智力包括了逻辑推理能力、理解能力、自我意识能力、学习能力、计划能力、创造能力和解决问题等能力。智力发育存在性别差异,女性智力的成熟时间往往早于男性。然而,关于智力发育性别差异的关键基因及其分子网络机制尚不清楚。迄今为止...智力包括了逻辑推理能力、理解能力、自我意识能力、学习能力、计划能力、创造能力和解决问题等能力。智力发育存在性别差异,女性智力的成熟时间往往早于男性。然而,关于智力发育性别差异的关键基因及其分子网络机制尚不清楚。迄今为止,全基因组关联分析(Genome-Wide Association Studies,GWAS)发现了507个与智力显著相关的基因。本论文首先分析了BrainSpan人脑RNA-seq数据集中大脑在各个发育阶段的转录测序数据,发现在胚胎晚期,507个智力基因在大脑中的平均表达水平男性高于女性,而在青春期则相反。接着进一步构建了大脑中表达水平具有性别差异的智力基因的互作网络,包括胚胎晚期中男性高表达的智力基因互作网络HELP-M(intelligence genes with higher expression levels in prenatal males)、青春期女性高表达的智力基因互作网络HELP-F(intelligence genes with higher expression levels in pubertal females)。结果表明,这两个网络的关键基因均是Ep300和Ctnnb1。其中Ep300在HELP-M和HELP-F中调控了53个基因的转录,Ctnnb1在HELP-M和HELP-F中调控了45个基因转录,Ctnnb1在HELP-M以及Ep300在HELP-F中分别发挥更重要的作用。对不同发育时间的大鼠进行测序验证,发现在青春期雌性大鼠前额叶皮层中HELP-F的智力基因和关键基因Ep300、Ctnnb1表达水平显著高于雄性大鼠,并且参与了神经发育等相关生物过程。以上结果揭示了在神经发育过程中表达水平具有性别差异的智力基因网络及其关键基因。展开更多
China's Northern and Southern Dynasties period(3rd–6th centuries AD)marked a significant era of ethnic integration in northern China.However,previous ancient DNA studies have primarily focused on northern ethnic ...China's Northern and Southern Dynasties period(3rd–6th centuries AD)marked a significant era of ethnic integration in northern China.However,previous ancient DNA studies have primarily focused on northern ethnic groups,with limited research on the genetic formation of the hereditary elite family,especially considering their abundant archaeological record and clear material identity.In this study,we obtain the ancient genome of a hereditary elite family,Gao Bin(高宾,503 AD–572 AD),at 0.6473-fold coverage with 475,132 single-nucleotide polymorphisms(SNPs)on the 1240k panel.His mitochondrial haplogroup belongs to Z4 and Y-haplogroup to O1a1a2b-F2444∗.The genetic profile of Gao Bin is most similar to that of the northern Han Chinese.He can be modeled as deriving all his ancestry from Late Neolithic to Iron Age Yellow River farmers without influence from Northeast Asia,Korea,or the Mongolian Plateau.Our study sheds light on the genetic formation of hereditary elite families in the context of the Southern and Northern Dynasties ethnic integration.展开更多
乳腺癌作为全球女性发病率最高的恶性肿瘤,其预后存在显著异质性。基于癌症基因组图谱(the cancer genome atlas,TCGA)数据库,对乳腺癌患者的转录组数据进行差异分析和相关性分析,筛选出尼古丁代谢相关的差异表达基因。采用单因素Cox回...乳腺癌作为全球女性发病率最高的恶性肿瘤,其预后存在显著异质性。基于癌症基因组图谱(the cancer genome atlas,TCGA)数据库,对乳腺癌患者的转录组数据进行差异分析和相关性分析,筛选出尼古丁代谢相关的差异表达基因。采用单因素Cox回归分析和Lasso-Cox回归分析方法构建预后模型,并通过Kaplan-Meier生存曲线、ROC曲线、校准曲线及包含临床因素的列线图进行评估。使用基因表达总库(gene expressi on omnibus,GEO)中的GSE42568数据集作为外部验证集进行模型验证,并进一步开展免疫浸润分析和药物敏感性分析。结果发现,模型由10个尼古丁代谢相关基因组成,可作为乳腺癌的独立预后因素,并且高低风险组在免疫细胞浸润及药物敏感性上具有显著差异。构建的风险预后模型能够独立预测乳腺癌的预后情况,可为乳腺癌预后评估和个体化治疗提供新的分子标志物和潜在治疗靶点。展开更多
Shandong province,located in the Lower Yellow River,is one of the birthplaces of ancient Chinese civilization.However,the comprehensive genetic histories of this region have remained largely unknown until now due to a...Shandong province,located in the Lower Yellow River,is one of the birthplaces of ancient Chinese civilization.However,the comprehensive genetic histories of this region have remained largely unknown until now due to a lack of ancient human genomes.Here,we present 21 ancient genomes from Shandong dating from the Warring States period to the Northern Dynasties.Unlike the early Neolithic samples from Shandong,the historical samples are most closely related to post-Late Neolithic populations of the Middle Yellow River Basin,suggesting a population turnover in Shandong from the Neolithic Age to the Historical era.In addition,we detect a close genetic affinity between the historical samples in Shandong and present-day Han Chinese,showing long-term genetic stability in Han Chinese,at least since the Warring States period.展开更多
The Hehuang Valley,situated in the northeastern section of the Qinghai-Tibet Plateau,represents the upper reaches of the Yellow River(Fig.1A).It is a significant geographic region of origin for numerous Neolithic cult...The Hehuang Valley,situated in the northeastern section of the Qinghai-Tibet Plateau,represents the upper reaches of the Yellow River(Fig.1A).It is a significant geographic region of origin for numerous Neolithic cultures,including the Majiayao,Zongri,and Qijia cultures(Dong et al.,2013).展开更多
Yunnan in southwest China is a geographically and ethnically complex region at the intersection of southern China and Southeast Asia,and a focal point for human migrations.To clarify its maternal genetic history,we ge...Yunnan in southwest China is a geographically and ethnically complex region at the intersection of southern China and Southeast Asia,and a focal point for human migrations.To clarify its maternal genetic history,we generated 152 complete mitogenomes from 17 Yunnan archaeological sites.Our results reveal distinct genetic histories segregated by geographical regions.Maternal lineages of ancient populations from northwestern and northern Yunnan exhibit closer affinities with past and present-day populations from northern East Asia and Xizang,providing important genetic evidence for the migration and interaction of populations along the Tibetan-Yi corridor since the Neolithic.Between 5500 and 1800 years ago,central Yunnan populations maintained their internal genetic relationships,including a 7000-year-old basal lineage of the rare and widely dispersed haplogroup M61.At the Xingyi site,changes in mitochondrial DNA haplogroups occurred between the Late Neolithic and Bronze Age,with haplogroups shifting from those predominant in the Yellow River region to those predominant in coastal southern China.These results highlight the high diversity of Yunnan populations during the Neolithic to Bronze Age.展开更多
Facial morphology,a complex trait influenced by genetics,holds great significance in evolutionary research.However,due to limited fossil evidence,the facial characteristics of Neanderthals and Denisovans have remained...Facial morphology,a complex trait influenced by genetics,holds great significance in evolutionary research.However,due to limited fossil evidence,the facial characteristics of Neanderthals and Denisovans have remained largely unknown.In this study,we conduct a large-scale multi-ethnic meta-analysis of the genome-wide association study(GWAS),including 9674 East Asians and 10,115 Europeans,quantitatively assessing 78 facial traits using 3D facial images.We identify 71 genomic loci associated with facial features,including 21 novel loci.We develop a facial polygenic score(FPS)that enables the prediction of facial features based on genetic information.Interestingly,the distribution of FPSs among populations from diverse continental groups exhibits relevant correlations with observed facial features.Furthermore,we apply the FPS to predict the facial traits of seven Neanderthals and one Denisovan using ancient DNA and align predictions with the fossil records.Our results suggest that Neanderthals and Denisovans likely share similar facial features,such as a wider but shorter nose and a wider endocanthion distance.The decreased mouth width is characterized specifically in Denisovans.The integration of genomic data and facial trait analysis provides valuable insights into the evolutionary history and adaptive changes in human facial morphology.展开更多
The reconstruction of demographic history using ancient and modern genomic resources reveals extensive interactions and admixture between ancient nomadic pastoralists and the social organizations of the Chinese Centra...The reconstruction of demographic history using ancient and modern genomic resources reveals extensive interactions and admixture between ancient nomadic pastoralists and the social organizations of the Chinese Central Plain.However,the extent to which Y-chromosome genetic legacies from nomadic emperor-related ancestral lineages influence the Chinese paternal gene pool remains unclear.Here,we genotype 2717 ethnolinguistically diverse samples belonging to C2a lineages,perform whole-genome sequencing on 997 representative samples,and integrate these data with ancient genomic sequences.We reconstruct the evolutionary histories of Northern Zhou-,Qing emperor-,and pastoralist-related lineages to assess their genetic impact on modern Chinese populations.This reassembled fine-scale Ychromosome phylogeny identifies deep divergence and five Neolithic expansion events contributing differently to the formation of northern Chinese populations.Phylogeographic modeling indicates that the nomadic empires of the Northern Zhou and Qing dynasties genetically originated from the Mongolian Plateau.Phylogenetic topology and shared haplotype patterns show that three upstream ancestors of Northern Zhou(C2a1a1b1a2a1b-FGC28857),Donghu tribe(C2a1a1b1-F1756),and Qing(C2a1a3a2-F10283)emperor-related lineages expanded during the middle Neolithic,contributing significantly to genetic flow between ancient northeastern Asians and modern East Asians.Notably,this study reveals limited direct contributions of Emperor Wu of Northern Zhou’s lineages to modern East Asians.展开更多
基金supported by Sci-Tech Innovation 2030-Major Projects(No.2021ZD0200512).
文摘智力包括了逻辑推理能力、理解能力、自我意识能力、学习能力、计划能力、创造能力和解决问题等能力。智力发育存在性别差异,女性智力的成熟时间往往早于男性。然而,关于智力发育性别差异的关键基因及其分子网络机制尚不清楚。迄今为止,全基因组关联分析(Genome-Wide Association Studies,GWAS)发现了507个与智力显著相关的基因。本论文首先分析了BrainSpan人脑RNA-seq数据集中大脑在各个发育阶段的转录测序数据,发现在胚胎晚期,507个智力基因在大脑中的平均表达水平男性高于女性,而在青春期则相反。接着进一步构建了大脑中表达水平具有性别差异的智力基因的互作网络,包括胚胎晚期中男性高表达的智力基因互作网络HELP-M(intelligence genes with higher expression levels in prenatal males)、青春期女性高表达的智力基因互作网络HELP-F(intelligence genes with higher expression levels in pubertal females)。结果表明,这两个网络的关键基因均是Ep300和Ctnnb1。其中Ep300在HELP-M和HELP-F中调控了53个基因的转录,Ctnnb1在HELP-M和HELP-F中调控了45个基因转录,Ctnnb1在HELP-M以及Ep300在HELP-F中分别发挥更重要的作用。对不同发育时间的大鼠进行测序验证,发现在青春期雌性大鼠前额叶皮层中HELP-F的智力基因和关键基因Ep300、Ctnnb1表达水平显著高于雄性大鼠,并且参与了神经发育等相关生物过程。以上结果揭示了在神经发育过程中表达水平具有性别差异的智力基因网络及其关键基因。
基金funded by the National Natural Science Foundation of China(32070576,31801040,and 32270667)Lantai Young Scholars Program of Chinese History Institute(2022LTQN602)+11 种基金the National Social Science Fund of China(19VJX074 and 21CKG022)Priority Research Program of the Chinese Academy of Sciences:Pan-Third Pole Environment Study for a Green Silk Road(Pan-TPE)(XDA2004010101)the National Key Research and Development Program(2023YFC3303701-02)the Natural Science Foundation of Fujian Province of China(2023J06013)the Science and Technology Commission of Shanghai Municipality(18490750300)the National Key Research and Development Program(2020YFE0201600)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)the Major Project of National Social Science Foundation of China granted to C.C.W.(21&ZD285),S.W.(20&ZD212),and D.L.(21&ZD237)Major Special Project of Philosophy and Social Sciences Research of the Ministry of Education(2022JZDZ023)Open Research Fund of State Key Laboratory of Genetic Engineering at Fudan University(SKLGE-2310)Open Research Fund of Forensic Genetics Key Laboratory of the Ministry of Public Security(2023FGKFKT07)European Research Council(ERC)grant(ERC-2019-ADG-883700-TRAM).
文摘China's Northern and Southern Dynasties period(3rd–6th centuries AD)marked a significant era of ethnic integration in northern China.However,previous ancient DNA studies have primarily focused on northern ethnic groups,with limited research on the genetic formation of the hereditary elite family,especially considering their abundant archaeological record and clear material identity.In this study,we obtain the ancient genome of a hereditary elite family,Gao Bin(高宾,503 AD–572 AD),at 0.6473-fold coverage with 475,132 single-nucleotide polymorphisms(SNPs)on the 1240k panel.His mitochondrial haplogroup belongs to Z4 and Y-haplogroup to O1a1a2b-F2444∗.The genetic profile of Gao Bin is most similar to that of the northern Han Chinese.He can be modeled as deriving all his ancestry from Late Neolithic to Iron Age Yellow River farmers without influence from Northeast Asia,Korea,or the Mongolian Plateau.Our study sheds light on the genetic formation of hereditary elite families in the context of the Southern and Northern Dynasties ethnic integration.
文摘乳腺癌作为全球女性发病率最高的恶性肿瘤,其预后存在显著异质性。基于癌症基因组图谱(the cancer genome atlas,TCGA)数据库,对乳腺癌患者的转录组数据进行差异分析和相关性分析,筛选出尼古丁代谢相关的差异表达基因。采用单因素Cox回归分析和Lasso-Cox回归分析方法构建预后模型,并通过Kaplan-Meier生存曲线、ROC曲线、校准曲线及包含临床因素的列线图进行评估。使用基因表达总库(gene expressi on omnibus,GEO)中的GSE42568数据集作为外部验证集进行模型验证,并进一步开展免疫浸润分析和药物敏感性分析。结果发现,模型由10个尼古丁代谢相关基因组成,可作为乳腺癌的独立预后因素,并且高低风险组在免疫细胞浸润及药物敏感性上具有显著差异。构建的风险预后模型能够独立预测乳腺癌的预后情况,可为乳腺癌预后评估和个体化治疗提供新的分子标志物和潜在治疗靶点。
基金funded by the Shandong Province Humanities and Social Sciences Project“Sorting and Research on Human Bones of Han Dynasty Excavated from the Medical Center Cemetery in Linzi”granted to Zhigang Wu(2022-JCLS-12)the National Key Research and Development Program(2023YFC3303701-02)+5 种基金the National Natural Science Foundation of China(32270667)the Natural Science Foundation of Fujian Province of China(2023J06013)the Major Project of the National Social Science Foundation of China granted to Chuan-Chao Wang(21&ZD285)Open Research Fund of State Key Laboratory of Genetic Engineering at Fudan University(No.SKLGE-2310)Open Research Fund of Forensic Genetics Key Laboratory of the Ministry of Public Security(2023FGKFKT07)Major Special Project of Philosophy and Social Sciences Research of the Ministry of Education(2022JZDZ023).
文摘Shandong province,located in the Lower Yellow River,is one of the birthplaces of ancient Chinese civilization.However,the comprehensive genetic histories of this region have remained largely unknown until now due to a lack of ancient human genomes.Here,we present 21 ancient genomes from Shandong dating from the Warring States period to the Northern Dynasties.Unlike the early Neolithic samples from Shandong,the historical samples are most closely related to post-Late Neolithic populations of the Middle Yellow River Basin,suggesting a population turnover in Shandong from the Neolithic Age to the Historical era.In addition,we detect a close genetic affinity between the historical samples in Shandong and present-day Han Chinese,showing long-term genetic stability in Han Chinese,at least since the Warring States period.
基金supported by the National Natural Science Foundation of China(42372017 and 42072018)the Fundamental Research Funds for the Central Universities(2022CXTD24)。
文摘The Hehuang Valley,situated in the northeastern section of the Qinghai-Tibet Plateau,represents the upper reaches of the Yellow River(Fig.1A).It is a significant geographic region of origin for numerous Neolithic cultures,including the Majiayao,Zongri,and Qijia cultures(Dong et al.,2013).
基金supported by the National Natural Science Foundation of China(41925009)National Key R&D Program of China(2022YFE0203800)+2 种基金the Ministry of Finance of the People’s Republic of China(YSBR-019)Science and Technology Innovation Team of Shaanxi Province(2024RS-CXTD-74)Xiaohong Wu was supported by the Key National Social Science Foundation of China(No.16ZDA144).
文摘Yunnan in southwest China is a geographically and ethnically complex region at the intersection of southern China and Southeast Asia,and a focal point for human migrations.To clarify its maternal genetic history,we generated 152 complete mitogenomes from 17 Yunnan archaeological sites.Our results reveal distinct genetic histories segregated by geographical regions.Maternal lineages of ancient populations from northwestern and northern Yunnan exhibit closer affinities with past and present-day populations from northern East Asia and Xizang,providing important genetic evidence for the migration and interaction of populations along the Tibetan-Yi corridor since the Neolithic.Between 5500 and 1800 years ago,central Yunnan populations maintained their internal genetic relationships,including a 7000-year-old basal lineage of the rare and widely dispersed haplogroup M61.At the Xingyi site,changes in mitochondrial DNA haplogroups occurred between the Late Neolithic and Bronze Age,with haplogroups shifting from those predominant in the Yellow River region to those predominant in coastal southern China.These results highlight the high diversity of Yunnan populations during the Neolithic to Bronze Age.
基金funded by the following grants and contracts:Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38020400 to S.W.)the National Natural Science Foundation of China(32325013 to S.W.,32271186 to J.T.,31900408 to M.Z.)+5 种基金the CAS Project for Young Scientists in Basic Research(YSBR-077 to S.W.)Shanghai Science and Technology Commission Excellent Academic Leaders Program(22XD1424700 to S.W.)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-066 to L.J.and J.W.)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01 to L.J.and S.W.)the National Science and Technology Basic Research Project(2015FY111700 to L.J.)the 111 Project(B13016 to L.J.).
文摘Facial morphology,a complex trait influenced by genetics,holds great significance in evolutionary research.However,due to limited fossil evidence,the facial characteristics of Neanderthals and Denisovans have remained largely unknown.In this study,we conduct a large-scale multi-ethnic meta-analysis of the genome-wide association study(GWAS),including 9674 East Asians and 10,115 Europeans,quantitatively assessing 78 facial traits using 3D facial images.We identify 71 genomic loci associated with facial features,including 21 novel loci.We develop a facial polygenic score(FPS)that enables the prediction of facial features based on genetic information.Interestingly,the distribution of FPSs among populations from diverse continental groups exhibits relevant correlations with observed facial features.Furthermore,we apply the FPS to predict the facial traits of seven Neanderthals and one Denisovan using ancient DNA and align predictions with the fossil records.Our results suggest that Neanderthals and Denisovans likely share similar facial features,such as a wider but shorter nose and a wider endocanthion distance.The decreased mouth width is characterized specifically in Denisovans.The integration of genomic data and facial trait analysis provides valuable insights into the evolutionary history and adaptive changes in human facial morphology.
基金the financial support received from the National Natural Science Foundation of China(82202078)the National Social Science Foundation of China(23&ZD203)+4 种基金support for G.H.includes National Natural Science Foundation of China(82402203)the Open Project of the Key Laboratory of Forensic Genetics of the Ministry of Public Security(2022FGKFKT05)the Center for Archaeological Science of Sichuan University(23SASA01)the 1‧3‧5 Project for Disciplines of Excellence at West China Hospital,Sichuan University(ZYJC20002)the Sichuan Science and Technology Program(2024NSFSC1518).
文摘The reconstruction of demographic history using ancient and modern genomic resources reveals extensive interactions and admixture between ancient nomadic pastoralists and the social organizations of the Chinese Central Plain.However,the extent to which Y-chromosome genetic legacies from nomadic emperor-related ancestral lineages influence the Chinese paternal gene pool remains unclear.Here,we genotype 2717 ethnolinguistically diverse samples belonging to C2a lineages,perform whole-genome sequencing on 997 representative samples,and integrate these data with ancient genomic sequences.We reconstruct the evolutionary histories of Northern Zhou-,Qing emperor-,and pastoralist-related lineages to assess their genetic impact on modern Chinese populations.This reassembled fine-scale Ychromosome phylogeny identifies deep divergence and five Neolithic expansion events contributing differently to the formation of northern Chinese populations.Phylogeographic modeling indicates that the nomadic empires of the Northern Zhou and Qing dynasties genetically originated from the Mongolian Plateau.Phylogenetic topology and shared haplotype patterns show that three upstream ancestors of Northern Zhou(C2a1a1b1a2a1b-FGC28857),Donghu tribe(C2a1a1b1-F1756),and Qing(C2a1a3a2-F10283)emperor-related lineages expanded during the middle Neolithic,contributing significantly to genetic flow between ancient northeastern Asians and modern East Asians.Notably,this study reveals limited direct contributions of Emperor Wu of Northern Zhou’s lineages to modern East Asians.
