Low Oxygen Environment Research Articles

Characteristics of transcriptome and chromatin accessibility in the peripheral blood after acute hypoxia exposure

BackgroundHuman responses and acclimation to the environmental stresses of high altitude and low oxygen are multifaceted and regulated by multiple genes. However, the mechanism of how the body adjusts in a low-oxygen environment is not yet clear.ResultsHence, we performed RNA sequencing (RNA-seq) and ATAC sequencing (ATAC-seq) to observe the changes of transcriptome and chromatin accessibility in the peripheral blood of eight individuals at 1 h post adaptation in a simulated plateau environment with 3500 m and 4500 m altitude, respectively. Differential expression analysis and the Boruta algorithm identified differentially expressed genes (DEGs) and differentially accessible regions (DARs) associated with hypoxia adaptation. Specifically, RNA-seq identified 93 and 7 DEGs after 1 h post adaptation with 3500 m altitude and 45 and 8 DEGs after 1 h adaptation with 4500 m. Additionally, ATAC-seq screened 12 and 4 DARs in 3500 m altitude adaption and 15 and 5 DARs in 4500 m altitude adaption. Moreover, the combined analysis of RNA-seq and ATAC-seq revealed that 10 hub genes were independently identified from the protein–protein interaction (PPI) network for each altitude. Gene enrichment analysis displayed that most hub genes were related with hypoxia pathways.ConclusionsOur results can provide the reference for the early response of the organism to hypoxic adaptation.

The impact of a high-carbohydrate diet on the cognitive behavior of mice in a low-pressure, low-oxygen environment.

The effectiveness of high-carbohydrate diets (HCD) on cognitive impairment is still being debated. To clarify the impact of HCD on the cognitive behavior of mice under low-pressure hypoxic conditions, we studied 24 mice in different environments while subjecting them to dietary intervention for 5 weeks, and conducting behavioral tests. Under low-pressure hypoxic conditions, HCD intervention reversed the decline in spatial learning and memory abilities in mice caused by hypoxia, ameliorated pathological brain damage, and restored the integrity of the intestinal mucosa. We also identified differences in the microbial community. Under low-pressure hypoxic conditions, the intestinal abundance of Parasutterella in mice decreased, the abundance of harmful bacteria such as Desulfovibrio increased, and apoptosis was more prevalent, possibly explaining the observed decreases in glutathione peroxidase activity and brain-derived neurotrophic factor (BDNF) expression in the brain. HCD intervention increased the intestinal abundance of Bifidobacterium in hypoxic mice, reduced the abundances of Desulfovibrio and Faecalibaculum, and played antioxidant roles by lowering malondialdehyde levels and increasing superoxide dismutase activity in the brain by metabolizing amino acids and lipids. HCD also upregulated hippocampal BDNF levels and downregulated caspase 3. Collectively, these results are important because they help explain how HCD intervention can reduce hypoxia-induced damage to brain function.

Creating a Halotolerant Degrader for Efficient Mineralization of p-Nitrophenol-Substituted Organophosphorus Pesticides in High-Saline Wastewater.

The bioaugmentation performance is severely reduced in the treatment of high-saline pesticide wastewater because the growth and degradation activity of pesticide degraders are significantly inhibited by high salt concentrations. In this study, a heterologous biodegradation pathway comprising the seven genes mpd/pnpABCDEF responsible for the bioconversion of p-nitrophenol (PNP)-substituted organophosphorus pesticides (OPs) into β-oxoadipate and the genes encoding Vitreoscilla hemoglobin (VHb) and green fluorescent protein (GFP) were integrated into the genome of a salt-tolerant chassis Halomonas cupida J9, to generate a genetically engineered halotolerant degrader J9U-MP. RT-PCR assays demonstrated that the nine exogenous genes are successfully transcribed to mRNA in J9U-MP. Gas chromatography analysis of methyl parathion (MP) and its intermediates demonstrated that the expressed MP hydrolase and PNP-degrading enzymes PnpABCD show obvious degradation activity toward the specific substrates in J9U-MP. Stable isotope analysis showed that J9U-MP is able to efficiently convert 13C6-PNP into 13CO2, demonstrating the complete mineralization of MP in high-salt media. J9U-MP is genetically stable during passage culture, and genomic integration of exogenous genes does not negatively influence the growth of J9U-MP. Under oxygen-limited conditions, VHb-expressing J9U-MP does not show obvious growth inhibition and a significant reduction in the MP degradation rate. A real-time monitoring system with enhanced GFP is used to track the motion and activity of J9U-MP during bioremediation. Moreover, 50 mg/L MP and its intermediates (i.e., PNP and HQ) were completely degraded by J9U-MP within 12 h in wastewater supplemented with 60 g/L NaCl. After 3 days of incubation, 25 mg/L 13C6-PNP was converted into 13CO2 by J9U-MP in wastewater supplemented with 60 g/L NaCl. Our results highlight the power of synthetic biology for creating new halotolerant pollutant-mineralizing strains. The strong competitive advantages of J9U-MP in high-salinity and low-oxygen environments make this degrader suitable for in situ bioaugmentation of OP wastewater.

Engineered hypoxia-responsive albumin nanoparticles mediating mitophagy regulation for cancer therapy

Hypoxic tumors present a significant challenge in cancer therapy due to their ability to adaptation in low-oxygen environments, which supports tumor survival and resistance to treatment. Enhanced mitophagy, the selective degradation of mitochondria by autophagy, is a crucial mechanism that helps sustain cellular homeostasis in hypoxic tumors. In this study, we develop an azocalix[4]arene-modified supramolecular albumin nanoparticle, that co-delivers hydroxychloroquine and a mitochondria-targeting photosensitizer, designed to induce cascaded oxidative stress by regulating mitophagy for the treatment of hypoxic tumors. These nanoparticles are hypoxia-responsive and release loaded guest molecules in hypoxic tumor cells. The released hydroxychloroquine disrupts the mitophagy process, thereby increasing oxidative stress and further weakening the tumor cells. Additionally, upon laser irradiation, the photosensitizer generates reactive oxygen species independent of oxygen, inducing mitochondria damage and mitophagy activation. The dual action of simultaneous spatiotemporal mitophagy activation and mitophagy flux blockade results in enhanced autophagic and oxidative stress, ultimately driving tumor cell death. Our work highlights the effectiveness of hydroxychloroquine-mediated mitophagy blockade combined with mitochondria-targeted photosensitizer for cascade-amplified oxidative stress against hypoxic tumors.

Carbonic anhydrase IX inhibition as a path to treat neuroblastoma.

Tumour hypoxia frequently presents a major challenge in the treatment of neuroblastoma (NBL). The neuroblastoma cells produce carbonic anhydrase IX (CA IX), an enzyme crucial for the survival of cancer cells in low-oxygen environments. We designed and synthesised a novel high-affinity inhibitor of CA IX. The highest to-date. The affinities were determined for all human catalytically active CA isozymes showing significant selectivity for CA IX over other isozymes. The inhibitor effect on neuroblastoma cancer cell growth was determined in vitro and in vivo via a mice xenograft model. The novel designed inhibitor effectively mitigated the acidification induced by CA IX and reduced spheroid growth under hypoxic conditions in the SK-N-AS cell line. It also diminished the secretion of pro-tumour chemokines IL-8 (CXCL2) and CCL2. When we combined this novel CA IX inhibitor with a compound that inhibits the chemokine receptor CCR2 protein activity, we observed a reduction in mouse tumour growth. The combined treatment also prompted tumours to exhibit adaptive resistance by producing higher levels of vascular endothelial growth factor receptors (VEGFR) and other compensatory signals. This research underscores the pivotal role of CA IX in cancer and the potential of a novel CA IX inhibitor-based combination intervention therapy for neuroblastoma treatment.

Co-delivery of antioxidants and siRNA-VEGF: promising treatment for age-related macular degeneration.

Current treatments for retinal disorders are anti-angiogenic agents, laser photocoagulation, and photodynamic therapies. These conventional treatments focus on reducing abnormal blood vessel formation in the retina, which, in a low-oxygen environment, can lead to harmful proliferation of endothelial cells. This results in dysfunctional, leaky blood vessels that cause retinal edema, hemorrhage, and vision loss. Age-related Macular Degeneration is a primary cause of vision loss and blindness in the elderly, impacting around 20% of those over 50 years old. This complex disease is also closely related to oxidative stress in retina. In this review, we explore the challenge of treating retinal diseases, alternatives and possibilities of enhancing the effectiveness of therapies using co-delivery systems containing both antiangiogenic and antioxidant therapeutic agents. Despite recent proposals potential, the lack of extensive clinical studies on the long-term outcomes and optimal combinations of therapies means that the full risk profile and effectiveness of combined therapy are not yet completely understood. These factors must be carefully considered and managed by healthcare providers to optimize treatment outcomes and ensure patient safety.

Heterotis niloticus (African Bonytongue) Domestication: Potentials, Efforts, and Challenges

Heterotis niloticus is a fascinating freshwater fish species popularly referred to as the African bonytongue. It offers great potential for aquaculture due to its rapid growth, flesh quality, adaptability to low oxygen environments, and high market value. Domestication efforts for this species have been initiated to optimize its production and meet the increasing global demand for sustainable protein sources. This review explores the current state of H. niloticus domestication and highlights the key challenges and opportunities. Despite their promising potential, several obstacles remain, including the development of efficient hatchery techniques, optimization of feed formulations, and disease control. Overcoming these challenges is essential to promote the full potential of H. niloticus aquaculture and contribute to improved food security. Future research should focus on refining breeding programs, improving water quality management, and exploring innovative aquaculture systems. Policy support is key to driving investments, innovation, conservation efforts, and the sustainable development of H. niloticus aquaculture.

Transcriptome and Evolutionary Analysis of Pseudotrichomonas keilini, a Free-Living Anaerobic Eukaryote.

The early evolution of eukaryotes and their adaptations to low-oxygen environments are fascinating open questions in biology. Genome-scale data from novel eukaryotes, and particularly from free-living lineages, are the key to answering these questions. The Parabasalia are a major group of anaerobic eukaryotes that form the most speciose lineage of Metamonada. The most well-studied are parasitic parabasalids, including Trichomonas vaginalis and Tritrichomonas foetus, but very little genome-scale data are available for free-living members of the group. Here, we sequenced the transcriptome of Pseudotrichomonas keilini, a free-living parabasalian. Comparative genomic analysis indicated that P. keilini possesses a metabolism and gene complement that are in many respects similar to its parasitic relative T. vaginalis and that in the time since their most recent common ancestor, it is the T. vaginalis lineage that has experienced more genomic change, likely due to the transition to a parasitic lifestyle. Features shared between P. keilini and T. vaginalis include a hydrogenosome (anaerobic mitochondrial homolog) that we predict to function much as in T. vaginalis and a complete glycolytic pathway that is likely to represent one of the primary means by which P. keilini obtains ATP. Phylogenomic analysis indicates that P. keilini branches within a clade of endobiotic parabasalids, consistent with the hypothesis that different parabasalid lineages evolved toward parasitic or free-living lifestyles from an endobiotic, anaerobic, or microaerophilic common ancestor.

Insights into the spatial ecology of the world’s most ancient dog: high-altitude movements of New Guinea dingoes

Knowledge of an animal’s activity patterns, home range size and space use is fundamental to understanding their basic ecology, and obtaining spatial data is an important research priority for newly discovered species, data-deficient species of conservation concern, or species of great scientific or public interest. Here we report the first spatial data obtained from wild-living dingoes near Puncak Jaya, New Guinea. Based on information from four dingoes monitored with GPS tracking collars between 2018 and 2022, we report that dingo home range sizes can be up to 128km2, dingoes travel up to 56.8km per day, and they utilise rainforest and alpine habitats up to 4,630m above sea level. Dingoes at the site regularly traversed steep, rocky and barren alpine mountain crevasses to access more fertile areas at lower altitudes on the other side. These results imply that New Guinea dingoes may have physiological and genetic adaptations that enable them to live in high-altitude low-oxygen environments similar to Himalayan wolves, Ethiopian wolves, and other canids found in high-altitude areas. As the first domesticated animal and the world’s most ancient dog, and given their historic and current cultural significance, their illusiveness in the wild, and their trophic position as the largest terrestrial predators on the second-largest island in the world, we believe that further research on the ecology of New Guinea dingoes will continue to reveal important insights valuable for our understanding of human and animal ecology in this global biodiversity hotspot.

Decoding the molecular pathways governing trophoblast migration and placental development; a literature review.

Placental development is a multifaceted process critical for a fruitful pregnancy, reinforced by a complex network of molecular pathways that synchronize trophoblast migration, differentiation, and overall placental function. This review provides an in-depth analysis of the key signaling pathways, such as Wnt, Notch, TGF-β, and VEGF, which play fundamental roles in trophoblast proliferation, invasion, and the complicated process of placental vascular development. For instance, the Wnt signaling pathway is essential to balance trophoblast stem cell proliferation and differentiation, while Notch signaling stimulates cell fate decisions and invasive behavior. TGF-β signaling plays a critical role in trophoblast invasion and differentiation, predominantly in response to the low oxygen environment of early pregnancy, regulated by hypoxia-inducible factors (HIFs). These factors promote trophoblast adaptation, ensure proper placental attachment and vascularization, and facilitate adequate fetal-maternal exchange. Further, we explore the epigenetic and post-transcriptional regulatory mechanisms that regulate trophoblast function, including DNA methylation and the contribution of non-coding RNAs, which contribute to the fine-tuning of gene expression during placental development. Dysregulation of these pathways is associated with severe pregnancy complications, such as preeclampsia, intrauterine growth restriction, and recurrent miscarriage, emphasizing the critical need for targeted therapeutic strategies. Finally, emerging technologies like trophoblast organoids, single-cell RNA sequencing, and placenta-on-chip models are discussed as innovative tools that hold promise for advancing our understanding of placental biology and developing novel interventions to improve pregnancy outcomes. This review emphasizes the importance of understanding these molecular mechanisms to better address placental dysfunctions and associated pregnancy disorders.

Molecular compositional variation of organic matter deposited on the East Tasman Plateau during the Paleocene–Eocene Thermal Maximum

Molecular compositions in sediments collected by Ocean Drilling Program Leg 189 at Site 1172 in the Tasmanian Gateway, Australia have been characterised by gas chromatography–mass spectrometry to assess the impact of the Paleocene–Eocene Thermal Maximum (PETM) on organic matter origins and evolution. Total organic carbon (TOC) and sulfur contents reach the lowest values immediately before the initiation of the negative carbon isotope excursion (CIE) in the shallow marine environment on the East Tasman Plateau. The TOC content increases slightly while the sulfur content increases more substantially during deposition of the CIE, suggesting the occurrence of low-oxygen environments during the PETM event. The studied section is thermally immature, as shown by the dominance of biological configuration biomarkers such as 17β(H),21β(H)-hopanes (ββ) and hopenes. Changes in relative abundance of compound classes and isomer ratios are largely caused by the variation of source inputs and depositional conditions. Very low abundance of marine steroids during the CIE, but very enriched hopanoids, indicate low marine productivity, in accord with substantial remineralisation of organic matter in the bottom waters. The ββ-hopanes are the most abundant hopanoid series, followed by the neohop-13(18)-ene and hop-17(21)-ene series, further verifying the immaturity of the organic constituents in the samples. Hopane ratios (ββ/(βα + αβ) and βα/(βα + αβ) with different carbon numbers are systematically higher in sediments deposited during the CIE than those formed pre- and post-CIE, suggest increased bacterial inputs. Higher C30/C29 and C30/C31 hopanoid ratios in the CIE sediments are consistent with a greater contribution from in situ bacterial organic matter, rather than continental soil erosion by flooding. This is supported by the higher C27–32 hopanoids/(C27 + C29 + C31n-alkanes) ratio and sulfur content during the CIE. A relatively lower TOC content in the sediments formed during the PETM is inferred to have been caused by dilution by both enhanced detrital input and intensified bacterial consumption. This study demonstrates that the biomarker approach can play an important role in the identification of organic matter origin and characterisation of depositional environment for PETM sequences.

Enhanced sulfide burial in low-oxygen aquatic environments could offset the carbon footprint of aquaculture production.

Carbon removal from the atmosphere is needed to keep global mean temperature increases below 2 °C. Here, we develop a model to explore how alkalinity production through enhanced iron sulfide formation in low-oxygen aquatic environments, such as aquaculture systems, could offer a cost-effective means of CO2 removal. We show that enhanced sulfide burial through the supply of reactive iron to surface sediments may be able to capture up to a hundred million tonnes of CO2 per year, particularly in countries with the highest number of fish farms, such as China and Indonesia. These efforts could largely offset the carbon footprint associated with their aquaculture industry. Enhanced sulfide burial could directly benefit both fish farms and surrounding ecosystems by removing toxic sulfide from aquatic systems, providing an addition to durable global CO2 removal markets and a path towards large-scale, carbon-neutral aquatic food production.

CSIG-14. ACROLEIN INDUCES THE MIR-30A-5P/NCAM AXIS THROUGH THE AKT/GSK3Β/Β-CATENIN PATHWAY, PROMOTING GLIOMA PROGRESSION

Abstract Glioblastoma (GBM), the most aggressive brain tumor, exhibits resistance to treatment and thrives in low-oxygen (hypoxic) environments, leading to the accumulation of reactive oxygen species (ROS). Hypoxia activates the hypoxia-inducible factor (HIF)-1α pathway, enhancing tumor malignancy. Acrolein, a reactive aldehyde produced during lipid peroxidation in hypoxia, induces toxicity through DNA damage, inflammation, mitochondrial dysfunction, and oxidative stress. Our previous study found elevated acrolein levels in hypoxic glioma cells and linked acrolein-induced DNA damage (Acr-dG) with poor GBM prognosis. However, the role of acrolein in GBM progression remains unclear. This study aims to elucidate the impact of acrolein on GBM. In vitro experiments demonstrated acrolein production under hypoxia, which increased glioma cell migration and spheroid formation. RNA sequencing identified five affected pathways: cell adhesion molecules, PI3K-AKT signaling, ECM-receptor interaction, MAPK signaling, and neuroactive ligand-receptor interaction. Acrolein downregulated NCAM (neural cell adhesion molecule) via the miR-30a-5p-AKT-GSK3β/β-catenin axis in GBM cell lines and patient-derived cells. Overexpressing NCAM reduced cell migration and spheroid formation. Lower NCAM levels in GBM tissues correlated with poor patient survival. This study suggests the potential of NCAM as a therapeutic target for GBM and provides insights into early detection and treatment strategies for this malignancy.

CSIG-15. ACROLEIN INDUCES THE MIR-30A-5P/NCAM AXIS VIA THE AKT/GSK3Β/Β-CATENIN PATHWAY, PROMOTING GLIOMA PROGRESSION

Abstract Glioblastoma (GBM), the most aggressive brain tumor, exhibits resistance to treatment and thrives in low-oxygen (hypoxic) environments, leading to the accumulation of reactive oxygen species (ROS). Hypoxia activates the hypoxia-inducible factor (HIF)-1α pathway, enhancing tumor malignancy. Acrolein, a reactive aldehyde produced during lipid peroxidation in hypoxia, induces toxicity through DNA damage, inflammation, mitochondrial dysfunction, and oxidative stress. Our previous study found elevated acrolein levels in hypoxic glioma cells and linked acrolein-induced DNA damage (Acr-dG) with poor GBM prognosis. However, the role of acrolein in GBM progression remains unclear. This study aims to elucidate the impact of acrolein on GBM. In vitro experiments demonstrated acrolein production under hypoxia, which increased glioma cell migration and spheroid formation. RNA sequencing identified five affected pathways: cell adhesion molecules, PI3K-AKT signaling, ECM-receptor interaction, MAPK signaling, and neuroactive ligand-receptor interaction. Acrolein downregulated NCAM (neural cell adhesion molecule) via the miR-30a-5p-AKT-GSK3β/β-catenin axis in GBM cell lines and patient-derived cells. Overexpressing NCAM reduced cell migration and spheroid formation. Lower NCAM levels in GBM tissues correlated with poor patient survival. This study suggests the potential of NCAM as a therapeutic target for GBM and provides insights into early detection and treatment strategies for this malignancy.

Transcriptomic and Metabolomic Insights into Age-Related Changes in Lung Tissue of Yaks Under Highland Stress.

As an indigenous species on the Tibetan Plateau, the yak is well adapted to the plateau hypoxic environment. The high-altitude hypoxia adaptation of the yak requires the adaptive reshaping of multiple tissues and organs, especially the lungs. To reveal the adaptive development of yak lungs under hypoxic stress at the tissue and molecular levels, we conducted histomorphological observations as well as transcriptomic and metabolomic studies of yak lungs at three ages (0.5, 2.5, and 4.5 years). The results showed that the lung tissue developed significantly with age. The mean alveolar area was higher (p < 0.01) in 4.5 and 2.5-year-old yaks than in 0.5-year-old yaks. The percentage of elastic fibers, micro-arterial wall thickness, and micro-arterial area showed an increasing trend (p < 0.01) from 0.5-year-old yaks to 2.5-year-old yaks and then to 4.5-year-old yaks. In addition, some critical differentially expressed genes related to angiogenesis (MYC, EPHA2, TNF), fiber formation (EREG), smooth muscle proliferation (HBEGF), erythropoiesis (SOCS3), and hypoxia response (ZFP36) were identified. Some metabolites associated with these genes were also found simultaneously. These findings provide a deeper understanding of the molecular strategies underlying this species' extraordinary ability to survive normally in low-oxygen environments. In conclusion, the lungs of yaks undergo continuous adaptive development under hypoxic stress, and these findings are crucial for understanding the molecular mechanisms by which native species of the Tibetan Plateau survive in harsh environments.

Study on Microstructure Evolution Characteristics of Coal in Low Temperature Oxidation Stage in Goaf of Longfeng Coal Mine

ABSTRACT Low temperature oxidation of coal is the nature of oxidation of coal with oxygen molecules at temperatures below its oxidation critical point or ignition point, usually from ambient temperature to about 200°C. Air leakage and uneven oxygen distribution significantly impact coal spontaneous combustion in goaf. Understanding the changes in free radicals and functional groups during low-temperature oxidation of coal under different oxygen concentrations is crucial for preventing and controlling residual coal self-ignition. This study employs Fourier transform infrared spectroscopy to analyze the effects of varying oxygen concentrations (3%, 5%, 9%, 15%, 21%) on functional groups and structural parameters during coal’s low-temperature oxidation. Results indicate that increasing oxygen concentration promotes the consumption of oxygen-containing functional groups, reducing their content from 71.9% to 52%. Concurrently, the activity and content of aromatic hydrocarbon functional groups rise rapidly from 4.8% to 52.6%. The aliphatic hydrocarbon structure shows a downward trend, indicating its minimal presence. Aromatic ring condensation increases coal sample aromaticity, suggesting higher maturity and weaker hydrocarbon generation potential, with minimal effect from oxygen concentration. Early-stage reactions show little change in coal’s basic structure, and coal-oxygen reactions remain low in low oxygen environments. This study provides an important basis for understanding the mechanism of coal spontaneous combustion in goaf and formulating effective prevention measures for coal spontaneous combustion.

The dominant mechanisms of nutrient cycling in high-dam reservoirs: retention, transport or transformation?

Abstract High-dam reservoirs can significantly affect nutrient cycling processes across the globe. However, the research community now has two contradictive views (i.e. retention versus transformation) about the impact of high-dam reservoirs on nutrient cycling due to incomplete information obtained from limited field samplings. To resolve this issue, we develop a physically-based, three-dimensional water quality model to examine the spatiotemporal distributions of biogenic elements (nitrogen and phosphorus) in high-dam reservoirs with high spatial and temporal details. We apply the model to the Xiaowan Reservoir, a representative high-dam reservoir in the Lancang River Basin. By scrutinizing the spatiotemporal distributions of biogenic elements across space and over time, we find a unique ‘retention-transformation-transportation’ process of nitrogen and phosphorus in the high-dam reservoir, with dominant transformation occurring in the water zone before the dam during non-flood period while dominant retention occurring in the middle part of a reservoir during flood period. We further find that transformations of biogenic elements are enhanced only in low-temperature and low-oxygen environments. Our findings show solid scientific basis to resolve the contradictive views about nutrient cycling mechanisms in high-dam reservoirs, and provide important policy implications for the operation of high-dam reservoirs to achieve improved water quality while maintaining clean energy supply.

Comparative Analysis of Gene Expression at Sea Level and High Altitude: A Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) Approach.

This research studies the gene expression in response to different oxygen environments and looks at high vs low oxygen environments. Tracking down the activity of some of these genes, namely VHLEL, VEGF and HIF-1α, quantitative real-time polymerase chain reaction (PCR) analysis was done for the study group at sea level in Jeddah and at high altitude in Taif city. It has been found that these genes are much more active in higher altitudes which indicates that there is a biological mechanism that makes those specific sites more oversized for the issue of low oxygen. This knowledge is beneficial as it helps in understanding how people grow to live in high-altitude regions. This is positive, especially in justifying the use of the methods in treatment of altitude sickness and other related diseases. Although these findings bring some hope, it would be equally important to include more participants in future studies in order to consolidate our findings and gain deeper understanding of physiological adaptation in low oxygen. This research work has potential significant contribution to the medical profession under conditions of similar environment.

Haemoglobin Gene Repertoire in Teleost and Cichlid Fishes Shaped by Gene Duplications and Genome Rearrangements.

Haemoglobin is a key molecule for oxygen transport in vertebrates. It exhibits remarkable gene diversity in teleost fishes, reflecting adaptation to various aquatic environments. In this study, we present the dynamic evolution of haemoglobin subunit genes based on a comparison of high-quality genome assemblies of 24 vertebrate species, including 17 teleosts (of which six are cichlids). Our findings indicate that teleost genomes contain a range of haemoglobin genes, from as few as five in fugu to as many as 43 in salmon, with the latter being the largest repertoire found in vertebrates. We find evidence that the teleost ancestor had at least four Hbα and three or four Hbβ subunit genes, and that the current gene diversity emerged during teleost radiation, driven primarily by (tandem) gene duplications, genome compaction, and rearrangement dynamics. We provide insights into the genomic organisation of haemoglobin clusters in different teleost species. We further show that the evolution of paralogous rhbdf1 genes flanking both teleost clusters (LA and MN) supports the hypothesis for the origin of the LA cluster by rearrangement within teleosts, rather than by the teleost specific whole-genome duplication. We specifically focus on cichlid fishes, where adaptation to low oxygen environment plays role in species diversification. Our analysis of six cichlid genomes, including Pungu maclareni from the Barombi Mbo crater lake, for which we sequenced a representative genome, reveals 18-32 copies of the Hb genes, and elevated rates of non-synonymous substitutions compared to other teleosts. Overall, this work facilitates a deeper understanding of how haemoglobin genes contribute to the adaptive potential of teleosts.

Screening of functional genes for hypoxia adaptation in Tibetan pigs by combined genome resequencing and transcriptome analysis.

The high-altitude, low-oxygen environment of the Qinghai-Tibet Plateau poses significant challenges for the introduction of superior livestock breeds. However, local plateau species have adapted to thrive and reproduce under these harsh conditions. Understanding the molecular mechanisms behind plateau animals' adaptation to low-oxygen environments is essential for breeding livestock suited to high-altitude regions. Tibetan pigs, which have undergone long-term natural selection and artificial breeding, have developed the ability to survive and reproduce in hypoxic environments. In this study, we conducted whole-genome resequencing of 30 Tibetan pigs from high-altitude regions and 30 Diannan small-ear pigs from low-altitude areas, to identify candidate genes that support Tibetan pigs' adaptation to hypoxic conditions through selection signal analysis. Additionally, we performed transcriptome sequencing on five tissues (heart, liver, spleen, lung, and bone marrow) from both Tibetan pigs and Diannan small-ear pigs to identify genes with significant differential expression between the two breeds. We then integrated the genomic and transcriptomic data by examining the expression of candidate genes identified in selection signal analysis across different tissues. The selection signal analysis identified 10 genes-HES4, ANGPT1, HIF3A, SPHK2, PCK2, RCN3, HIGD2A, DNM2, IRF9, and SRF-that were under positive selection in the Tibetan pig population and are associated with hypoxia adaptation. When combined with transcriptome data, we found that five of these genes-HIF3A, RCN3, HIGD2A, PCK2, and IRF9-exhibited differential expression. Through an integrated approach of selection signal and transcriptome analysis, we identified five key functional genes that contribute to the adaptation of Tibetan pigs to hypoxic environments. These findings offer new insights into the adaptability of plateau animals.