Nitric oxide(NO)is a key vasodilator that regulates vascular pressure and blood flow.Tibetans have developed a"blunted"mechanism for regulating NO levels at high altitude,with GTP cyclohydrolase 1(GCH1)ident...Nitric oxide(NO)is a key vasodilator that regulates vascular pressure and blood flow.Tibetans have developed a"blunted"mechanism for regulating NO levels at high altitude,with GTP cyclohydrolase 1(GCH1)identified as a key candidate gene.Here,we present comprehensive genetic and functional analyses of GCH1,which exhibits strong Darwinian positive selection in Tibetans.We show that Tibetan-enriched GCH1 variants down-regulate its expression in the blood of Tibetans.Based on this observation,we generate the heterozygous Gch1 knockout(Gch1^(+/-))mouse model to simulate its downregulation in Tibetans.We find that under prolonged hypoxia,the Gch1^(+/-)mice have relatively higher blood NO and blood oxygen saturation levels compared with the wild-type(WT)controls,providing better oxygen supplies to the cardiovascular and pulmonary systems.Markedly,hypoxia-induced cardiac hypertrophy and pulmonary remodeling are significantly attenuated in the Gch1^(^(+/-))mice compared with the WT controls,likely due to the adaptive changes in molecular regulations related to metabolism,inflammation,circadian rhythm,extracellular matrix,and oxidative stress.This study sheds light on the role of GCH1 in regulating blood NO,contributing to the physiological adaptation of the cardiovascular and pulmonary systems in Tibetans at high altitude.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 settlement of the Tibetan Plateau epitomizes human adaptation to a high-altitude environment that poses great challenges to human activity.Here,we reconstruct a 4000-year maternal genetic history of Tibetans using...The settlement of the Tibetan Plateau epitomizes human adaptation to a high-altitude environment that poses great challenges to human activity.Here,we reconstruct a 4000-year maternal genetic history of Tibetans using 128 ancient mitochondrial genome data from 37 sites in Xizang.The phylogeny of haplotypes M9a1a,M9a1b,D4g2,G2a’c,and D4i show that ancient Tibetans share the most recent common ancestor with ancient Middle and Upper Yellow River populations around the Early and Middle Holocene.In addition,the connections between Tibetans and Northeastern Asians vary over the past 4000 years,with a stronger matrilineal connection between the two during 4000 BPe3000 BP,and a weakened connection after 3000 BP,that are coincident with climate change,followed by a reinforced connection after the Tubo period(1400 BPe1100 BP).Besides,an over 4000-year matrilineal continuity is observed in some of the maternal lineages.We also find the maternal genetic structure of ancient Tibetans is correlated to the geography and interactions between ancient Tibetans and ancient Nepal and Pakistan populations.Overall,the maternal genetic history of Tibetans can be characterized as a long-term matrilineal continuity with frequent internal and external population interactions that are dynamically shaped by geography,climate changes,as well as historical events.展开更多
People living on the high plateaus of the world have long fascinated biological anthropologists and geneticists because they live in ＂thin air＂ and epitomize an extreme of human biological adaptation.
SIXTY-EIGHT years ago, the Song of the Erlang Mountain was a smash hit all over China. It is an ode to the heroic builders of the highway between Sichuan and Tibet, which cuts through towering mountains and spans bill...SIXTY-EIGHT years ago, the Song of the Erlang Mountain was a smash hit all over China. It is an ode to the heroic builders of the highway between Sichuan and Tibet, which cuts through towering mountains and spans billowy rivers.展开更多
Costume.The clothes and accessories of the Tibetans are colorful and varied.The main garments are the traditional Tibetan robe,featuring long sleeves,a wide waist and buttons on the right.In agricultural regions and t...Costume.The clothes and accessories of the Tibetans are colorful and varied.The main garments are the traditional Tibetan robe,featuring long sleeves,a wide waist and buttons on the right.In agricultural regions and towns and cities people wear Tibetan robes,jackets and shirts.Most Tibetan robes are made pulu,and some robes are made of woolen cloth .Tibetan robes have a bigger right front and a smaller left front.and some have a button on the right armpit.They展开更多
July 20, 2010 was a happy day for Nima Zhuoga, of Jiangcun Village in Quxu County, Tibet. That is when she was moving to her new house. Many fellow villagers came to offer congratulations. Zhuoga says： ＂Our new home...July 20, 2010 was a happy day for Nima Zhuoga, of Jiangcun Village in Quxu County, Tibet. That is when she was moving to her new house. Many fellow villagers came to offer congratulations. Zhuoga says： ＂Our new home is a two-storied,展开更多
EDITOR＇S NOTE： On June 15-29, 2005 Toriumi Yoshiro, a reporter of the Sankei Shimbun of Japan, made a reporting tour of Tibet and Gannan Tibetan Autonomous Prefecture of Gansu Province. After returning home, he publ...EDITOR＇S NOTE： On June 15-29, 2005 Toriumi Yoshiro, a reporter of the Sankei Shimbun of Japan, made a reporting tour of Tibet and Gannan Tibetan Autonomous Prefecture of Gansu Province. After returning home, he published a series of reports in the Sankei Shimbun. Following are three of his reports.展开更多
Ethnic Tibetans speak and write by using their own language and characters. This language belongs to the Tibet-Burman phylum in the Sino-Tibetan language family. In over 1400 years of recorded history,ethnic Tibetans ...Ethnic Tibetans speak and write by using their own language and characters. This language belongs to the Tibet-Burman phylum in the Sino-Tibetan language family. In over 1400 years of recorded history,ethnic Tibetans have been enriched by the profuse contents of their archaic books that make us gasp in admiration.展开更多
EDITOR＇S NOTE： From August 11 through 21, 2005, Fernando Garcia, a reporter of Spain＇s ABC newspaper, undertook a reporting tour of Tibet at the invitation of China. After he returned home, Interviu, a Spanish maga...EDITOR＇S NOTE： From August 11 through 21, 2005, Fernando Garcia, a reporter of Spain＇s ABC newspaper, undertook a reporting tour of Tibet at the invitation of China. After he returned home, Interviu, a Spanish magazine, carried his story tiffed Viejo Tibet, Nuevos Tibetanos. Following is his story translated from its Chinese version.展开更多
Chawalung is a small town lying on a transport hub linking Zayu of Tibet with Gongshan of Yunnan Province. It is home to theTibetan, Dulong, Nu, Lili, Naxi and some other ethnic minorities. They maintain a varied folk...Chawalung is a small town lying on a transport hub linking Zayu of Tibet with Gongshan of Yunnan Province. It is home to theTibetan, Dulong, Nu, Lili, Naxi and some other ethnic minorities. They maintain a varied folklore that finds concentrated expression in their diet, living habits, clothing, wedding ceremonies and religious beliefs.展开更多
EDITOR'S NOTE: Longyearbyen, capital of the Svalbard Islands, entered its annualprolonged period of darkness on October9,2001.The sun was not due to rise againuntil March 8, 2002.During the five-month-long period ...EDITOR'S NOTE: Longyearbyen, capital of the Svalbard Islands, entered its annualprolonged period of darkness on October9,2001.The sun was not due to rise againuntil March 8, 2002.During the five-month-long period of perpetual night,people livingin the northernmost human settlement see only stars, snow and ice. In this part of theworld, however, there are four students from the Tibet Autonomous Regionjoint-venture school.展开更多
In autumn of 1946 Tsering Wangdo,then just 12 years old, went to India to study. That was 60 years ago when I interviewed him in 2006. Obviously,the young man has gone but the
基金funded by grants from the National Natural Science Foundation of China(32288101 and 91631306 to B.S32170632 and 32000390 to Y.H.32400503 to Y.G.)Major Scientific Project of Yunnan Province(202305AH340007 to B.S.)+4 种基金Yunnan Revitalization Talent Support Program Science&Technology Champion Project(202005AB160004 to B.S.)Yunnan Revitalization Talent Support Program Innovation Team(202405AS350008)Yunnan Scientist Workshops(to B.S.)the Youth Innovation Promotion Association of CAS(to Y.H.),the Science and Technology General Program of Yunnan Province(202301AW070010 and 202001AT070110 to Y.H.)and the Provincial Key Research,Development,and Translational Program(XZ202101ZY0009G to Baima.).
文摘Nitric oxide(NO)is a key vasodilator that regulates vascular pressure and blood flow.Tibetans have developed a"blunted"mechanism for regulating NO levels at high altitude,with GTP cyclohydrolase 1(GCH1)identified as a key candidate gene.Here,we present comprehensive genetic and functional analyses of GCH1,which exhibits strong Darwinian positive selection in Tibetans.We show that Tibetan-enriched GCH1 variants down-regulate its expression in the blood of Tibetans.Based on this observation,we generate the heterozygous Gch1 knockout(Gch1^(+/-))mouse model to simulate its downregulation in Tibetans.We find that under prolonged hypoxia,the Gch1^(+/-)mice have relatively higher blood NO and blood oxygen saturation levels compared with the wild-type(WT)controls,providing better oxygen supplies to the cardiovascular and pulmonary systems.Markedly,hypoxia-induced cardiac hypertrophy and pulmonary remodeling are significantly attenuated in the Gch1^(^(+/-))mice compared with the WT controls,likely due to the adaptive changes in molecular regulations related to metabolism,inflammation,circadian rhythm,extracellular matrix,and oxidative stress.This study sheds light on the role of GCH1 in regulating blood NO,contributing to the physiological adaptation of the cardiovascular and pulmonary systems in Tibetans at high altitude.
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.
基金supported by the National Key R&D Program of China(2021YFC1523600)the Chinese Academy of Sciences(CAS)(YSBR-019 and XDB26000000)+3 种基金the National Natural Science Foundation of China(41925009)“Research on the roots of Chinese civilization”of Zhengzhou University(XKZDJC202006)the Tencent Foundation(through the XPLORER PRIZE),and the Howard Hughes Medical Institute(55008731)X.W.was supported by Key National Social Science Foundation of China(16ZDA144).
文摘The settlement of the Tibetan Plateau epitomizes human adaptation to a high-altitude environment that poses great challenges to human activity.Here,we reconstruct a 4000-year maternal genetic history of Tibetans using 128 ancient mitochondrial genome data from 37 sites in Xizang.The phylogeny of haplotypes M9a1a,M9a1b,D4g2,G2a’c,and D4i show that ancient Tibetans share the most recent common ancestor with ancient Middle and Upper Yellow River populations around the Early and Middle Holocene.In addition,the connections between Tibetans and Northeastern Asians vary over the past 4000 years,with a stronger matrilineal connection between the two during 4000 BPe3000 BP,and a weakened connection after 3000 BP,that are coincident with climate change,followed by a reinforced connection after the Tubo period(1400 BPe1100 BP).Besides,an over 4000-year matrilineal continuity is observed in some of the maternal lineages.We also find the maternal genetic structure of ancient Tibetans is correlated to the geography and interactions between ancient Tibetans and ancient Nepal and Pakistan populations.Overall,the maternal genetic history of Tibetans can be characterized as a long-term matrilineal continuity with frequent internal and external population interactions that are dynamically shaped by geography,climate changes,as well as historical events.
文摘People living on the high plateaus of the world have long fascinated biological anthropologists and geneticists because they live in ＂thin air＂ and epitomize an extreme of human biological adaptation.
文摘SIXTY-EIGHT years ago, the Song of the Erlang Mountain was a smash hit all over China. It is an ode to the heroic builders of the highway between Sichuan and Tibet, which cuts through towering mountains and spans billowy rivers.
文摘Costume.The clothes and accessories of the Tibetans are colorful and varied.The main garments are the traditional Tibetan robe,featuring long sleeves,a wide waist and buttons on the right.In agricultural regions and towns and cities people wear Tibetan robes,jackets and shirts.Most Tibetan robes are made pulu,and some robes are made of woolen cloth .Tibetan robes have a bigger right front and a smaller left front.and some have a button on the right armpit.They
文摘July 20, 2010 was a happy day for Nima Zhuoga, of Jiangcun Village in Quxu County, Tibet. That is when she was moving to her new house. Many fellow villagers came to offer congratulations. Zhuoga says： ＂Our new home is a two-storied,
文摘EDITOR＇S NOTE： On June 15-29, 2005 Toriumi Yoshiro, a reporter of the Sankei Shimbun of Japan, made a reporting tour of Tibet and Gannan Tibetan Autonomous Prefecture of Gansu Province. After returning home, he published a series of reports in the Sankei Shimbun. Following are three of his reports.
文摘Ethnic Tibetans speak and write by using their own language and characters. This language belongs to the Tibet-Burman phylum in the Sino-Tibetan language family. In over 1400 years of recorded history,ethnic Tibetans have been enriched by the profuse contents of their archaic books that make us gasp in admiration.
文摘EDITOR＇S NOTE： From August 11 through 21, 2005, Fernando Garcia, a reporter of Spain＇s ABC newspaper, undertook a reporting tour of Tibet at the invitation of China. After he returned home, Interviu, a Spanish magazine, carried his story tiffed Viejo Tibet, Nuevos Tibetanos. Following is his story translated from its Chinese version.
文摘Chawalung is a small town lying on a transport hub linking Zayu of Tibet with Gongshan of Yunnan Province. It is home to theTibetan, Dulong, Nu, Lili, Naxi and some other ethnic minorities. They maintain a varied folklore that finds concentrated expression in their diet, living habits, clothing, wedding ceremonies and religious beliefs.
文摘EDITOR'S NOTE: Longyearbyen, capital of the Svalbard Islands, entered its annualprolonged period of darkness on October9,2001.The sun was not due to rise againuntil March 8, 2002.During the five-month-long period of perpetual night,people livingin the northernmost human settlement see only stars, snow and ice. In this part of theworld, however, there are four students from the Tibet Autonomous Regionjoint-venture school.
文摘In autumn of 1946 Tsering Wangdo,then just 12 years old, went to India to study. That was 60 years ago when I interviewed him in 2006. Obviously,the young man has gone but the
