From Genetics to BioinformaticslDNA structure and its biological functionlThe Human GenomelThe Human Genome ProjectModern Biology Molecular Basis of InheritanceI. DNA structure and its biological functionMendel: The Father of Genetics1865 Gregor Mendel discover the basic rules of heredity of garden pea.复杂的生物学特征可以用数学规律来描述。复杂的生物学特征可以用数学规律来描述。What is these factor? And where are they located?CellChromosomeNuclein(Didnt know its function)DNA structure and its biological functionJohann MiescherJohann Miescher discovered DNA and named it nuclein.Major events in the history of Molecular Biology 1900-1911l1902 - Emil Fischer wins Nobel prize: showed amino acids are linked and form proteinsEmil Fischerintroduced formulas depicting the spatial arrangement of groups around chiral carbon atoms Fruit Fly：Finding the Genes1911 Thomas Morgan discovers genes on chromosomes are the discrete units of heredityThomas MorganMajor events in the history of Molecular Biology 1900-19111910-1925: Development of Cytological GeneticslCytogenetics is the study of chromosomes and chromosome abnormalities (畸形)lThe relationship between genes and proteins was first proposed by Garrod in 1908lGarrod, a prominent physician at St. Bartholomews Hospital in London, understood both the new science of biochemistry and the emerging discipline of geneticsInborn Errors of MetabolismnFollowing Mendels laws, Garrod concluded that alkaptonuria is a congenital disorder(先天性的变异), not the result of a bacterial infection as was commonly thought.nHe observed that inherited diseases reflect a patients inability to make a particular enzyme, which he referred to as “inborn errors of metabolism”Inborn Errors of MetabolismTetranucleotide HypothesisnPhoebus Levene (Russian-American, 1869-1940) nHe worked with Albrecht Kossel and Emil Fischer, the nucleic acid and protein experts at the turn of the 20th. CenturynThe simplicity of the structure implied that DNA was too uniform to contribute to complex genetic variationGeorge BeadleEdward TatumIdentify that genes make proteins, but what is gene?Major events in the history of Molecular Biology 1940 - 1950One gene-One enzyme HypothesisOne gene-One enzyme Hypothesis“Transforming Principle” identified as DNAAverys workThe Hershey-Chase ExperimentlThe Americans Alfred Hershey (1908-1997) and Martha Chase (1930-2003) published in 1952 a now classical paper.lErwin Chargaff showed (1950s):Amount of adenine relative to guanine differs among speciesAmount of adenine always equals amount of thymine and amount of guanine always equals amount of cytosine%A=%T and %G=%CEdwin Chagraff (1905-2002)Base RatiosX-ray Crystallography Applied to Nucleic AcidslBetween 1940s and 1950s: Maurice Wilkins (1916-) and Rosalind Franklin (1920-1958) worked on X-ray/DNA.lJames Watson (American, 1928-)lFrancis Crick (British, 1916-2004)Major events in the history of Molecular Biology 1952 - 1960PrincipleDataSourceX-ray crystallographyStacked layers of subunits in spirals; long chain, no ruling out of two chains, sugar-phosphate in the outsideWilkins and Franklin (but mostly Franklin)Organic chemistry4 nucleotidesLeveneBiochemistrya-helix, model buildingPaulingChromatographyBase ratiosChargaffChemical bondingRight form of the basesJ. DonahueMathematicsAttractive forces between DNA basesJ. GriffithEnter Watson and CrickInformational approach(transfer of information, translation of information)The central dogma of molecular biologyDNAmRNA(messenger)rRNA(ribosomal)tRNA(transfer)ProteinRibosometranscriptiontranscriptiontranscriptiontranslationMolecular biology is born1972 1972 Paul Berg Paul Berg and co-and co-workers create the first workers create the first recombinant DNA recombinant DNA molecule.molecule.Major events in the history of Molecular Biology 1970- 1977Proc Natl Acad Sci U S A. 1972 ,69(10):2904-2909. 19771977Allan Maxam Allan Maxam and and Walter Gilbert Walter Gilbert (pictured) at Harvard University (pictured) at Harvard University and and Frederick Sanger Frederick Sanger at the U.K. at the U.K. Medical Research Council (MRC) Medical Research Council (MRC) independently develop methods for independently develop methods for sequencing DNA ( sequencing DNA ( PNAS PNAS , , February; February; PNAS PNAS , December)., December). Maxam, A.M., Gilbert, W. Proc Natl Acad Sci, 74 (2): 560-4. 1977. A new method for sequencing DNA.GenBank Database Formedl1982,GenBank, NIHs publicly accessible genetic sequence database, was formed at Los Alamos National Laboratory. Scientists submit DNA sequence data from a wide range of organisms to GenBank; researchers routinely retrieve and analyze the data in the archive.Major events in the history of Molecular Biology 1980 - 19951983: First Disease Gene Mapped亨廷顿舞蹈病A genetic marker linked to Huntington disease was found on chromosome 4 in 1983, making Huntington disease, or HD, the first genetic disease mapped using DNA polymorphisms. A polymorphic DNA marker genetically linked to Huntingtons disease. Nature, 3