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Themes in the Development of DNA Science A short history of Molecular Biology Ancient Wine Server Biotechnology is not new Production of bread, beer and wine along with cheese and yogurt predate modern record keeping X-Ray crystallography Max Delbruck: The intellectual father of molecular biology He and other quantum physists applied the principles of physical science research to biology and made molecular biology into a rigorous discipline You must know how moleculs react in a test tube in order to understand how they respond in vivo. William Harvey (1640) Demonstrates that organs work together as a system to circulate blood in the body Linus Pauling uses X-ray crystallography to deduce the structure of proteins April 25th 1953 Biotechnology begins formally James Watson and Francis Crick demonstrate their model of the DNA molecule Swedish biologist Carl Linnaeus Set up a hierarchy for classifying living things Charles Darwin The publication in 1869 of Darwin’s Origin of the Species marked the first step in the biological revolution that culminated a century later in Watson’s and Crick’s structure of DNA 1) There is a natural selection, over great periods of time, for the “fittest” forms of life. 2) 2) Natural selection arises from the competition for limited food and other resources among members of the same species. Only the fittest members of the population survive to reproduce. 3) 3) On rare occasions, a random physical change increases an individual’s ability to adapt to environmental conditions and/or exploit new food resources. This “adaptive” changge increases the individual’s chances to survive and to reproduce. 4) Adaptive changes are passed on to offspring as part of their hereditary endowment. These individuals are, in turn, fitter that their peers and survive to pass on their physical characteristics to succeeding generations. 5) Through the process of adaptive radiation, populations of organisms evolve to exploit specialized food resources, thus limiting competion and increasing chances for survival. Gregor Mendel Mendel’s paper published in 1865 provided the basis for the mathematical analysis of inheritance. From the results of controlled crosses of garden peas, he showed that traits are inherited in a predictable manner as discrete bits of genetic information, or “factors” Mendels Laws: Law of Segregation Parental genes for each trait segregate so that each sex cell contains only one sort. Thus, each contrasting member of a gene pair is equally likely to occur in gametes: C or cand P or p Law of Independent Assortment Genes for different traits assort into gametes independent of one another. Thus, each combination of genes is equally likely to occur: CP. Cp, cP or cp Mendel’s work lay unrecognized until 1900 when Hugo de Vries rediscovered Mendel’s paper and published research data that proved his work. Walter Suttonc 1902 He was the first to study chromosome behavior. This formed the basis of Chromosome theory Direct evidence to support chromosome theory was shown by Edmund Wilson. He showed that sex is determined by separate X and Y chromosomes. Femaleness is characterized by two copies of the x (XX) and maleness to a single x and a single y (XY) Thomas Hunt Morgan Established the lowly Fruit fly as the organism of choice for genetic research The random appearance of a single male white eyed fruit fly established forever the importance of an observable mutation or variation from the norm, as the starting point for genetic research. Edward Tatum George Beadle Use mold and induced mutations to show genes mediate cellular chemistry Fred Griffith and his mouse experiment Oswald Avery His experiment clearly showed that DNA was the hereditary molecule but scientists of the time dismissed his work because DNA was too “simple” to be the source of genetic variation. Hershey Chase Experiment Hershey Chase experiment 1) Most of the phage DNA remains with the bacterial cells. 2) Most of the phage protein is found in the supernate fluid. 3) Most of the initially infected bacteria (in the cell pellet) remain competent to produce phage. 4) If thew mechanical stirring is omitted, both protein and DNA sdediment with the bacteria 5) The phage protein removed from the cells by stirring constantly consists of more or less intact, empty phage coats, which may therefore be thought of as passive vehicles for the transport of DNA from cell to cell and having performed that task, play no further role in phage growth. The physical arrangement of atoms within DNA was made possible the development of Xray crystallography pioneered by Linus Pauling It was Rosalind Franklin’s Xray crystallography that ultimately showed the structure of DNA Watson and Crick did not acknowledge her contribution and she did not receive the Nobel Prize. She died from the radiation exposure incurred in her research Arthur Kornberg Discovered the enzymatic mechanism of DNA replication He purified an enzyme from E, coli, called DNA polymerase I He found that synthesis only occurs in the presence of a DNA template How Does DNA Structure describe Protein Synthesis? 1) The sequence hypothesis stated that DNA sequence and protein sequence are colinear. Genetic information must therefore be arrayed in a strickly loinear fashion along thwe length of the DNA molecule 2) The “central dogma” stated that gwentic information stored in DNA flows through RNA to proteins. RNA is the intermediate translator of the genetic code. Cracking the Code Marshall Nirenberg cracks the genetic code in 1966 By producing polypeptides in vitro they confirmed that the DNA code is in triplet form Ammendments to the Central Dogma 1) Some organisms do not use DNA as the storage molecule for the genetic code. RNA viruses store genetic info as RNA Genes are not immutably fixed on the chromosomes. Transposable genetic elements move around from one chromosome to another and may act as molecular switches to regulate gene expression. DNA sequence and protein sequence are not entirely colinear. The RNA transcript is often extensively editted prior to protein synthesis RNA has catalytic abilities previously attributed only to proteins. Self-replicating RNMA may have preceded DNA in molecular evolution. Depending on precisely hwere transcription begins, a single DNA sequence can be read in several overlapping “reading frames” of codons, which may translate into different polypeptides.