Poikilothermic animals living in high-altitude environments can be greatly affected by the anaerobic metabolism and lactate recycling, which are catalyzed by an enzyme called lactate dehydrogenase(LDH). However, the f...Poikilothermic animals living in high-altitude environments can be greatly affected by the anaerobic metabolism and lactate recycling, which are catalyzed by an enzyme called lactate dehydrogenase(LDH). However, the function and possible regulatory mechanisms of their anaerobic glycolysis remained elusive. We compared the difference in LDH between a native high-altitude(4 353 m) lizard, Phrynocephalus erythrurus, and a closely related species, Phrynocephalus przewalskii that lives in intermediate altitude environment(1 400 m). The activity of LDH, the concentration of lactate, the distribution of isoenzyme, and the mRNA amounts of Ldh-A and Ldh-B were determined. In cardiac muscle, the lactate-forming activity of P. erythrurus in LDH was higher than of P. przewalskii LDH at all three temperatures tested(10 °C, 25 °C and 35 °C), while lactate-oxidation activity of LDH was significantly different between the two species only at 25 °C and 35 °C. In skeletal muscle, both lactate-forming and lactate-oxidation rates of P. erythrurus were lower than that of P. przewalskii. There was a higher proportion of H subunit and a significantly higher expression of Ldh-B, with a concomitant decrease of lactate concentration in P. erythrurus. These results indicate that P. erythrurus may have a strong potential for anaerobic metabolism, which is likely adapted to the hypoxic environment at high altitudes. Furthermore, P. erythrurus is capable of oxidizing more lactate than P. przewalskii. The Ldh-A cDNA of the two species consists of a 999 bp open reading frame(ORF), which encodes 332 amino acids, while Ldh-B cDNA consists of a 1 002 bp ORF encoding 333 amino acids. LDHA has the same amino acid sequence between the two species, but three amino acid substitutions(V12 I, N21S and N318K) were observed in LDHB. Structure analysis of LDH indicated that the substitutions of residues Val12 and Asp21 in P. erythrurus could be responsible for the highaltitude adaptation. The LDH characteristics of LDH in P. erythrurus suggest unique adaptation strategies of anaerobic metabolism in hypoxia and cold environments at high altitudes for poikilothermic animals.展开更多
To investigate genetic mechanisms of high altitude adaptations of animals living in the Tibetan Plateau, three mitochondrial genomes （mt-genome） of Tibetan horses living in Naqu （4,500 m） of Tibetan, Zhongdian （3...To investigate genetic mechanisms of high altitude adaptations of animals living in the Tibetan Plateau, three mitochondrial genomes （mt-genome） of Tibetan horses living in Naqu （4,500 m） of Tibetan, Zhongdian （3,300 m） and Deqin （3,100 m） of Yunnan province were sequenced. The structures and lengths of these three mt-genomes are similar to the Cheju horse, which is related to Tibetan horses, but little shorter than the Swedish horse. The pair-wise identity of these three horses on nucleotide level is more than 99.3%. When the gene encoding the mitochondrial protein of Tibetan horses was analyzed, we found that NADH6 has higher non-synonymous mutation rate in all of three Tibetan horses. This implies that NADH6 may play a role in Tibetan horses＇ high altitude adaptation. NADH6 is one of the subunits of the complex I in the respiratory chain. Furthermore, 7 D-loop sequences of Tibetan horse from different areas were sequenced, and the phylogeny tree was constructed to study the origin and evolutionary history of Tibetan horses. The result showed that the genetic diverse was high among Tibetan horses. All of Tibetan horses from Naqu were clustered into one clade, and Tibetan horses from Zhongdian and Deqin were clustered into others clades. The first molecular evidence of Tibetan horses indicated in this study is that Tibetan horse population might have multiple origins.展开更多
Objective: Highland natives adapt well to the hypoxic environment at high altitude(HA). Several genes have been reported to be linked to HA adaptation. Previous studies showed that the endothelial nitric oxide synthas...Objective: Highland natives adapt well to the hypoxic environment at high altitude(HA). Several genes have been reported to be linked to HA adaptation. Previous studies showed that the endothelial nitric oxide synthase(ENOS) G894 T polymorphism contributed to the physiology and pathophysiology of humans at HA by regulating the production of NO. In this meta-analysis, we evaluate the association between the ENOS G894 T polymorphism and HA adaptation through analyzing the published data. Methods: We searched all relevant literature about the ENOS G894 T polymorphism and HA adaptation in Pub Med, Medline, and Embase before Step 2015. A random-effects model was applied(Revman 5.0), and study quality was assessed in duplicate. Six studies with 634 HA native cases and 621 low-altitude controls were included in this meta-analysis. Results: From the results, we observed that the wild-type allele G was significantly overrepresented in the HA groups(OR=1.85; 95% CI, 1.47–2.33; P<0.0001). In addition, the GG genotype was significantly associated with HA adaptation(OR=1.99; 95% CI, 1.54–2.57; P<0.0001). Conclusion: Our results showed that in 894 G allele carriers, the GG genotype might be a beneficial factor for HA adaptation through enhancing the level of NO. However, more studies were needed to confirm our findings due to the limited sample size.展开更多
The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene...The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 （histone acetyltransferase p300）, we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide （NO） concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.展开更多
The relationship between acute high altitude response (AHAR), cardiac function injury, and high altitude de-adaptation response (HADAR) was assessed. Cardiac function indicators were assessed for 96 men (18 - 35 years...The relationship between acute high altitude response (AHAR), cardiac function injury, and high altitude de-adaptation response (HADAR) was assessed. Cardiac function indicators were assessed for 96 men (18 - 35 years old) deployed into a high altitude (3700 - 4800 m) environment requiring intense physical activity. The subjects were divided into 3 groups based on AHAR at high altitude: severe AHAR (n = 24), mild to moderate AHAR (Group B, n = 47) and non-AHAR (Group C, 25);and based on HADAR: severe HADAR (Group E, n = 19), mild to moderate HADAR (Group F, n = 40) and non-HADAR (Group G, n = 37) after return to lower altitude (1,500 m). Cardiac function indicators were measured after 50 days at high altitude and at 12 h, 15 days, and 30 days after return to lower altitude. Controls were 50 healthy volunteers (Group D, n = 50) at 1500 m. Significant differences were observed in cardiac function indicators among groups A, B, C, and D. AHAR score was positively correlated with HADAR score (r = 0.863, P < 0.001). Significant differ- ences were also observed in cardiac function indicators among groups D, E, F, and G, 12 h and15 days after return to lower altitude. There were no significant differences in cardiac function indicators among the groups, 30 days after return to lower altitude, compared to group D. The results indicated that the severity of HADAR is associated with the severity of AHAR and cardiac injury, and prolonged recovery.展开更多
Over the last several hundred years,donkeys have adapted to high-altitude conditions on the Tibetan Plateau.Interestingly,the kiang,a closely related equid species,also inhabits this region.Previous reports have demon...Over the last several hundred years,donkeys have adapted to high-altitude conditions on the Tibetan Plateau.Interestingly,the kiang,a closely related equid species,also inhabits this region.Previous reports have demonstrated the importance of specific genes and adaptive introgression in divergent lineages for adaptation to hypoxic conditions on the Tibetan Plateau.Here,we assessed whether donkeys and kiangs adapted to the Tibetan Plateau via the same or different biological pathways and whether adaptive introgression has occurred.We assembled a de novo genome from a kiang individual and analyzed the genomes of five kiangs and 93 donkeys(including 24 from the Tibetan Plateau).Our analyses suggested the existence of a strong hard selective sweep at the EPAS1 locus in kiangs.In Tibetan donkeys,however,another gene,i.e.,EGLN1,was likely involved in their adaptation to high altitude.In addition,admixture analysis found no evidence for interspecific gene flow between kiangs and Tibetan donkeys.Our findings indicate that despite the short evolutionary time scale since the arrival of donkeys on the Tibetan Plateau,as well as the existence of a closely related species already adapted to hypoxia,Tibetan donkeys did not acquire adaptation via admixture but instead evolved adaptations via a different biological pathway.展开更多
As human beings ascend to high altitude,a number of reactions may occur against hypoxic injuries.These hypoxic responses are related to intake,transportation and utility of the oxygen.As a crucial subcellular organell...As human beings ascend to high altitude,a number of reactions may occur against hypoxic injuries.These hypoxic responses are related to intake,transportation and utility of the oxygen.As a crucial subcellular organelle of oxygen utility,mitochondrion is a central link of high altitude acclimatization,adaptation and mountain sicknesses.In this review,we discussed the recent advances in researches on hypoxic mitochondrial responses at high altitude.展开更多
Sheep were domesticated in the Fertile Crescent and then spread globally,where they have been encountering various environmental conditions.The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau ...Sheep were domesticated in the Fertile Crescent and then spread globally,where they have been encountering various environmental conditions.The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau over the past 3000 years.To explore genomic variants associated with high-altitude adaptation in Tibetan sheep,we analyzed Illumina short-reads of 994 whole genomes representing∼60 sheep breeds/populations at varied altitudes,PacBio High fidelity(HiFi)reads of 13 breeds,and 96 transcriptomes from 12 sheep organs.Association testing between the inhabited altitudes and 34,298,967 variants was conducted to investigate the genetic architecture of altitude adaptation.Highly accurate HiFi reads were used to complement the current ovine reference assembly at the most significantly associatedβ-globin locus and to validate the presence of two haplotypes A and B among 13 sheep breeds.The haplotype A carried two homologous gene clusters:(1)HBE1,HBE2,HBB-like,and HBBC,and(2)HBE1-like,HBE2-like,HBB-like,and HBB;while the haplotype B lacked the first cluster.The high-altitude sheep showed highly frequent or nearly fixed haplotype A,while the low-altitude sheep dominated by haplotype B.We further demonstrated that sheep with haplotype A had an increased hemoglobin–O_(2) affinity compared with those carrying haplotype B.Another highly associated genomic region contained the EGLN1 gene which showed varied expression between high-altitude and low-altitude sheep.Our results provide evidence that the rapid adaptive evolution of advantageous alleles play an important role in facilitating the environmental adaptation of Tibetan sheep.展开更多
Microblade assemblages are among the most common prehistoric archaeological materials found on the Tibetan Plateau(TP)and are thought to indicate large scale migration to and settlement of the TP.Few microblade sites,...Microblade assemblages are among the most common prehistoric archaeological materials found on the Tibetan Plateau(TP)and are thought to indicate large scale migration to and settlement of the TP.Few microblade sites,however,have been systematically excavated,especially in the remotest,highest-elevation regions of the TP.The timing of the large-scale arrival,spread,and permanent settlement of people on the TP therefore remains controversial.In this paper,we report on a recently excavated site,Locality 3 of the Nwya Devu Site(ND3),located at 4600 meters above sea level(masl),near the shore of Ngoin Lake,on the interior TP.Our analyses reveal a fairly typical microblade technological orientation and two types of microblade cores:wedge-shaped and semi-conical,which are similar to those found throughout North China.Using Optically Stimulated Luminescence(OSL)dating and AMS^(14)C dating,the age of ND3 ranges from 11 to 10 ka.This date range indicates ND3 is the oldest microblade site yet recorded in the remote,high-elevation regions of the TP and thus provides important information about when and how hunter-gatherers using microblades began exploiting the higher altitudes of the TP.Taken together,studies at ND3 and throughout the TP suggest that a microblade adaptation is associated with the first prolonged human occupation of the plateau and that microblades played a significant role in mediating the risks and facilitating the mobility necessary to permanently inhabit the TP.展开更多
Evolutionary convergence is one of the most striking examples of adaptation driven by natural selection.However, genomic evidence for convergent adaptation to extreme environments remains scarce.Here, we assembled ref...Evolutionary convergence is one of the most striking examples of adaptation driven by natural selection.However, genomic evidence for convergent adaptation to extreme environments remains scarce.Here, we assembled reference genomes of two alpine plants, Saussurea obvallata(Asteraceae)and Rheum alexandrae(Polygonaceae), with 37,938 and 61,463 annotated protein-coding genes. By integrating an additional five alpine genomes,we elucidated genomic convergence underlying high-altitude adaptation in alpine plants. Our results detected convergent contractions of diseaseresistance genes in alpine genomes, which might be an energy-saving strategy for surviving in hostile environments with only a few pathogens present.We identified signatures of positive selection on a set of genes involved in reproduction and respiration(e.g., MMD1, NBS1, and HPR), and revealed signatures of molecular convergence on genes involved in self-incompatibility, cell wall modification,DNA repair and stress resistance, which may underlie adaptation to extreme cold, high ultraviolet radiation and hypoxia environments. Incorporating transcriptomic data, we further demonstrated that genes associated with cuticular wax and flavonoid biosynthetic pathways exhibit higher expression levels in leafy bracts, shedding light on the genetic mechanisms of the adaptive “greenhouse” morphology. Our integrative data provide novel insights into convergent evolution at a high-taxonomic level,aiding in a deep understanding of genetic adaptation to complex environments.展开更多
Mean hemoglobin(Hb) concentration of about 3 500 subjects derived from 17 studies of Himalayan highlanders(Tibetans, Sherpas, and Ladakhis) was compared with lowlanders(Chinese Han, Indian Tamils) lived in the Himalay...Mean hemoglobin(Hb) concentration of about 3 500 subjects derived from 17 studies of Himalayan highlanders(Tibetans, Sherpas, and Ladakhis) was compared with lowlanders(Chinese Han, Indian Tamils) lived in the Himalayas, and European climbers during Everest expeditions as well as Andean natives. The results found that Hb concentration in Himalayan highlanders was systemically lower than those reported for Andean natives and lowland immigrants. These comparative data demonstrated that a healthy native population may successfully reside at high altitude without a significant elevation in Hb, and the lower Hb levels of Himalayan highlanders than those of migrated lowlanders and Andean natives are an example of favourable adaptation over the generations. In addition, excessive polycythemia has frequently been used as a marker of chronic mountain sickness(CMS). Altitude populations who have a higher Hb concentration also have a higher incidence of CMS. The low Hb in Himalayans suggested as showing adaptation over many generations in Tibetan stock. Recent work in Tibet, suggested that Tibetans there may have adapted to high altitude as a result of evolutionary pressure selecting for genes which give an advantage at altitude. All of the population genomic and statistical analysis indicated that EPAS1 and EGLN1 are mostly likely responsible for high altitude adaptation and closely related to low Hb concentration in Tibetans. These data supported the hypothesis that Himalayan highlanders have evolved a genetically different erythropoietic response to chronic hypoxia by virtue of their much longer exposure to high altitude.展开更多
Maca （Lepidium meyenii Walp, 2n = 8x = 64）, belonging to the Brassicaceae family, is an economic plant cultivated in the central Andes sierra in Peru （4000-4500 m）. Considering that the rapid uplift of the central...Maca （Lepidium meyenii Walp, 2n = 8x = 64）, belonging to the Brassicaceae family, is an economic plant cultivated in the central Andes sierra in Peru （4000-4500 m）. Considering that the rapid uplift of the central Andes occurred 5-10 million years ago （Ma）, an evolutionary question arises regarding how plants such as maca acquire high-altitude adaptation within a short geological period. Here, we report the high-quality genome assembly of maca, in which two closely spaced maca-specific whole-genome duplications （WGDs; ~6.7 Ma） were identified. Comparative genomic analysis between maca and closely related Brassicaceae species revealed expansions of maca genes and gene families involved in abiotic stress response, hormone signaling pathway, and secondary metabolite biosynthesis via WGDs. The retention and subsequent functional divergence of many duplicated genes may account for the morphological and physiological changes （i.e., small leaf shape and self-fertility） in maca in a high-altitude environment. In addition, some duplicated maca genes were identified with functions in morphological adaptation （i.e., LEAF CURLING RESPONSIVENESS） and abiotic stress response （i.e., GL YClNE-RICH RNA-BINDING PROTEINS and DNA-DAMAGE-REPAIR/TOLERATION2） under positive selection. Collectively, the maca genome provides use- ful information to understand the important roles of WGDs in the high-altitude adaptation of plants in the Andes.展开更多
Humans have been exposed to many environmental challenges since their evolutionary origins in Africa and subsequent migrations to the rest of the world. A severe environmental challenge to human migrants was hypoxia c...Humans have been exposed to many environmental challenges since their evolutionary origins in Africa and subsequent migrations to the rest of the world. A severe environmental challenge to human migrants was hypoxia caused by low barometric oxygen pressure at high altitudes. Several genome-wide scans have elucidated the genetic basis of human high-altitude adaptations.However, the dearth of functional variant information has led to the successful association of only a few candidate genes. In the present study, we employed a candidate gene approach and re-sequenced the EDAR locus in 45 Tibetan individuals to identify mutations involved in hypoxia adaptation. We identified 10 and five quantitative trait-associated mutations for oxygen saturation (SaO_2) and blood platelet count, respectively, at the EDAR locus. Among these, rs10865026 and rs3749110 (associated with SaO_2 and platelet count, respectively) were identified as functional candidate targets. These data demonstrate that EDAR has undergone natural selection in recent human history and indicate an important role of EDAR variants in Tibetan high-altitude adaptations.展开更多
Blood oxygen saturation(SpO_(2))is a key indicator of oxygen availability in the body.It is known that a low SpO_(2)at high altitude is associated with morbidity and mortality risks due to physiological hypoxemia.Prev...Blood oxygen saturation(SpO_(2))is a key indicator of oxygen availability in the body.It is known that a low SpO_(2)at high altitude is associated with morbidity and mortality risks due to physiological hypoxemia.Previously,it was proposed that the lowlander immigrants living at high altitude should have a lower SpO_(2)level compared to the highlander natives,but this proposal has not been rigorously tested due to the lack of data from the lowlander immigrants living at high altitude.In this study,we compared arterial oxygen saturation of 5929 Tibetan natives and 1034 Han Chinese immigrants living at altitudes ranging from 1120 m to 5020 m.Unexpectedly,the Han immigrants had a higher SpO_(2)than the Tibetan natives at the same high altitudes.At the same time,there is a higher prevalence of chronic mountain sickness in Han than in Tibetans at the same altitude.This result suggests that the relatively higher SpO_(2)level of the acclimatized Han is associated with a physiological cost,and the SpO_(2)level of Tibetans tends to be sub-optimal.Consequently,SpO_(2)alone is not a robust indicator of physiological performance at high altitude.展开更多
基金supported by the National Natural Science Foundation of China (No. 31501860 to Xiaolong TANG, No. 31272313 and No. 31472005 to Qiang CHEN) Fundamental Research Funds for the Central Universities (lzujbky-2017-150 to Xiaolong TANG)Natural Science Foundation of Gansu Province: 1506RJYA243
文摘Poikilothermic animals living in high-altitude environments can be greatly affected by the anaerobic metabolism and lactate recycling, which are catalyzed by an enzyme called lactate dehydrogenase(LDH). However, the function and possible regulatory mechanisms of their anaerobic glycolysis remained elusive. We compared the difference in LDH between a native high-altitude(4 353 m) lizard, Phrynocephalus erythrurus, and a closely related species, Phrynocephalus przewalskii that lives in intermediate altitude environment(1 400 m). The activity of LDH, the concentration of lactate, the distribution of isoenzyme, and the mRNA amounts of Ldh-A and Ldh-B were determined. In cardiac muscle, the lactate-forming activity of P. erythrurus in LDH was higher than of P. przewalskii LDH at all three temperatures tested(10 °C, 25 °C and 35 °C), while lactate-oxidation activity of LDH was significantly different between the two species only at 25 °C and 35 °C. In skeletal muscle, both lactate-forming and lactate-oxidation rates of P. erythrurus were lower than that of P. przewalskii. There was a higher proportion of H subunit and a significantly higher expression of Ldh-B, with a concomitant decrease of lactate concentration in P. erythrurus. These results indicate that P. erythrurus may have a strong potential for anaerobic metabolism, which is likely adapted to the hypoxic environment at high altitudes. Furthermore, P. erythrurus is capable of oxidizing more lactate than P. przewalskii. The Ldh-A cDNA of the two species consists of a 999 bp open reading frame(ORF), which encodes 332 amino acids, while Ldh-B cDNA consists of a 1 002 bp ORF encoding 333 amino acids. LDHA has the same amino acid sequence between the two species, but three amino acid substitutions(V12 I, N21S and N318K) were observed in LDHB. Structure analysis of LDH indicated that the substitutions of residues Val12 and Asp21 in P. erythrurus could be responsible for the highaltitude adaptation. The LDH characteristics of LDH in P. erythrurus suggest unique adaptation strategies of anaerobic metabolism in hypoxia and cold environments at high altitudes for poikilothermic animals.
基金This work was supported by a grant from Special Foundation of President of the Chinese Academy of Sciences & the Grant of Sub-project of National Basic Research Program of China (No. 2006CB504103).
文摘To investigate genetic mechanisms of high altitude adaptations of animals living in the Tibetan Plateau, three mitochondrial genomes （mt-genome） of Tibetan horses living in Naqu （4,500 m） of Tibetan, Zhongdian （3,300 m） and Deqin （3,100 m） of Yunnan province were sequenced. The structures and lengths of these three mt-genomes are similar to the Cheju horse, which is related to Tibetan horses, but little shorter than the Swedish horse. The pair-wise identity of these three horses on nucleotide level is more than 99.3%. When the gene encoding the mitochondrial protein of Tibetan horses was analyzed, we found that NADH6 has higher non-synonymous mutation rate in all of three Tibetan horses. This implies that NADH6 may play a role in Tibetan horses＇ high altitude adaptation. NADH6 is one of the subunits of the complex I in the respiratory chain. Furthermore, 7 D-loop sequences of Tibetan horse from different areas were sequenced, and the phylogeny tree was constructed to study the origin and evolutionary history of Tibetan horses. The result showed that the genetic diverse was high among Tibetan horses. All of Tibetan horses from Naqu were clustered into one clade, and Tibetan horses from Zhongdian and Deqin were clustered into others clades. The first molecular evidence of Tibetan horses indicated in this study is that Tibetan horse population might have multiple origins.
基金supported by the National Natural Science Foundation of China(81372125)
文摘Objective: Highland natives adapt well to the hypoxic environment at high altitude(HA). Several genes have been reported to be linked to HA adaptation. Previous studies showed that the endothelial nitric oxide synthase(ENOS) G894 T polymorphism contributed to the physiology and pathophysiology of humans at HA by regulating the production of NO. In this meta-analysis, we evaluate the association between the ENOS G894 T polymorphism and HA adaptation through analyzing the published data. Methods: We searched all relevant literature about the ENOS G894 T polymorphism and HA adaptation in Pub Med, Medline, and Embase before Step 2015. A random-effects model was applied(Revman 5.0), and study quality was assessed in duplicate. Six studies with 634 HA native cases and 621 low-altitude controls were included in this meta-analysis. Results: From the results, we observed that the wild-type allele G was significantly overrepresented in the HA groups(OR=1.85; 95% CI, 1.47–2.33; P<0.0001). In addition, the GG genotype was significantly associated with HA adaptation(OR=1.99; 95% CI, 1.54–2.57; P<0.0001). Conclusion: Our results showed that in 894 G allele carriers, the GG genotype might be a beneficial factor for HA adaptation through enhancing the level of NO. However, more studies were needed to confirm our findings due to the limited sample size.
基金supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13010000)the National Natural Science Foundation of China(91631306 to BS,31671329 to XQ,31460287 to Ou,31501013 to HZ,and 31360032 to CC)+2 种基金the National 973 program(2012CB518202 to TW)the State Key Laboratory of Genetic Resources and Evolution(GREKF15-05,GREKF16-04)the Zhufeng Scholar Program of Tibetan University
文摘The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 （histone acetyltransferase p300）, we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide （NO） concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.
文摘The relationship between acute high altitude response (AHAR), cardiac function injury, and high altitude de-adaptation response (HADAR) was assessed. Cardiac function indicators were assessed for 96 men (18 - 35 years old) deployed into a high altitude (3700 - 4800 m) environment requiring intense physical activity. The subjects were divided into 3 groups based on AHAR at high altitude: severe AHAR (n = 24), mild to moderate AHAR (Group B, n = 47) and non-AHAR (Group C, 25);and based on HADAR: severe HADAR (Group E, n = 19), mild to moderate HADAR (Group F, n = 40) and non-HADAR (Group G, n = 37) after return to lower altitude (1,500 m). Cardiac function indicators were measured after 50 days at high altitude and at 12 h, 15 days, and 30 days after return to lower altitude. Controls were 50 healthy volunteers (Group D, n = 50) at 1500 m. Significant differences were observed in cardiac function indicators among groups A, B, C, and D. AHAR score was positively correlated with HADAR score (r = 0.863, P < 0.001). Significant differ- ences were also observed in cardiac function indicators among groups D, E, F, and G, 12 h and15 days after return to lower altitude. There were no significant differences in cardiac function indicators among the groups, 30 days after return to lower altitude, compared to group D. The results indicated that the severity of HADAR is associated with the severity of AHAR and cardiac injury, and prolonged recovery.
基金supported by the National Natural Science Foundation of China (31621062)Strategic Priority Research Program of the Chinese Academy of Sciences (XDA2004010302)+4 种基金Second Tibetan Plateau Scientific Expedition and Research (STEP)Program (2019QZKK05010703)supported by the National Natural Science Foundation of China (91731304, 31822048)Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13020600)Qinghai Department of Science and Technology Major ProjectState Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan,Yunnan University(2018KF001)supported by the Animal Branch of the Germplasm Bank of Wild Species,Chinese Academy of Sciences (Large Research Infrastructure Funding)
文摘Over the last several hundred years,donkeys have adapted to high-altitude conditions on the Tibetan Plateau.Interestingly,the kiang,a closely related equid species,also inhabits this region.Previous reports have demonstrated the importance of specific genes and adaptive introgression in divergent lineages for adaptation to hypoxic conditions on the Tibetan Plateau.Here,we assessed whether donkeys and kiangs adapted to the Tibetan Plateau via the same or different biological pathways and whether adaptive introgression has occurred.We assembled a de novo genome from a kiang individual and analyzed the genomes of five kiangs and 93 donkeys(including 24 from the Tibetan Plateau).Our analyses suggested the existence of a strong hard selective sweep at the EPAS1 locus in kiangs.In Tibetan donkeys,however,another gene,i.e.,EGLN1,was likely involved in their adaptation to high altitude.In addition,admixture analysis found no evidence for interspecific gene flow between kiangs and Tibetan donkeys.Our findings indicate that despite the short evolutionary time scale since the arrival of donkeys on the Tibetan Plateau,as well as the existence of a closely related species already adapted to hypoxia,Tibetan donkeys did not acquire adaptation via admixture but instead evolved adaptations via a different biological pathway.
基金supported by the Grants from National Natural Science Foundation of China (81071610, 81471814)
文摘As human beings ascend to high altitude,a number of reactions may occur against hypoxic injuries.These hypoxic responses are related to intake,transportation and utility of the oxygen.As a crucial subcellular organelle of oxygen utility,mitochondrion is a central link of high altitude acclimatization,adaptation and mountain sicknesses.In this review,we discussed the recent advances in researches on hypoxic mitochondrial responses at high altitude.
基金supported by the Tibetan R&D Program,China(Grant No.XZ202101ZD0001N)the China Agriculture Research System(Grant No.CARS-39)the National Natural Science Foundation of China(Grant Nos.31900313,32161143010,and 31972526).
文摘Sheep were domesticated in the Fertile Crescent and then spread globally,where they have been encountering various environmental conditions.The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau over the past 3000 years.To explore genomic variants associated with high-altitude adaptation in Tibetan sheep,we analyzed Illumina short-reads of 994 whole genomes representing∼60 sheep breeds/populations at varied altitudes,PacBio High fidelity(HiFi)reads of 13 breeds,and 96 transcriptomes from 12 sheep organs.Association testing between the inhabited altitudes and 34,298,967 variants was conducted to investigate the genetic architecture of altitude adaptation.Highly accurate HiFi reads were used to complement the current ovine reference assembly at the most significantly associatedβ-globin locus and to validate the presence of two haplotypes A and B among 13 sheep breeds.The haplotype A carried two homologous gene clusters:(1)HBE1,HBE2,HBB-like,and HBBC,and(2)HBE1-like,HBE2-like,HBB-like,and HBB;while the haplotype B lacked the first cluster.The high-altitude sheep showed highly frequent or nearly fixed haplotype A,while the low-altitude sheep dominated by haplotype B.We further demonstrated that sheep with haplotype A had an increased hemoglobin–O_(2) affinity compared with those carrying haplotype B.Another highly associated genomic region contained the EGLN1 gene which showed varied expression between high-altitude and low-altitude sheep.Our results provide evidence that the rapid adaptive evolution of advantageous alleles play an important role in facilitating the environmental adaptation of Tibetan sheep.
基金supported by the National Key Research and Development Project of China(Grant No.2021YFC1523603)the Second Tibetan Plateau Scientific Expedition and Research(Grant No.2019QZKK0601)+1 种基金the National Natural Science Foundation of China(Grant Nos.42072033&41977380)the National Social Science Foundation of China(Grant Nos.23&ZD268&21@WTK001)。
文摘Microblade assemblages are among the most common prehistoric archaeological materials found on the Tibetan Plateau(TP)and are thought to indicate large scale migration to and settlement of the TP.Few microblade sites,however,have been systematically excavated,especially in the remotest,highest-elevation regions of the TP.The timing of the large-scale arrival,spread,and permanent settlement of people on the TP therefore remains controversial.In this paper,we report on a recently excavated site,Locality 3 of the Nwya Devu Site(ND3),located at 4600 meters above sea level(masl),near the shore of Ngoin Lake,on the interior TP.Our analyses reveal a fairly typical microblade technological orientation and two types of microblade cores:wedge-shaped and semi-conical,which are similar to those found throughout North China.Using Optically Stimulated Luminescence(OSL)dating and AMS^(14)C dating,the age of ND3 ranges from 11 to 10 ka.This date range indicates ND3 is the oldest microblade site yet recorded in the remote,high-elevation regions of the TP and thus provides important information about when and how hunter-gatherers using microblades began exploiting the higher altitudes of the TP.Taken together,studies at ND3 and throughout the TP suggest that a microblade adaptation is associated with the first prolonged human occupation of the plateau and that microblades played a significant role in mediating the risks and facilitating the mobility necessary to permanently inhabit the TP.
基金supported by the Second Tibetan Plateau Scientific Expedition and Research program (2019QZKK0502)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA20050203)+3 种基金the Key Projects of the Joint Fund of the National Natural Science Foundation of China (U1802232)the Youth Innovation Promotion Association of Chinese Academy of Sciences (2019382)the Yunnan Young & Elite Talents Project (YNWR-QNBJ-2019-033)the Ten Thousand Talents Program of Yunnan Province (202005AB160005)。
文摘Evolutionary convergence is one of the most striking examples of adaptation driven by natural selection.However, genomic evidence for convergent adaptation to extreme environments remains scarce.Here, we assembled reference genomes of two alpine plants, Saussurea obvallata(Asteraceae)and Rheum alexandrae(Polygonaceae), with 37,938 and 61,463 annotated protein-coding genes. By integrating an additional five alpine genomes,we elucidated genomic convergence underlying high-altitude adaptation in alpine plants. Our results detected convergent contractions of diseaseresistance genes in alpine genomes, which might be an energy-saving strategy for surviving in hostile environments with only a few pathogens present.We identified signatures of positive selection on a set of genes involved in reproduction and respiration(e.g., MMD1, NBS1, and HPR), and revealed signatures of molecular convergence on genes involved in self-incompatibility, cell wall modification,DNA repair and stress resistance, which may underlie adaptation to extreme cold, high ultraviolet radiation and hypoxia environments. Incorporating transcriptomic data, we further demonstrated that genes associated with cuticular wax and flavonoid biosynthetic pathways exhibit higher expression levels in leafy bracts, shedding light on the genetic mechanisms of the adaptive “greenhouse” morphology. Our integrative data provide novel insights into convergent evolution at a high-taxonomic level,aiding in a deep understanding of genetic adaptation to complex environments.
基金supported by the"973"National Basic Research Program(2012 CB 518202,and"Pre-973"National Basic Research Program(2012 CB 722506),PRC
文摘Mean hemoglobin(Hb) concentration of about 3 500 subjects derived from 17 studies of Himalayan highlanders(Tibetans, Sherpas, and Ladakhis) was compared with lowlanders(Chinese Han, Indian Tamils) lived in the Himalayas, and European climbers during Everest expeditions as well as Andean natives. The results found that Hb concentration in Himalayan highlanders was systemically lower than those reported for Andean natives and lowland immigrants. These comparative data demonstrated that a healthy native population may successfully reside at high altitude without a significant elevation in Hb, and the lower Hb levels of Himalayan highlanders than those of migrated lowlanders and Andean natives are an example of favourable adaptation over the generations. In addition, excessive polycythemia has frequently been used as a marker of chronic mountain sickness(CMS). Altitude populations who have a higher Hb concentration also have a higher incidence of CMS. The low Hb in Himalayans suggested as showing adaptation over many generations in Tibetan stock. Recent work in Tibet, suggested that Tibetans there may have adapted to high altitude as a result of evolutionary pressure selecting for genes which give an advantage at altitude. All of the population genomic and statistical analysis indicated that EPAS1 and EGLN1 are mostly likely responsible for high altitude adaptation and closely related to low Hb concentration in Tibetans. These data supported the hypothesis that Himalayan highlanders have evolved a genetically different erythropoietic response to chronic hypoxia by virtue of their much longer exposure to high altitude.
文摘Maca （Lepidium meyenii Walp, 2n = 8x = 64）, belonging to the Brassicaceae family, is an economic plant cultivated in the central Andes sierra in Peru （4000-4500 m）. Considering that the rapid uplift of the central Andes occurred 5-10 million years ago （Ma）, an evolutionary question arises regarding how plants such as maca acquire high-altitude adaptation within a short geological period. Here, we report the high-quality genome assembly of maca, in which two closely spaced maca-specific whole-genome duplications （WGDs; ~6.7 Ma） were identified. Comparative genomic analysis between maca and closely related Brassicaceae species revealed expansions of maca genes and gene families involved in abiotic stress response, hormone signaling pathway, and secondary metabolite biosynthesis via WGDs. The retention and subsequent functional divergence of many duplicated genes may account for the morphological and physiological changes （i.e., small leaf shape and self-fertility） in maca in a high-altitude environment. In addition, some duplicated maca genes were identified with functions in morphological adaptation （i.e., LEAF CURLING RESPONSIVENESS） and abiotic stress response （i.e., GL YClNE-RICH RNA-BINDING PROTEINS and DNA-DAMAGE-REPAIR/TOLERATION2） under positive selection. Collectively, the maca genome provides use- ful information to understand the important roles of WGDs in the high-altitude adaptation of plants in the Andes.
基金supported by the National Natural Science Foundation of China (91131905, 30890030)Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13020500)Weng Hongwu Original Scientific Research Foundation, Peking University
文摘Humans have been exposed to many environmental challenges since their evolutionary origins in Africa and subsequent migrations to the rest of the world. A severe environmental challenge to human migrants was hypoxia caused by low barometric oxygen pressure at high altitudes. Several genome-wide scans have elucidated the genetic basis of human high-altitude adaptations.However, the dearth of functional variant information has led to the successful association of only a few candidate genes. In the present study, we employed a candidate gene approach and re-sequenced the EDAR locus in 45 Tibetan individuals to identify mutations involved in hypoxia adaptation. We identified 10 and five quantitative trait-associated mutations for oxygen saturation (SaO_2) and blood platelet count, respectively, at the EDAR locus. Among these, rs10865026 and rs3749110 (associated with SaO_2 and platelet count, respectively) were identified as functional candidate targets. These data demonstrate that EDAR has undergone natural selection in recent human history and indicate an important role of EDAR variants in Tibetan high-altitude adaptations.
基金Funding This study was funded by grants from the National Natural Science Foundation of China(NSFC)(32288101 and 91631306 to BS3217040584 and 32000390 to YH,32070578 and U22A20340 to XQ,and 32170629 to HZ)+3 种基金the Youth Innovation Promotion Association of CAS(to YH)the Science and Technology General Program of Yunnan Province(202301AW070010 and 202001AT070110 to YH)the Provincial Key Research,Development and Translational Program of Tibetan Autonomous Region of China(XZ202201ZY0035G to XQ)the State Key Laboratory of Genetic Resources and Evolution(GREKF22-15 to HZ).
文摘Blood oxygen saturation(SpO_(2))is a key indicator of oxygen availability in the body.It is known that a low SpO_(2)at high altitude is associated with morbidity and mortality risks due to physiological hypoxemia.Previously,it was proposed that the lowlander immigrants living at high altitude should have a lower SpO_(2)level compared to the highlander natives,but this proposal has not been rigorously tested due to the lack of data from the lowlander immigrants living at high altitude.In this study,we compared arterial oxygen saturation of 5929 Tibetan natives and 1034 Han Chinese immigrants living at altitudes ranging from 1120 m to 5020 m.Unexpectedly,the Han immigrants had a higher SpO_(2)than the Tibetan natives at the same high altitudes.At the same time,there is a higher prevalence of chronic mountain sickness in Han than in Tibetans at the same altitude.This result suggests that the relatively higher SpO_(2)level of the acclimatized Han is associated with a physiological cost,and the SpO_(2)level of Tibetans tends to be sub-optimal.Consequently,SpO_(2)alone is not a robust indicator of physiological performance at high altitude.
