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第六章 遺傳和遺傳物質(zhì),授課教師:牛登科 /teachers/niudk.htm Charles Darwin,When Charles Darwin proposed his theory of evolution in 1859, one of its major problems was the lack of an underlying mechanism for heredity. Darwin believed in a mix of blending inheritance and the inheritance of acquired traits (pangenesis). Blending inheritance would lead to uniformity across populations in only a few generations and thus would remove variation from a population on which natural selection could act. This led to Darwin adopting some Lamarckian ideas in later editions of On the Origin of Species and his later biological works. The inheritance of acquired traits was shown to have little basis in the 1880s when August Weismann cut the tails off many generations of mice and found that their offspring continued to develop tails.,/wiki/Gregor_Mendel Gregor Mendel was inspired by both his professors at the University of Olomouc (i.e. Friedrich Franz & Johann Karl Nestler) and his colleagues at the monastery (e.g., Franz Diebl) to study variation in plants, and he conducted his study in the monasterys 2 hectare experimental garden. Between 1856 and 1863 Mendel cultivated and tested some 29,000 pea plants (i.e., Pisum sativum). His experiments led him to make two generalizations, the Law of Segregation and the Law of Independent Assortment, which later became known as Mendels Laws of Inheritance. When Mendels paper was published in 1866 in Verhandlungen des naturforschenden Vereins Brnn, it was seen as essentially about hybridization rather than inheritance and had little impact and was cited about three times over the next thirty-five years.,Gregor Mendel Father of genetics,After completing his work with peas, Mendel turned to experimenting with honeybees to extend his work to animals. He produced a hybrid strain, but failed to generate a clear picture of their heredity because of the difficulties in controlling mating behaviors of queen bees. He also described novel plant species, and these are denoted with the botanical author abbreviation “Mendel“. After he was elevated as abbot in 1868, his scientific work largely ended, as Mendel became consumed with his increased administrative responsibilities, especially a dispute with the civil government over their attempt to impose special taxes on religious institutions. After his death, the succeeding abbot burned all papers in Mendels collection, to mark an end to the disputes over taxation.,Gregor Mendel Father of genetics,Mendels work was rejected at first, and was not widely accepted until after he died. By 1900, research aimed at finding a successful theory of discontinuous inheritance rather than blending inheritance led to independent duplication of his work by Hugo de Vries and Carl Correns, and the rediscovery of Mendels writings and laws. Though Erich von Tschermak was originally also credited with rediscovery, this is no longer accepted because he did not understand Mendels laws.,Rediscovery of Mendels work,The synthesis, produced between 1936 and 1947, reflects the consensus about how evolution proceeds. The previous development of population genetics, between 1918 and 1932, was a stimulus, as it showed that Mendelian genetics was consistent with natural selection and gradual evolution. The modern synthesis solved difficulties and confusions caused by the specialization and poor communication between biologists in the early years of the 20th century. At its heart was the question of whether Mendelian genetics could be reconciled with gradual evolution by means of natural selection. A second issue was whether the broad-scale changes (macroevolution) seen by palaeontologists could be explained by changes seen in local populations (microevolution). The synthesis included evidence from biologists, trained in genetics, who studied populations in the field and in the laboratory. The synthesis drew together ideas from several branches of biology which had become separated, particularly genetics, cytology, systematics, botany, morphology, ecology and paleontology. Julian Huxley invented the term in his book, Evolution: The Modern Synthesis (1942). Other major figures include R. A. Fisher, Theodosius Dobzhansky, J. B. S. Haldane, Sewall Wright, E. B. Ford, Ernst Mayr, Bernhard Rensch, Sergei Chetverikov, George Gaylord Simpson, and G. Ledyard Stebbins.,Modern evolutionary synthesis,1865: Gregor Mendels paper, Experiments on Plant Hybridization 1869: Friedrich Miescher discovers a weak acid in the nuclei of white blood cells that today we call DNA 1880 - 1890: Walther Flemming, Eduard Strasburger, and Edouard van Beneden elucidate chromosome distribution during cell division 1903: Walter Sutton and Theodor Boveri hypothesizes that chromosomes, which segregate in a Mendelian fashion, are hereditary units 1908: Hardy-Weinberg law derived. 1910: Thomas Hunt Morgan shows that genes reside on chromosomes 1913: Alfred Sturtevant makes the first genetic map of a chromosome: linear arranged genes,Classical genetics,1918: Ronald Fisher publishes “The Correlation Between Relatives on the Supposition of Mendelian Inheritance“ the modern synthesis of genetics and evolutionary biology starts. The origin of population genetics. 1928: Frederick Griffith discovers that hereditary material from dead bacteria can be incorporated into live bacteria 1941: Edward Lawrie Tatum and George Wells Beadle show that genes code for proteins;,Classical genetics,1944: Avery et al showed DNA as the genetic material 1948: Barbara McClintock discovers transposons in maize 1950: Erwin Chargaff shows that the amount of adenine, A, tends to be equal to that of thymine, T; and C=G. 1952: The Hershey-Chase experiment proves the genetic information of phages (and all other organisms) to be DNA 1953: DNA structure is resolved to be a double helix by James D. Watson and Francis Crick 1958: The Meselson-Stahl experiment demonstrates that DNA is semiconservatively replicated,Genetic: the DNA era,1961 - 1967: Combined efforts of scientists “crack“ the genetic code, including Marshall Nirenberg, Har Gobind Khorana, Sydney Brenner & Francis Crick 1964: Howard Temin showed using RNA viruses that the direction of DNA to RNA transcription can be reversed 1970: Restriction enzymes were discovered in studies of a bacterium, Haemophilus influenzae, enabling scientists to cut and paste DNA,Genetic: the DNA era,1972: Walter Fiers and his team determined the sequence of a gene: the gene for bacteriophage MS2 coat protein 1976: Walter Fiers and his team determine the complete nucleotide-sequence of bacteriophage MS2-RNA 1977: DNA is sequenced for the first time by Fred Sanger, Walter Gilbert, and Allan Maxam working independently. Sangers lab sequence the entire genome of bacteriophage -X174. 1983: Kary Banks Mullis invents the polymerase chain reaction enabling the easy amplification of DNA 1989: The human gene that encodes the CFTR protein was sequenced by Francis Collins and Lap-Chee Tsui. Defects in this gene cause cystic fibrosis.,Genetics: The genomics era,1995: The genome of bacterium Haemophilus influenzae is the first genome of a free living organism to be sequenced 1996: Saccharomyces cerevisiae, a yeast species, is the first eukaryote genome sequence to be released 1998: The first genome sequence for a multicellular eukaryote, Caenorhabditis elegans, is released 2001: First draft sequences of the human genome are released simultaneously by the Human Genome Project and Celera Genomics. 2003 (14 April): Successful completion of Human Genome Project with 99% of the genome sequenced to a 99.99% accuracy. 2012: The Encyclopedia of DNA Elements (ENCODE) project revealed that 80% of human genome is active.,Genetics: The genomics era,The part of the human DNA that has long been best understood is around 20,000 protein-coding genes. These genes, however, make up in total only around 1.5% of the DNA, and are separated from each other by long stretches of DNA that does not code for proteins. This remaining DNA includes the so-called regulome, which comprises a variety of DNA elements that in one way or another modulate the expression of protein-coding genes. It has not been clear, though, how much of the total DNA is comprised within the regulome. Until recently, the majority view has been that much of the DNA is “junk“DNA that is never transcribed and has no biological function. The central goal of the ENCODE project is to map out the regulome, by determining which parts of the DNA belong to it and the mechanisms by which those parts influence gene transcription. The ENCODE Consortium reported that they were able to assi

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