1、分 子 生 物 学,南京农业大学生命科学学院 沈文飙,绪论,分子生物学的概念 分子生物学的研究内容 分子生物学与生物化学之间的关系 分子生物学的发展历程 21世纪分子生物学发展的趋势,分子生物学的概念,分子生物学是研究核酸、蛋白质等生物大分子的结构与功能，并从分子水平上阐明蛋白质与蛋白质、蛋白质与核酸之间的互作及其基因表达调控机理的学科 广义上，分子生物学包括对蛋白质和核酸等生物大分子结构与功能的研究，以及从分子水平上阐明生命现象和生物规律，但目前主要研究基因的结构与功能、复制、转录、表达和调控，确切地应称为分子遗传学,DNA-遗传密码的携带者,引自Neil Campbell著Biology第
2、4版,1996,胰岛素,蛋白酶,蜘蛛毒素,光合作用受体,金属硫蛋白,分子生物学的研究内容,基因与基因组的结构与功能 DNA的复制、转录和翻译 基因表达调控的研究 DNA重组技术 结构分子生物学,分子生物学与生物化学之间的关系,分子生物学与生物化学之间的关系密不可分分子生物学从分子水平研究生命现象，生物化学研究从分子水平研究生命现象的本质两者你中有我，我中有你,分子生物学的发展历程,19441966年，人类对DNA和遗传信息传递的认识阶段 19671978年，重组DNA技术的建立和发展阶段 1979年至今，重组DNA技术的应用和分子生物学迅速发展阶段,分子生物学的发展历程,1944年，Avery
3、 证明DNA是遗传物质 1950年，Chargaff 提出Chargaff定则 1953年，Watson & Crick 成功解析了DNA分子二级结构 1961年，Jacob & Monod 提出了调节基因表达的操纵子模型,Nature 171, 737-734 (1953) (C) Macmillan Publishers Ltd. Molecular structure of Nucleic Acids WATSON, J. D. & CRICK, F. H. C. Medical Research Council Unit for the Study of Molecular Struc
4、ture of Biological Systems, Cavendish Laboratory, Cambridge.,A Structure for Deoxyribose Nucleic Acid We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest.,Figure 1 This figure is purely diag
5、rammatic. The two ribbons symbolize the two phophate-sugar chains, and the horizonal rods the pairs of bases holding the chains together. The vertical line marks the fibre axis.,分子生物学的发展历程,1970年，Smith & Wilcox 分离到第一种限制性核酸内切酶 19721973年，Boyer & Berg 发展了重组DNA技术，并完成了第一个细菌基因的克隆，开创基因工程的新纪元 1975年，Southern
6、发明了DNA片段的印迹法,分子生物学的发展历程,1981年，Cech 发现了ribozyme 1982年，Prusiner 发现了朊病毒prion 1985年，Karry Mullis 发明了PCR反应 1988年，人类基因组计划启动 1998年，克隆羊多利诞生，同年GenBank 公布了最新的人类基因图谱,Initial sequencing and analysis of the human genome Nature 409, 860 - 921 (2001), 15 February 2001 International Human Genome Sequencing Consorti
7、um Whitehead Institute for Biomedical Research, Center for Genome Research: ERIC S. LANDER1*, LAUREN M. LINTON1, BRUCE BIRREN1*, CHAD NUSBAUM1*, MICHAEL C. ZODY1*, JENNIFER BALDWIN1, KERI DEVON1, KEN DEWAR1, MICHAEL DOYLE1, WILLIAM FITZHUGH1*, ROEL FUNKE1, DIANE GAGE1, KATRINA HARRIS1, ANDREW HEAFOR
8、D1, JOHN HOWLAND1, LISA KANN1, JESSICA LEHOCZKY1, ROSIE LEVINE1, PAUL MCEWAN1, KEVIN MCKERNAN1, JAMES MELDRIM1, JILL P. MESIROV1, CHER MIRANDA1, WILLIAM MORRIS1, JEROME NAYLOR1, CHRISTINA RAYMOND1, MARK ROSETTI1, RALPH SANTOS1, ANDREW SHERIDAN1, CARRIE SOUGNEZ1, NICOLE STANGE-THOMANN1, NIKOLA STOJAN
9、OVIC1, ARAVIND SUBRAMANIAN1 & DUDLEY WYMAN1 The Sanger Centre: JANE ROGERS2, JOHN SULSTON2*, RACHAEL AINSCOUGH2, STEPHAN BECK2, DAVID BENTLEY2, JOHN BURTON2, CHRISTOPHER CLEE2, NIGEL CARTER2, ALAN COULSON2, REBECCA DEADMAN2, PANOS DELOUKAS2, ANDREW DUNHAM2, IAN DUNHAM2, RICHARD DURBIN2*, LISA FRENCH
10、2, DARREN GRAFHAM2, SIMON GREGORY2, TIM HUBBARD2*, SEAN HUMPHRAY2, ADRIENNE HUNT2, MATTHEW JONES2, CHRISTINE LLOYD2, AMANDA MCMURRAY2, LUCY MATTHEWS2, SIMON MERCER2, SARAH MILNE2, JAMES C. MULLIKIN2, ANDREW MUNGALL2, ROBERT PLUMB2, MARK ROSS2, RATNA SHOWNKEEN2 & SARAH SIMS2 Washington University Gen
11、ome Sequencing Center ROBERT H. WATERSTON3*, RICHARD K. WILSON3, LADEANA W. HILLIER3, JOHN D. MCPHERSON3, MARCO A. MARRA3, ELAINE R. MARDIS3, LUCINDA A. FULTON3, ASIF T. CHINWALLA3, KYMBERLIE H. PEPIN3, WARREN R. GISH3, STEPHANIE L. CHISSOE3, MICHAEL C. WENDL3, KIM D. DELEHAUNTY3, TRACIE L. MINER3,
12、ANDREW DELEHAUNTY3, JASON B. KRAMER3, LISA L. COOK3, ROBERT S. FULTON3, DOUGLAS L. JOHNSON3, PATRICK J. MINX3 & SANDRA W. CLIFTON3 US DOE Joint Genome Institute: TREVOR HAWKINS4, ELBERT BRANSCOMB4, PAUL PREDKI4, PAUL RICHARDSON4, SARAH WENNING4, TOM SLEZAK4, NORMAN DOGGETT4, JAN-FANG CHENG4, ANNE OL
13、SEN4, SUSAN LUCAS4, CHRISTOPHER ELKIN4, EDWARD UBERBACHER4 & MARVIN FRAZIER4 Baylor College of Medicine Human Genome Sequencing Center: RICHARD A. GIBBS5*, DONNA M. MUZNY5, STEVEN E. SCHERER5, JOHN B. BOUCK5, ERICA J. SODERGREN5, KIM C. WORLEY5, CATHERINE M. RIVES5, JAMES H. GORRELL5, MICHAEL L. MET
14、ZKER5, SUSAN L. NAYLOR6, RAJU S. KUCHERLAPATI7, DAVID L. NELSON & GEORGE M. WEINSTOCK8 RIKEN Genomic Sciences Center: YOSHIYUKI SAKAKI9, ASAO FUJIYAMA9, MASAHIRA HATTORI9, TETSUSHI YADA9, ATSUSHI TOYODA9, TAKEHIKO ITOH9, CHIHARU KAWAGOE9, HIDEMI WATANABE9, YASUSHI TOTOKI9 & TODD TAYLOR9 Genoscope an
15、d CNRS UMR-8030: JEAN WEISSENBACH10, ROLAND HEILIG10, WILLIAM SAURIN10, FRANCOIS ARTIGUENAVE10, PHILIPPE BROTTIER10, THOMAS BRULS10, ERIC PELLETIER10, CATHERINE ROBERT10 & PATRICK WINCKER10 GTC Sequencing Center: DOUGLAS R. SMITH11, LYNN DOUCETTE-STAMM11, MARC RUBENFIELD11, KEITH WEINSTOCK11, HONG M
16、EI LEE11 & JOANN DUBOIS11 Department of Genome Analysis, Institute of Molecular Biotechnology: ANDR ROSENTHAL12, MATTHIAS PLATZER12, GERALD NYAKATURA12, STEFAN TAUDIEN12 & ANDREAS RUMP12 Beijing Genomics Institute/Human Genome Center: HUANMING YANG13, JUN YU13, JIAN WANG13, GUYANG HUANG14 & JUN GU15
17、 Multimegabase Sequencing Center, The Institute for Systems Biology: LEROY HOOD16, LEE ROWEN16, ANUP MADAN16 & SHIZEN QIN16 Stanford Genome Technology Center: RONALD W. DAVIS17, NANCY A. FEDERSPIEL17, A. PIA ABOLA17 & MICHAEL J. PROCTOR17 Stanford Human Genome Center: RICHARD M. MYERS18, JEREMY SCHM
18、UTZ18, MARK DICKSON18, JANE GRIMWOOD18 & DAVID R. COX18 University of Washington Genome Center: MAYNARD V. OLSON19, RAJINDER KAUL19 & CHRISTOPHER RAYMOND19 Department of Molecular Biology, Keio University School of Medicine: NOBUYOSHI SHIMIZU20, KAZUHIKO KAWASAKI20 & SHINSEI MINOSHIMA20 University o
19、f Texas Southwestern Medical Center at Dallas: GLEN A. EVANS21?, MARIA ATHANASIOU21 & ROGER SCHULTZ21 University of Oklahomas Advanced Center for Genome Technology: BRUCE A. ROE22, FENG CHEN22 & HUAQIN PAN22 Max Planck Institute for Molecular Genetics: JULIANE RAMSER23, HANS LEHRACH23 & RICHARD REIN
20、HARDT23 Cold Spring Harbor Laboratory, Lita Annenberg Hazen Genome Center: W. RICHARD MCCOMBIE24, MELISSA DE LA BASTIDE24 & NEILAY DEDHIA24 GBFGerman Research Centre for Biotechnology: HELMUT BL?CKER25, KLAUS HORNISCHER25 & GABRIELE NORDSIEK25,The Sequence of the Human Genome J. Craig Venter, Mark D
21、. Adams, Eugene W. Myers, Peter W. Li, Richard J. Mural, Granger G. Sutton, Hamilton O. Smith, Mark Yandell, Cheryl A. Evans, Robert A. Holt, Jeannine D. Gocayne, Peter Amanatides, Richard M. Ballew, Daniel H. Huson, Jennifer Russo Wortman, Qing Zhang, Chinnappa D. Kodira, Xiangqun H. Zheng, Lin Che
22、n, Marian Skupski, Gangadharan Subramanian, Paul D. Thomas, Jinghui Zhang, George L. Gabor Miklos, Catherine Nelson, Samuel Broder, Andrew G. Clark,4 Joe Nadeau, Victor A. McKusick, Norton Zinder, Arnold J. Levine, Richard J. Roberts,8 Mel Simon, Carolyn Slayman, Michael Hunkapiller, Randall Bolanos
23、, Arthur Delcher, Ian Dew, Daniel Fasulo, Michael Flanigan, Liliana Florea, Aaron Halpern, Sridhar Hannenhalli, Saul Kravitz, Samuel Levy, Clark Mobarry, Knut Reinert, Karin Remington, Jane Abu-Threideh, Ellen Beasley, Kendra Biddick, Vivien Bonazzi, Rhonda Brandon, Michele Cargill, Ishwar handramou
24、liswaran, Rosane Charlab, Kabir Chaturvedi, Zuoming Deng, Valentina Di Francesco, Patrick Dunn, Karen Eilbeck, Carlos Evangelista, Andrei E. Gabrielian, Weiniu Gan, Wangmao Ge, Fangcheng Gong, Zhiping Gu, Ping Guan, Thomas J. Heiman, Maureen E. Higgins, Rui-Ru Ji, Zhaoxi Ke, Karen A. Ketchum, Zhongw
25、u Lai, Yiding Lei, Zhenya Li, Jiayin Li, Yong Liang, Xiaoying Lin, Fu Lu, Gennady V. Merkulov, Natalia Milshina, Helen M. Moore, Ashwinikumar K Naik, Vaibhav A. Narayan, Beena Neelam, Deborah Nusskern, Douglas B. Rusch, Steven Salzberg, Wei Shao, Bixiong Shue, Jingtao Sun, Zhen Yuan Wang, Aihui Wang
26、, Xin Wang, Jian Wang, Ming-Hui Wei, Ron Wides, Chunlin Xiao, Chunhua Yan, Alison Yao, Jane Ye, Ming Zhan, Weiqing Zhang, Hongyu Zhang, Qi Zhao, Liansheng Zheng, Fei Zhong, Wenyan Zhong, Shiaoping C. Zhu, Shaying Zhao, Dennis Gilbert, Suzanna Baumhueter, Gene Spier, Christine Carter, Anibal Cravchik
27、, Trevor Woodage, Feroze Ali, Huijin An, Aderonke Awe, Danita Baldwin, Holly Baden, Mary Barnstead, Ian Barrow, Karen eeson, Dana Busam, Amy Carver, Angela Center, Ming Lai Cheng, Liz Curry, Steve Danaher, Lionel Davenport, Raymond Desilets, Susanne Dietz, Kristina Dodson, Lisa Doup, Steven Ferriera
28、, Neha Garg, Andres Gluecksmann, Brit Hart, Jason Haynes, Charles Haynes, Cheryl Heiner, Suzanne Hladun, Damon Hostin, Jarrett Houck, Timothy Howland, Chinyere Ibegwam, Jeffery Johnson, Francis Kalush, Lesley Kline, Shashi Koduru, Amy Love, Felecia Mann, David May, Steven McCawley, Tina McIntosh, Iv
29、y McMullen, Mee Moy, Linda Moy, Brian Murphy, Keith Nelson, Cynthia Pfannkoch, Eric Pratts, Vinita Puri, Hina Qureshi, Matthew Reardon, Robert Rodriguez, Yu-Hui Rogers, Deanna Romblad, Bob Ruhfel, Richard Scott, Cynthia Sitter, Michelle Smallwood, rin Stewart, Renee Strong, Ellen Suh, Reginald Thoma
30、s, Ni Ni Tint, Sukyee Tse, Claire Vech, Gary Wang, Jeremy Wetter, Sherita Williams, Monica Williams, Sandra Windsor, Emily Winn-Deen, Keriellen Wolfe, Jayshree Zaveri, Karena Zaveri, Josep F. Abril,4 Roderic Guig,4 Michael J. Campbell, Kimmen V. Sjolander, Brian Karlak, Anish Kejariwal, Huaiyu Mi, B
31、etty Lazareva, Thomas Hatton, Apurva Narechania, Karen Diemer, Anushya Muruganujan, Nan Guo, Shinji Sato, Vineet Bafna, Sorin Istrail, Ross Lippert, Russell Schwartz, Brian Walenz, Shibu Yooseph, David Allen, Anand Basu, James Baxendale, Louis Blick, Marcelo Caminha, John Carnes-Stine, Parris Caulk,
32、 Yen-Hui Chiang, My Coyne, Carl Dahlke, Anne Deslattes Mays, Maria Dombroski, Michael Donnelly, Dale Ely, Shiva Esparham, Carl Fosler, Harold Gire, Stephen Glanowski, Kenneth Glasser, Anna Glodek, Mark Gorokhov, Ken Graham, Barry Gropman, Michael Harris, Jeremy Heil, Scott Henderson, Jeffrey Hoover,
33、 Donald Jennings, Catherine Jordan, James Jordan, John Kasha, Leonid Kagan, Cheryl Kraft, Alexander Levitsky, Mark Lewis, Xiangjun Liu, John Lopez, Daniel Ma, William Majoros, Joe McDaniel, Sean Murphy, Matthew Newman, Trung Nguyen, Ngoc Nguyen, Marc Nodell, Sue Pan, Jim Peck, Marshall Peterson, Wil
34、liam Rowe, Robert Sanders, John Scott, Michael Simpson, Thomas Smith, Arlan Sprague, Timothy Stockwell, Russell Turner, Eli Venter, Mei Wang, Meiyuan Wen, David Wu, Mitchell Wu, Ashley Xia, Ali Zandieh, Xiaohong Zhu,“Whats Human Genome Project?” “One base One dollar!” - by a taxi driver (and a tax payer),全基因组已经测序的一些生物,21世纪分子生物学发展的趋势,功能基因组学 蛋白质组学 生物信息学,Discovery can not be planned - Antonie Danchin,Do your experiment, at least once a year! - Sydney Brenner,Thank you for your patience!,
