- 石宏(Hong Shi)教授，硕士生导师
Ph.D., Professor, Doctoral supervisor,
Young and middle-aged academic and technological leader of Yunnan.
Email:shih@lpbr.cn
一、受教育及工作经历 EDUCATION AND WORK EXPERIENCE
2002.9-2006.7 博士研究生（获理学博士学位），导师：宿兵研究员
中国科学院昆明动物研究所遗传资源与进化国家重点实验室，
中国科学院昆明灵长类研究中心。1999.9-2002.7 硕士研究生（获理学硕士学位），导师：肖春杰教授云南大学人类遗传学研究中心1992.9-1996.7本科（获农学学士学位）西南农业大学（西南大学）Ph.D. in Human Population Genetics (Chinese Academy of Sciences) 2006 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology and Kunming Primate Research Centre, CAS
Supervisor: Professor Bing Su (Comparative genomic Group)
M.Sc. in Genetics (Yunnan University) 2002 Human Genetics Centre, Yunnan University
Supervisor: Professor Chun-jie Xiao
B.Sc. in Aquaculture (Southwest Agriculture University) 1996
Fishery department, Southwest Agriculture University (Southwest University)
Professor (2015--present)
Principal investigator, primate genetic diversity and personalized medicine.
Institute of primate translational medicine, Kunming University of Science and Technology.
Associate Professor (2009-2014)
State Key Laboratory of Genetic Resources and Evolution,
Kunming Institute of Zoology and Kunming Primate Research Centre, CAS
Assistant Research Fellow (2006-2009)
State Key Laboratory of Genetic Resources and Evolution,
Kunming Institute of Zoology and Kunming Primate Research Centre, CAS
二、研究工作经历
2015.1-至今，教授。昆明理工大学灵长类转化医学研究中心。灵长类的基因组多样性与临床前个体化医疗研究方向负责人。2009.9—2014.12，副研究员。中国科学院大学硕士导师。中国科学院昆明动物研究所遗传资源与进化国家重点实验室。2006.8-2009.8，助理研究员。中国科学院昆明动物研究所遗传资源与进化国家重点实验室。三、研究经历
人类群体遗传学长期从事人类群体遗传学和分子进化研究，从遗传学角度探讨东亚现代人的起源和史前迁徙问题，以及特殊人群的遗传学源流和形成历史。以Y染色体、线粒体及常染色体遗传标记展开研究工作。环境压力下东亚人群的适应性进化目前开展的研究工作有：人群p53调控通路对环境压力的研究；高原低氧环境对人群的适应选择；东亚人群肤色适应性进化的遗传学机制；东亚现代人对疟疾的适应性进化；以及西南亚热带区域人群特有疾病的遗传易感性研究等。目前开展的研究：东亚人群环境适应性进化研究从全基因组水平比较具有不同适应性特征人群之间的遗传差异信息，结合代谢通路分析基因功能信息，寻找调控现代人群中环境适应性进化的关键基因。并通过对候选基因的变异位点在人群间的分型验证来构建基因的分子进化模式，评估自然选择对基因进化的影响。利用遗传相关性分析寻找与环境适应表型相关的关键序列变异，进一步开展候选基因的功能分析，揭示基因变异导人群环境适应的分子进化机制，并在细胞水平和动物模型上探讨其分子机理及其功能后果。目前主要集中在分析东亚人群肤色适应性及探讨东亚人群抗疟疾适应性进化的分子机制，阐明东亚人群如何通过遗传变异，并在生理机能上进化出适应性表型。该方向的目标是系统探讨东亚人特殊表型和生理特征形成的遗传基础，以及探讨了环境选择和生活方式改变对东亚人群遗传结构的影响。中国西南人群队列及精准医学中国西南地区拥有众多的少数民族人群，人群分布的自然环境复杂多变，是研究人类遗传多样性和地区人群的特色疾病的理想之地。人群经过长期适应性进化形成了许多遗传变异特征，分析人群适应的分子机制，能帮助理解人类群体的进化历史、群体对疾病的易感性、群体对药物的敏感性以及遗传变异与环境因素间的相互作用等。随着精准医疗的开展，西南地区自然人群队列研究是一个不可缺少的部分。中国西南地区具有地中海贫血，葡萄糖-6-磷酸脱氢酶缺乏症、先天性心脏病及肺动脉高压等地区特殊疾病，通过建立西南地区人群的大健康数据库，为该地区人群疾病的临床个性化治疗及防控提供基础数据。该研究将探讨西南地区人群疾病表型与遗传变异之间的关系，为疾病治疗和预防提供遗传学数据支持。灵长类基因多样性与个性化医疗研究在全基因组水平比较人类和非人灵长类的遗传相似性、差异性及其生物学效应；研究非人灵长类在群体水平的遗传多态性及其表型的关系，为疾病动物模型和个性化医疗的临床前研究提供基础数据。利用非人灵长类基因组中丰富的序列多态性可以在临床前分析药物靶点和药物代谢基因的序列差异对疗效和药物副作用产生的影响，从而为临床的个体化医疗提供重要的信息。RESEARCH EXPERIENCEHuman population genetics
The origin and prehistoric migration of the modern humans in East Asia is an interesting question. Research was performed by Y chromosome, mtDNA and autosomal markers.
Adaptation evolution of the East Asians under the environmental stresses
East Asians are the most widely dispersed populations. They distributed from the tropic regions to the polar regions (from Indonesia to Siberia) and from low altitude coastal lands to the Tibet Plateau (3,500-5,000 meters high). East Asian populations dispersed in the continent and met different environmental stress changes during the recent tens of thousands of years.
There had the huge changes in East Asian populations, such as adaptation evolution of p53 pathway under environmental stresses; adaptation evolution of hypoxia in Tibetan populations; adaptation evolution of the skin color in East Asians; natural selection of malaria in East Asians; the genetic susceptibility of tropical and subtropical zone diseases in the southwestern populations of China.
RESEARCH INTERESTING
Adaptation evolution of the East Asians
My research in this part is aimed to answer the questions about what kinds of genetic changes resulted in the adaptation evolution of East Asians to meet different environmental stresses.
The genetic differences among populations with different adaptive characteristics are detected at genome level. Combining analysis with function pathways, the functional mutations of genes are searched, and the key mutations that regulate the evolution of environmental adaptation in modern populations are found. The molecular evolution model of the candidate gene is constructed among populations, and the effect of natural selection on gene evolution is evaluated. Based the genetic correlation analysis to find key mutations related to environmental adaptation phenotype, further functional analysis of candidate genes is carried out to reveal the molecular evolutionary mechanism of environmental adaptation, and to explore its molecular mechanism and functional consequences at cellular level and animal model.
At present, studies focus on the analysis of skin color adaptability and the molecular mechanism of adaptive evolution of anti-malaria in East Asian populations. To systematically answer how adaptive phenotype evolved through genetic variation and physiological function change, and to explore the effects of environmental selection and lifestyle changes on the genetic structure of East Asian populations.
Population cohort and precision medicine in southwestern China
There have a large number of ethnic groups in Southwest China and the natural environment is complex and changeable. Through long-term adaptive evolution, populations have formed many genetic variation characteristics. It is an ideal place to study human genetic diversity and characteristic diseases of regional populations.
The molecular mechanism of adaptation can help understand the evolution history of human population, the susceptibility of population to diseases, the sensitivity of population to drugs, and the interaction between genetic variation and environmental factors.
The cohort study of natural populations is important to development of precision medicine. Southwest China has special diseases such as thalassemia, glucose-6-phosphate dehydrogenase deficiency, congenital heart disease and pulmonary hypertension. This study will explore the relationship between disease phenotypes and genetic variations in the populations of Southwest China, and provide genetic data support for disease treatment and prevention.
Primate genetic diversity and personalized medicine
The genetic similarities, differences and biological effects between human with non-human primates at the genome-wide level are compared, and analyze the relationship between genetic polymorphism and phenotype of non-human primates at the population level. It will provide basic data for animal models of diseases and pre-clinical research of personalized medicine. The abundant genetic polymorphisms in non-human primate genomes can be used to analyze the effects of mutations on drug metabolism in pre-clinical practice.
四、主持和参与基金 FUNDS AWARD
国家自然科学基金重大研究计划集成项目，91631307，亚欧人群色素相关表型的进化与多基因作用机制，2017/01-2019/12、288万元（本人72万元）、在研、主要参与人。国家自然科学基金面上项目，31371268、东亚人群抗疟疾感染的遗传适应性进化研究、2014/01-2017/12、100万元、在研、主持。超级973子课题，2012CBA01303、异种、异源细胞和器官的灵长类动物移植探索及其免疫学基础、2012/10-2015/10、100万元、已结题、学术骨干。国家自然科学基金重大研究计划培育项目，91131001、东亚人群肤色适应性进化的遗传 机制研究、2012/01-2014/12、100万元、已结题、主持。国家自然科学基金面上项目，31071101、环境压力对人类MDMX基因的进化选择的研究、2011/01—2013/12、38万元、已结题、主持。云南省中青年学术带头人后备人才培养计划，2010CI044、人类遗传学、2010/08—2015/08、12万元、已结题、主持。云南省自然科学基金面上项目，2009CD107、环境压力对人类p53基因家族进化选择作用的研究、2009/12—2012/12、7.5万元、已结题、主持。国家自然科学基金青年基金，30700445、Y染色体单倍型组D与东亚现代人的起源和迁移历史、2008/01—2010/12、17万元、已结题、主持。中国科学院西部博士项目，环境压力诱导p53抑癌调控通路遗传变异在东亚人群中的研究、2008/01—2010/12、20万元、结题评估为优秀、主持。973子课题，2007CB815705、基因和基因家族/群功能的选择和进化、2007/07—2012/08、500万元（本人为135万元）、已结题、学术骨干。1. Integration Project of Natural Science Foundation of China (NSFC) (91631303)￥10,000,000.00
My position: Project Backbone
2018-2019(Project title: The impact of admixture on genome diversity in East Asian and South Asian populations)
2. Integration Project of Natural Science Foundation of China (NSFC) (91631307)￥2,880,000.00
My position: Project Backbone
2017-2019(Project title: The evolution and genetic mechanisms of pigmentation related phenotypes in East Asian and European populations)
3. General grant of National Science Foundation of China (NSFC) (31371268)￥1,000,000.00
My position: Principal Investigator
2014-2017(Project title: Genetic adaptation of anti-Malaria in East Asian populations)
4. Key project of National Science Foundation of China (NSFC) (91131001)￥1,000,000.00
My position: Principal Investigator
2012-2014(Project title: The genetic variations of adaptation evolution in East Asians)
5. General grant of National Science Foundation of China (NSFC) (31071101)￥380,000.00
My position: Principal Investigator
2011-2013(Project title: The human evolution of MDMX under the environmental stress)
6. General grant of National Science Foundation of China (NSFC) (30700445)￥170,000.00
My position: Principal Investigator
2008-2010(Project title: The Y chromosome haplogroup D and the origin of East Asian)
7. Grant for doctors of west districts, CAS foundation ￥200,000.00
My position: Principal Investigator
2008-2010(Project title: The adaptation evolution of the p53 pathway under the Environmental Stresses)
奖励情况 HONORS
- 获2015年度云南省中青年学术带头人。
- 获2013年度云南省自然科学一等奖（排名第二）。
- 获2012年度云南省自然科学一等奖（排名第四）。
- 获2012年度中国科学院王宽诚基金会“西部学者突出贡献奖”。
- 获2011年“第八届青藏高原青年科技奖”。
Young and middle-aged academic and technological leader of Yunnan (2015)
The first prize Natural Science in Yunnan Province of 2013 (2nd in name list)
The first prize Natural Science in Yunnan Province of 2012 (4th in name list)
“Outstanding Contribution Award for Western Scholars” of 2012, Wang Kuancheng Foundation, Chinese Academy of Sciences
The 8th Qinghai-Tibet Plateau Youth Science and Technology Award of 2011
五、代表性论文 PUBLICATIONS
1. Yang ZH, Shi H(co-first author), Ma PC, Zhao SL, Kong QH, Bian TH, Gong C, Zhao Q, Liu Y, Qi XB, Zhang XM, Han YL, Liu JW, Li QW, Chen H, Su B. Darwinian Positive Selection on the Pleiotropic Effects of KITLG Explain Skin Pigmentation and Winter Temperature Adaptation in Eurasians. Mol Biol Evol. 2018, 35(9):2272-2283. (DOI: 10.1093/molbev/ msy136) (IF:10.217)
2. Bhandari S, Zhang XM, Cui CY, Yangla, Liu L, Ouzhuluobu, Baimakangzhuo, Gonggalanzi , Bai CJ, Bianba, Peng Y, Zhang H, Xiang K, Shi H, Liu SM, Gengdeng, Wu TY, Qi XB, Su B. Sherpas share genetic variations with Tibetans for high-altitude adaptation. Mol Genet & Genom Med. 2017 JAN 5 (1): 76-84. (DOI: 10.1002/mgg3.264)
3.Yang ZH, Zhong H, Chen J, Zhang XM, Zhang H, Luo X, Xu SH, Chen H, Lu DS, HanYL, Li JK, Fu LJ, Qi XB, Peng Y, Xiang K, Lin Q, Guo Y, Li M, Cao XY, Zhang YF, Liao SY, Peng YM, Zhang L, Guo XS, Dong SS, Liang F, Wang J, Willden A, Seang Aun H, Serey B, Sovannary T, Bunnath L, Samnom H, Mardon G, Li QW, Meng AM *, Shi H * （co-correspondent author）& Su B *. A genetic mechanism for convergent skin lightening during recent human evolution. Mol Bio Evol. 2016 May 33(5):1177–1187.(IF:13.649)
4. Zhang XM, Liao SY, Qi XB, Liu JW, Kampuansai J, Zhang H, Yang ZH, Serey B, Sovannary T, Bunnath L, Seang Aun H, Samnom H, Kangwanpong D, Shi H*（co-correspondent author） & Su B. Y-chromosome diversity suggests southern origin and Paleolithic backwave migration of Austro-Asiatic speakers from eastern Asia to the Indian subcontinent. Sci. Rep. 2015 Oct, 5: 15486; doi: 10.1038/srep15486.
5. Zhang XM, Kampuansai J, Qi XB, Yan S, Yang ZH, Serey B, Sovannary T, Bunnath L, Seang Aun H, Samnom, Kutanan W, Luo X, Liao SY, Kangwanpong D, Jin L, Shi H*（co-correspondent author）and Su B*.An Updated Phylogeny of the Human Y-Chromosome Lineage O2a-M95 with Novel SNPs. PLoS ONE. 2014 June, 9(6)：e101020.
6. Kraaijenbrink T, van der Gaag KJ, Zuniga SB, Xue Y, Carvalho-Silva DR, Tyler-Smith C, Jobling M A, Parkin EJ, Su B, Shi H, Xiao CJ, Tang WR, Kashyap VK, Trivedi R, Sitalaximi T, Banerjee J, Tshering of Gaselô K, Tuladhar NM, Opgenort JRML, van Driem GL, Barbujani G, Peter de Knijff. A Linguistically Informed Autosomal STR Survey of Human Populations Residing in the Greater Himalayan Region. PLoS ONE. 2014 March 9(3): e91534.
7. Li M, Luo XJ, Rietschel M, Lewis CM, Mattheisen M, Müller-Myhsok B, Jamain S, Leboyer M, Landén M, Thompson PM, Cichon S, Nöthen MM, Schulze TG, Sullivan PF, Bergen SE, Donohoe G, Morris DW, Hargreaves A, Gill M, Corvin A, Hultman C, Toga AW, Shi L, Lin Q, Shi H, Gan L, Meyer-Lindenberg A, Czamara D, Henry C, Etain B, Bis JC, Ikram MA, Fornage M, Debette S, Launer LJ, Seshadri S, Erk S, Walter H, Heinz A, Bellivier F, Stein JL, Medland SE, Arias Vasquez A, Hibar DP, Franke B, Martin NG, Wright MJ; MooDS Bipolar Consortium; Swedish Bipolar Study Group; Alzheimer’s Disease Neuroimaging Initiative; ENIGMA Consortium; CHARGE Consortium, Su B. Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility. Mol Psychiatry. 2014 Apr;19(4):452-61. （IF 15.147）
8. Zhang XM, Qi XB, Yang ZH, Serey B, Sovannary T, Bunnath L, Seang Aun H, Samnom, Zhang H, Lin Q, van Oven M, Shi H *（co-correspondent author） and Su B. Analysis of Mitochondrial Genome Diversity Identifies Novel and Ancient Maternal Lineages in Cambodian Aborigines. Nature Communications. 2013, 4:2599.（IF 10.742）
9. Qi XB, Cui CY, Peng Y, Zhang XM, Yang ZH, Zhong H, Zhang H, Xiang K, Cao XY, Wang Y, Ouzhuluobu, Basang, Ciwangsangbu, Bianba, Gonggalanzi, Wu TY, Chen H, Shi H*（co-correspondent author）and Su B. Genetic evidence of Paleolithic colonization and Neolithic expansion of modern humans on the Tibetan Plateau. Mol Biol Evol. 2013, 30(8):1761-1778. （IF 14.308）
10. Shi H (co-correspondent author), Qi XB, Zhong H, Peng Y, Zhang XM, Ma RLZ and Su B. Genetic evidence of an East Asian origin and Paleolithic northward migration of Y-chromosome haplogroup N. PLoS ONE. 2013 June，8(6)：e66102.
11. Xiang K, Ouzhuluobu, Peng Y, Yang ZH, Zhang XM, Cui CY, Zhang H, Li M, Zhang YF, Bianba, Gonggalanzi, Basang, Ciwangsangbu, Wu TY, Chen H, Shi H, Qi XB, Su B. Identification of a Tibetan-specific mutation in the hypoxic gene EGLN1 and its contribution to high-altitude adaptation. Mol Biol Evol. 2013, 30(8):1889-1898. （IF 14.308）
12. Li M, Luo XJ, Xiao X, Shi L, Liu XY, Yin LD, Ma XY, Yang SY, Pu XF, Yu J, Diao HB, Shi H, and Su B. Analysis of common genetic variants identifies RELN as a risk gene for schizophrenia in Chinese population. The World Journal of Biological Psychiatry, 2011 March, 14(2): 91-99.
13. Li R, Zhang XM, Campana MG, Huang JP, Chang ZH, Qi XB, Shi H, Su B, Zhang RF, Lan XY, Chen H and Lei CZ. Paternal origins of Chinese cattle. Animal Genetics. 2013, 44(4):446-449.
14. Qi XB, Shi H, Cui CY, Bianba, Ouzhuluobu, Wu TY and Su B. Peopleing of the Tibetan Plateau and genetic adaptation to high-altitude hypoxia in Tibetans. Science. 2012 December; 388(6113):1485(12-13).
15. Shi H. A commentary on “A multiplex SNP assay for the dissection of human Y-chromosome haplogroup O representing the major paternal lineage in East and Southeast Asia”. J Hum Genet. 2012, 57:5.
16. Peng Y, Yang ZH, Zhang H, Cui CY, Qi XB, Luo XJ, Tao X, Wu TY, Ouzhuluobu, Basang, Ciwangsangbu, Danzengduojie, Chen H, Shi H*（co-correspondent author）& Su B*. Genetic Variations in Tibetan Populations and High-Altitude Adaptation at the Himalayas. Mol Biol Evol. 2011, 28:1075-1081. （IF 11.221）
17. Zhong H, Shi H,*（co-first author）, Qi XB, Duan ZY, Tan PP, Jin L, Su B & Ma RZ. Extended Y-chromosome investigation suggests post-Glacial migrations of modern humans into East Asia via the northern route. Mol Biol Evol. 2011, 28, 717-727.（IF 11.221）
18. Shi H and Su B. Molecular Adaptation of Modern Human Populations. Intern J Evol Bio. 2011, 484769, doi:10.4061/2011/484769.
19. Peng Y, Shi H, Qi XB, Xiao CJ, Zhong H, Ma Z RL, Su B. Genetic evidence of rice culture driven selection on the ADH1B Arg47His polymorphism in East Asian populations. BMC Evolu Biol. 2010, 10:15.
20. Zhong H, Shi H, Xiao CJ, Ma RLZ and Su B. Global Distribution of Y-Chromosome Haplogroup C Reveals the Prehistoric Migration Routes of African Exodus and Early Settlement in East Asia. J Hum Genet. 2010, 55, 428-35.
21. Shou WH, Qiao EF, Wei CY, Dong YL, Tan SJ, Shi H, Tang WR, Xiao CJ. Y-chromosome distributions among populations in Northwest China identify significant contribution from Central Asian pastoralists and lesser influence of western Eurasians. J Hum Genet. 2010, 5:1–9.
22. Shi H, Tan SJ, Zhong H, Hu WW, Levine A, Xiao CJ, Peng Y, Qi XB, Shou WH, Ma Z RL, Li Y, Su B and Lu X. Winter Temperature and UV Are Tightly Linked to Genetic Changes in the p53 Tumor Suppressor Pathway in Eastern Asia. Am J Hum Genet. 2009 April; 84(4), 534–541. (Featured Article)（IF 12.16）
23. Shi H and Su B. Origin of Modern Humans in East Asia: clues from the Y chromosome. Front Biol China. 2009, 4(3): 241–247.
24. Shi H, Zhong H, Peng Y, Dong YL, Qi XB, Zhang F, Liu LF, Tan SJ, Ma RL, Xiao CJ, Wells S, Jin L and Su B. Y chromosome evidence of earliest modern human settlement in East Asia and multiple origins of Tibetan and Japanese populations. BMC Biology. 2008 October, 6:45.
25. Kraaijenbrink T, Zuniga S, Su B, Shi H, Xiao CJ, Tang WR, Knijff de P. Allele frequency distribution of 21 forensic autosomal STRs in 7 populations from Yunnan, China. Forensic Science International: Genetics, 2008(3): e11–e12.
26. Shi H, Dong YL, Wen B, Xiao CJ, Underhill PA, Shen PD, Chakraborty R, Jin L and Su B. Y-chromosome evidence of southern origin of the East Asian-specific haplogroup O3-M122. Am J Hum Genet. 2005 Sep; 77(3):408-19. (IF 12.65)
27. Shi H, Dong YL, Li WX, Yang J, Li KY, Zan RG & Xiao CJ. The geographic polymorphisms of Y chromosome at YAP locus among 25 ethnic groups in Yunnan, China. Sci China C Life Sci. 2003 April; 46 (2):135-140.
28. Chen XH, Shi H, Liu XL and Su B. The testis-specific apoptosis related gene TTL.6 underwent adaptive evolution in the lineage leading to humans. Gene, 2006 Mar 29; 370C:58-63.
29. Wang YQ, Qian YP, Yang S, Shi H, Liao CH, Zheng HK, Wang J, Lin AA, Cavalli-Sforza LL, Underhill PA, Chakraborty R, Jin L and Su B. Accelerated evolution of the pituitary adenylate cyclase-activating polypeptide precursor gene during human origin. Genetics. 2005 Jun; 170 (2):801-6.
30. Wen B, Shi H, Ren L, Xue HF, Li KY, Zhang WY, Su B, Shi SH, Jin L and Xiao CJ. The origin of Mosuo people as revealed by mtDNA and Y chromosome variation. Sci China C Life Sci. 2004 Feb; 47 (1):1-10.
31. Wen B, Xie X, Gao S, Li H, Shi H, Song X, Qian T, Xiao C, Jin J, Su B, Lu D, Chakraborty R and Jin L. Analyses of genetic structure of Tibeto-Burman populations reveals sex-biased admixture in southern Tibeto-Burmans. Am J Hum Genet. 2004 May; 74 (5):856-65. (IF 12.34)
32. Yang X, Yang Z, Shi H, Dong Y, Yang J, Zeng W, Gao L and Xiao C. Y-STR polymorphisms among five Chinese minorities, Mosuo, Mongolian, Naxi, Pumi and Tibetan, in Yunnan Province, PR China. Ann Hum Biol. 2004 Jan-Feb; 31 (1):103-11.
33. Qi XB, Yang S, Zheng HK, Wang YQ, Liao CH, Liu Y, Chen XH, Shi H, Yu XJ, Lin AA, Cavalli-Sforza LL, Wang J and Su B (2007) Detecting positive Darwinian selection in brain-expressed genes during human evolution. Chinese Science Bulletin 52:324-335.
