin concentration, RBC volume, plasma erythropoietin concentration, RBC contents of membrane transport and channel proteins (anion exchanger, aquaporin 1 and rhesus associated glycoprotein) by immunocytochemistry and western blotting, and carbonic anhydrase activity using biochemical techniques. The release of ATP from RBCs was measured in tonometers at decreasing levels of O2 by luminometry, and the vascular sensitivity to ATP was determined by wire myography on second-order mesenteric arteries. Finally, bone marrow samples were collected from the femurs to measure gene expression levels in the erythropoietic tissue. Our experimental design allowed us to examine the interactive effects of cold hypoxic environments on RBC phenotype, by untangling environmentally-induced plasticity from the signatures of adaptation that are unique to high-altitude natives. This work is providing a better understanding of how RBC function participates in matching cardiovascular O2 supply and demand in extreme hypoxia, which has important applications in animal and human health. This work was supported by a NSERC Canada Banting Postdoctoral Fellowship to TSH and a Discovery Grant to GRS. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Evolved changes in phenotype across skeletal muscles in deer mice native to high altitude.

The cold and hypoxic conditions at high altitude necessitate high metabolic O2 demands to support thermogenesis while hypoxia reduces O2 availability. Skeletal muscles play key roles in thermogenesis, but our appreciation of muscle plasticity and adaptation at high altitude has been hindered by past emphasis on only a small number of muscles. We examined this issue in deer mice (Peromyscus maniculatus). Mice derived from both high-altitude and low-altitude populations were born and raised in captivity and then acclimated as adults to normoxia or hypobaric hypoxia (12 kPa O2 for 6-8 wk). Maximal activities of citrate synthase (CS), cytochrome c oxidase (COX), β-hydroxyacyl-CoA dehydrogenase (HOAD), hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) were measured in 20 muscles involved in shivering, locomotion, body posture, ventilation, and mastication. Principal components analysis revealed an overall difference in muscle phenotype between populations but no effect of hypoxia acclimation. High-altitude mice had greater activities of mitochondrial enzymes and/or lower activities of PK or LDH across many (but not all) respiratory, limb, core and mastication muscles compared with low-altitude mice. In contrast, chronic hypoxia had very few effects across muscles. Further examination of CS in the gastrocnemius showed that population differences in enzyme activity stemmed from differences in protein abundance and mRNA expression but not from population differences in CS amino acid sequence. Overall, our results suggest that evolved increases in oxidative capacity across many skeletal muscles, at least partially driven by differences in transcriptional regulation, may contribute to high-altitude adaptation in deer mice.NEW & NOTEWORTHY Most previous studies of muscle plasticity and adaptation in high-altitude environments have focused on a very limited number of skeletal muscles. Comparing high-altitude versus low-altitude populations of deer mice, we show that a large number of muscles involved in shivering, locomotion, body posture, ventilation, and mastication exhibit greater mitochondrial enzyme activities in the high-altitude population. Therefore, evolved increases in mitochondrial oxidative capacity across skeletal muscles contribute to high-altitude adaptation.

High-altitude adaptation is accompanied by strong signatures of purifying selection in the mitochondrial genomes of three Andean waterfowl.

Evidence from a variety of organisms points to convergent evolution on the mitochondria associated with a physiological response to oxygen deprivation or temperature stress, including mechanisms for high-altitude adaptation. Here, we examine whether demography and/or selection explains standing mitogenome nucleotide diversity in high-altitude adapted populations of three Andean waterfowl species: yellow-billed pintail (Anas georgica), speckled teal (Anas flavirostris), and cinnamon teal (Spatula cyanoptera). We compared a total of 60 mitogenomes from each of these three duck species (n = 20 per species) across low and high altitudes and tested whether part(s) or all of the mitogenome exhibited expected signatures of purifying selection within the high-altitude populations of these species. Historical effective population sizes (Ne) were inferred to be similar between high- and low-altitude populations of each species, suggesting that selection rather than genetic drift best explains the reduced genetic variation found in mitochondrial genes of high-altitude populations compared to low-altitude populations of the same species. Specifically, we provide evidence that establishment of these three Andean waterfowl species in the high-altitude environment, coincided at least in part with a persistent pattern of negative purifying selection acting on oxidative phosphorylation (OXPHOS) function of the mitochondria. Our results further reveal that the extent of gene-specific purifying selection has been greatest in the speckled teal, the species with the longest history of high-altitude occupancy.

Hypobaric hypoxia drives selection of altitude-associated adaptative alleles in the Himalayan population

Genetic variants play a crucial role in shaping the adaptive phenotypes associated with high-altitude populations. Nevertheless, a comprehensive understanding of the specific impacts of different environments associated with increasing altitudes on the natural selection of these genetic variants remains undetermined. Hence, this study aimed to identify genetic markers responsible for high-altitude adaptation with specific reference to different altitudes, majorly focussing on an altitude elevation range of ∼1500 m and a corresponding decrease of ≥5 % in ambient oxygen availability. We conducted a comprehensive genome-wide investigation (n = 192) followed by a validation study (n = 514) in low-altitude and three high-altitude populations (>2400 m) of Nubra village (NU) (3048 m), Sakti village (SKT) (3812 m), and Tso Moriri village (TK) (4522 m). Extensive genetic analysis identified 86 SNPs that showed significant associations with high-altitude adaptation. Frequency mapping of these SNPs revealed 38 adaptive alleles and specific haplotypes that exhibited a strong linear correlation with increasing altitude. Notably, these SNPs spanned crucial genes, such as ADH6 and NAPG along with the vastly studied genes like EGLN1 and EPAS1, involved in oxygen sensing, metabolism, and vascular homeostasis. Correlation analyses between these adaptive alleles and relevant clinical and biochemical markers provided evidence of their functional relevance in physiological adaptation to hypobaric hypoxia. High-altitude population showed a significant increase in plasma 8-isoPGF2α levels as compared to low-altitude population. Similar observation showcased increased blood pressure in NU as compared to TK (P < 0.0001). In silico analyses further confirmed that these alleles regulate gene expression of EGLN1, EPAS1, COQ7, NAPG, ADH6, DUOXA1 etc. This study provides genetic insights into the effects of hypobaric-hypoxia on the clinico-physiological characteristics of natives living in increasing high-altitude regions. Overall, our findings highlight the synergistic relationship between environment and evolutionary processes, showcasing physiological implications of genetic variants in oxygen sensing and metabolic pathway genes in increasing high-altitude environments.

Dispersal from the Qinghai-Tibet plateau by a high-altitude butterfly is associated with rapid expansion and reorganization of its genome

Parnassius glacialis is a typical “Out of the QTP” alpine butterfly that originated on the Qinghai-Tibet Plateau (QTP) and dispersed into relatively low-altitude mountainous. Here we assemble a chromosome-level genome of P. glacialis and resequence 9 populations in order to explore the genome evolution and local adaptation of this species. These results indicated that the rapid accumulation and slow unequal recombination of transposable elements (TEs) contributed to the formation of its large genome. Several ribosomal gene families showed extensive expansion and selective evolution through transposon-mediated processed pseudogenes. Additionally, massive structural variations (SVs) of TEs affected the genetic differentiation of low-altitude populations. These low-altitude populations might have experienced a genetic bottleneck in the past and harbor genes with selective signatures which may be responsible for the potential adaptation to low-altitude environments. These results provide a foundation for understanding genome evolution and local adaptation for “Out of the QTP” of P. glacialis.

Comparative metabolomics analysis reveals high-altitude adaptations in a toad-headed viviparous lizard, Phrynocephalus vlangalii

Extreme environmental conditions at high altitude, such as hypobaric hypoxia, low temperature, and strong UV radiation, pose a great challenge to the survival of animals. Although the mechanisms of adaptation to high-altitude environments have attracted much attention for native plateau species, the underlying metabolic regulation remains unclear. Here, we used a multi-platform metabolomic analysis to compare metabolic profiles of liver between high- and low-altitude populations of toad-headed lizards, Phrynocephalus vlangalii, from the Qinghai–Tibet Plateau. A total of 191 differential metabolites were identified, consisting of 108 up-regulated and 83 down-regulated metabolites in high-altitude lizards as compared with values for low-altitude lizards. Pathway analysis revealed that the significantly different metabolites were associated with carbohydrate metabolism, amino acid metabolism, purine metabolism, and glycerolipid metabolism. Most intermediary metabolites of glycolysis and the tricarboxylic acid cycle were not significantly altered between the two altitudes, but most free fatty acids as well as β-hydroxybutyric acid were significantly lower in the high-altitude population. This may suggest that high-altitude lizards rely more on carbohydrates as their main energy fuel rather than lipids. Higher levels of phospholipids occurred in the liver of high-altitude populations, suggesting that membrane lipids may undergo adaptive remodeling in response to low-temperature stress at high altitude. In summary, this study demonstrates that metabolic profiles differ substantially between high- and low-altitude lizard populations, and that these differential metabolites and metabolic pathways can provide new insights to reveal mechanisms of adaptation to extreme environments at high altitude.

The putatively high-altitude adaptation of macaque monkeys: Evidence from the fecal metabolome and gut microbiome.

Animals living in high-altitude environments, such as the Tibetan Plateau, must face harsh environmental conditions (e.g., hypoxia, cold, and strong UV radiation). These animals' physiological adaptations (e.g., increased red cell production and turnover rate) might also be associated with the gut microbial response. Bilirubin is a component of red blood cell turnover or destruction and is excreted into the intestine and reduced to urobilinoids and/or urobilinogen by gut bacteria. Here, we found that the feces of macaques living in high-altitude regions look significantly browner (with a high concentration of stercobilin, a component from urobilinoids) than those living in low-altitude regions. We also found that gut microbes involved in urobilinogen reduction (e.g., beta-glucuronidase) were enriched in the high-altitude mammal population compared to the low-altitude population. Moreover, the spatial-temporal change in gut microbial function was more profound in the low-altitude macaques than in the high-altitude population, which might be attributed to profound changes in food resources in the low-altitude regions. Therefore, we conclude that a high-altitude environment's stress influences living animals and their symbiotic microbiota.

Analysis of the Vigor of Pinus hartwegii Lindl. along an Altitudinal Gradient Using UAV Multispectral Images: Evidence of Forest Decline Possibly Associated with Climatic Change

Future climate forecasts predict major changes that will have negative impacts on the distribution, abundance, and dynamics of forest ecosystems. In Mexico, there is evidence of symptoms of massive forest decline; however, there is no consensus in terms of attributing these symptoms to climate change. This study aimed to provide evidence of forest decline possibly associated with climatic change in the highland pine (Pinus hartwegii Lindl.) populations of the Nevado de Toluca Flora and Fauna Protection Area. Using unmanned aerial vehicles (UAV) equipped with multispectral sensors, the study applied digital photogrammetry techniques, automated tree crown detection algorithms, and calculation of the normalized difference vegetation index (NDVI) and leaf chlorophyll index (LCI) to assess forest health across an altitudinal transect (from 3300 m to the timberline at 4040 m elevation). Climate analysis was conducted with TerraClimate data using mean annual temperature (MAT), April temperature, and Palmer Drought Severity Index (PDSI) from the studied altitudinal transect and its xeric limit. We found that lower altitude populations had significantly higher stress levels, indicating forest decline phenomena, while intermediate altitude populations showed greater vigor of the detected trees. Statistically significant differences in the NDVI and LCI values along the altitudinal gradient provided evidence of forest decline in terms of forest vigor and productivity, with the greatest disturbance found at the lower altitude of the examined forest species. The analysis of the climatic data revealed an increase in April temperature +1.4 °C of the xeric limit of the transect (low altitude) when comparing the reference period, 1961–1990 (mean: 12.17 °C), with the decade prior to our study (2011–2020; mean: 13.57 °C). This would be equivalent to an upward shift in elevation of 280 m of the xeric limit. In addition, the PDSI analysis revealed that droughts are becoming increasingly intense at a rate of 0.06 PDSI units per decade, with greater intensity in the last five years. These findings highlight the negative impacts of climate change on forest ecosystems and the urgent need for alternative forest management and conservation practices to increase resilience and adaptation in the temperate forests of Mexico. This study sets a precedent for further research to improve our understanding of the impacts of climate change on forest ecosystems and the development of sustainable management practices.

Metagenome and metabolome insights into the energy compensation and exogenous toxin degradation of gut microbiota in high-altitude rhesus macaques (Macaca mulatta)

There have been many reports on the genetic mechanism in rhesus macaques (RMs) for environmental adaptation to high altitudes, but the synergistic involvement of gut microbiota in this adaptation remains unclear. Here we performed fecal metagenomic and metabolomic studies on samples from high- and low-altitude populations to assess the synergistic role of gut microbiota in the adaptation of RMs to high-altitude environments. Microbiota taxonomic annotation yielded 7471 microbiota species. There were 37 bacterial species whose abundance was significantly enriched in the high-altitude populations, 16 of which were previously reported to be related to the host’s dietary digestion and energy metabolism. Further functional gene enrichment found a stronger potential for gut microbiota to synthesize energy substrate acetyl-CoA using CO2 and energy substrate pyruvate using oxaloacetate, as well as a stronger potential to transform acetyl-CoA to energy substrate acetate in high-altitude populations. Interestingly, there were no apparent differences between low-altitude and high-altitude populations in terms of genes enriched in the main pathways by which the microbiota consumed the three energy substrates, and none of the three energy substrates were detected in the fecal metabolites. These results strongly suggest that gut microbiota plays an important energy compensatory role that helps RMs to adapt to high-altitude environments. Further functional enrichment after metabolite source analysis indicated the abundance of metabolites related to the degradation of exogenous toxins was also significantly higher in high-altitude populations, which suggested a contributory role of gut microbiota to the degradation of exogenous toxins in wild RMs adapted to high-altitude environments.

Extensive prevalence and significant genetic differentiation of Blastocystis in high- and low-altitude populations of wild rhesus macaques in China

BackgroundBlastocystis is a common intestinal protist with a wide range of hosts. Thus far, 38 subtypes have been identified. In recent years, wild animals have been confronted with habitat fragmentation as well as an increasing risk of zoonotic disease transmission due to human disturbance. Only limited data are available on Blastocystis infection and subtype distribution in wild rhesus macaques in China. The aim of the present study was to investigate the prevalence and genetic diversity of Blastocystis in nine wild rhesus macaque populations in China.MethodsA total of 276 faecal samples were collected from five high-altitude populations (high-altitude group [HAG]; 2800–4100 m a.s.l.) and four low-altitude populations (low-altitude group [LAG]; 5–1000 m a.s.l) of rhesus macaques. PCR-based analysis, using a new primer pair for the amplification of a 1690-bp sequence of the small subunit ribosomal RNA (SSU rRNA) gene, was used for prevalence and genetic diversity analysis.ResultAnalysis of faecal samples revealed that Blastocystis infection was common in rhesus macaques, with an infection positivity rate of 80.1% (n = 221/276 samples). There was no significant difference (P = 0.121) in positivity rate between the LAG (84.3%) and HAG (76.8%). Overall, 33 haplotypes were obtained and classified into four subtypes (STs), of which three were potentially zoonotic subtypes (ST1, 29.7%; ST2, 16.7%; ST3, 31.9%) and one that was first identified in this study and named ST39 (12.0%). The STs were distributed differently among the rhesus macaque populations, except for ST3, which was found in all populations. Phylogenetic analyses revealed two major divergent clades of ST3 for the HAG and LAG. Genetic diversity analysis showed a high genetic diversity of ST3 (haplotype diversity: 0.846; nucleotide diversity: 0.014) in the rhesus macaques, but a high genetic differentiation (FST > 0.25) and a low gene flow (Nm = 0.09) between the HAG and LAG.ConclusionOur study, which is the first investigation on Blastocystis infection in multiple wild rhesus macaque populations in China, indicates a potential risk of zoonotic transmission of Blastocystis in the study areas. Blastocystis ST3 showed high genetic diversity in wild rhesus macaques and significant genetic differentiation between the HAG and LAG. Our results provide fundamental information on the genetic diversity and prevalence of Blastocystis in wild rhesus macaque populations.Graphical

A novel mechanism for high-altitude adaptation in hemoglobin of black-spotted frog (Pelophylax nigromaculatus)

Understanding how animals living in highland adapt to extreme conditions is critical to evolutionary biology. In contrast to birds and mammals, little information was available on the adaptation mechanisms for O2 transport in high-altitude ectothermic vertebrates. Here we report for the first time on hematological parameters, amino acid sequences of α and β chains of hemoglobin (Hb), O2 affinity of purified hemoglobins (Hbs) and their sensitivities to anion allosteric effector (H+, Cl−, ATP) and temperature in the high-altitude (2,292 m) black-spotted frogs (Pelophylax nigromaculatus) from the Qinghai-Tibet plateau (QTP) compared with the low-altitude (135 m) population. Our results showed that high-altitude black-spotted frogs exhibit significantly increased relative lung mass, hematocrit, and hemoglobin concentration, but significantly decreased body mass and erythrocyte volume, which could improve the blood O2 carrying capability. Compared with the low-altitude population, the purified Hbs of high-altitude black-spotted frogs possessed significantly higher intrinsic Hb-O2 affinity, similar low anion allosteric effector sensitivities, Bohr effects and temperature sensitivities. The elevated Hb-O2 affinity of highland frogs could maximize the O2 extraction from the lungs. Molecular dynamics simulations showed that the Gln123Glu substitution on α2 chain in highland frogs could form a hydrogen bond with 127Lys on α2 chain, resulting in the elimination of a hydrogen bond between 127Lys on α2 chain and 141Arg on α1 chain. This could weaken the interaction between two semirigid dimers (α1β1 and α2β2) and then lead to the high intrinsic Hb-O2 affinity in high-altitude black-spotted frogs.

Diet and high altitude strongly drive convergent adaptation of gut microbiota in wild macaques, humans, and dogs to high altitude environments.

Animal gut microbiota plays an indispensable role in host adaptation to different altitude environments. At present, little is known about the mechanism of animal gut microbiota in host adaptation to high altitude environments. Here, we selected wild macaques, humans, and dogs with different levels of kinship and intimate relationships in high altitude and low altitude environments, and analyzed the response of their gut microbiota to the host diet and altitude environments. Alpha diversity analysis found that at high altitude, the gut microbiota diversity of wild macaques with more complex diet in the wild environments is much higher than that of humans and dogs with simpler diet (p < 0.05), and beta diversity analysis found that the UniFrac distance between humans and dogs was significantly lower than between humans and macaques (p < 0.05), indicating that diet strongly drive the convergence of gut microbiota among species. Meanwhile, alpha diversity analysis found that among three subjects, the gut microbiota diversity of high altitude population is higher than that of low altitude population (ACE index in three species, Shannon index in dog and macaque and Simpson index in dog, p < 0.05), and beta diversity analysis found that the UniFrac distances among the three subjects in the high altitude environments were significantly lower than in the low altitude environments (p < 0.05). Additionally, core shared ASVs analysis found that among three subjects, the number of core microbiota in high altitude environments is higher than in low altitude environments, up to 5.34 times (1,105/207), and the proportion and relative abundance of the core bacteria types in each species were significantly higher in high altitude environments than in low altitude environments (p < 0.05). The results showed that high altitude environments played an important role in driving the convergence of gut microbiota among species. Furthermore, the neutral community model trial found that the gut microbiota of the three subjects was dispersed much more at high altitude than at low altitude, implying that the gut microbiota convergence of animals at high altitudes may be partly due to the microbial transmission between hosts mediated by human activities.

Impacts of oxygen deficiency on embryo life-history traits of migratory locust Locusta migratoria from low and high altitudes.

Hypoxia challenges aerobic organisms in numerous environments, and hypoxic conditions may become more severe under future climate-change scenarios. The impact of hypoxia on the development of terrestrial insect embryos is not well understood. Here, to address this gap, embryonic life-history traits of migratory locust Locusta migratoria from low-altitude and high-altitude regions were compared under 2 oxygen levels: normoxia (i.e., 21 kPa oxygen partial pressure and mild hypoxia (i.e., 10 kPa oxygen partial pressure). Our results demonstrated that, whether reared under normoxia or mild hypoxia, L. migratoria from high-altitude populations had longer developmental times, reduced weight, and lower mean relative growth rate as compared with those from low-altitude populations. When transferred from normoxia to mild hypoxia, nearly all the tested life-history traits presented significant negative changes in the low-altitude populations, but not in the high-altitude populations. The factor 'strain' alone explained 18.26%-54.59% of the total variation for traits, suggesting that the phenotypic differences between L. migratoria populations from the 2 altitudes could be driven by genetic variation. Significant genetic correlations were found between life-history traits, and most of these showed differentiation between the 2 altitudinal gradients. G-matrix comparisons showed significant structural differences between L. migratoria from the 2 regions, as well as several negative covariances (i.e., trade-offs) between traits in the low-altitude populations. Overall, our study provides clear evidence that evolutionary divergence of embryonic traits between L. migratoria populations from different altitudes has occurred.

A Comparative Study on the Drivers of Forest Fires in Different Countries in the Cross-Border Area between China, North Korea and Russia

The occurrence and spread of forest fires are the result of the interaction of many factors. In cross-border areas, different fire management systems may lead to different forest fire driving factors. A comparative analysis of the forest fire driving factors in different countries can help to provide ideas for fire prevention and control. In this study, based on the logistic regression (LR) model and standardized coefficients, we determined the relative impact of forest fire driving factors in different countries, in the cross-border area between China, North Korea and Russia from 2001 to 2020, and established a forest fire probability and fire risk level division using a Kriging interpolation. The results show that the climate is the most important factor affecting the probability of forest fires in the cross-border area, followed by the topography and vegetation factors; human activities have the least influence. From a country-by-country perspective, the forest fires on the Chinese side were more affected by humans than on the North Korean and Russian sides and they were mainly concentrated in areas with a low altitude and high population density. The forest fires on the North Korean side and the Russian side were more affected by nature than on the Chinese side and were mainly concentrated in areas with a low altitude, high temperature and little rainfall. The high-risk areas for forest fires were mostly concentrated near the border between China, North Korea and Russia, where transboundary fires pose a great threat to forest resources and rare animals. This study shows that there is a significant difference between the impact of different forest fire management systems on fire conditions, and that active forest fire control policies can effectively reduce the damage caused by forest fires. Due to the complexity of the geopolitics in cross-border areas, transboundary firefighting faces certain difficulties. In the future, it will be necessary to strengthen the cooperation between countries and establish transboundary joint defenses against forest fires in order to protect the declining forest resources and the habitats of rare animals.

Accumulation of population polymorphisms in the mitonuclear genome with probable adaptive effect to extreme environments as altitude for forensic purposes

We analyzed the accumulation of population polymorphism in 2504 individuals - nuclear genomes (nDNA) of 26 populations (81 genes associated to extreme environments) and 3295 mitochondrial genomes (mtDNA) of 47 populations with the aim to found mitonuclear relationship associated an extremes environment as altitude. For that, we use an algorithm developed by us to determine the accumulation of polymorphisms by segments in the genome and thus be able to perform the multivariate analysis to found SNPs differences and similarities among populations. The results showed in Peruvian population a statistically significant mitonuclear relationship for 113/293970 nDNA SNPs in 16/81 genes. In the case of the mtDNA, we found a statistically significant mitonuclear relationship for 6/22 mtDNA positions – Gene. Additionally for the Peruvian population, the MRPP3 had the greatest polymorphism contribution with respect to other populations. Then, these nDNA and mtDNA SNPs in genetically close populations to Peru can be applied to forensic genomic phenotyping to identify groups likely adapted to extreme conditions (such as altitude) or make individualization between low and high altitude populations.