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HEREDITY

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Early Explanations for Heredity Genes and Chromosomes Structure of DNA Central Dogma of Molecular Biology PCR and Genome Sequencing

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Preformation Pre-existing All people who will be born have been formed The homunculus unfolds to form the adult Came from Egyptian alchemy Epigenesis Assembled Each person is put together by contributions of each parent The adult develops from an amorphous mass Came from Pythagoras and Aristotle

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Preformation More in line with western Christianity Leeuwenhoek and other early microscopists claimed to have seen the homunculus

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Epigenesis Later microscopists noted that certain tissues, like the apical meristems of plants, were made of a region of identical cells that developed into typical plant tissues. William Harvey (1578- 1657, England) stated that all animals came from eggs and they were fertilized by transference of hereditary material from the semen.

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Pangenesis Charles Robert Darwin (1809- 1882, Britain) Hereditary particles from all parts of the body are transported by the circulatory system and concentrated in the gametes. It began to take on a Lamarkian perspective and explain evolution by acquired characters Attempted to be confirmed by Francis Galton (1822-1911, Britain). Disproved

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Germ Plasm Theory Friedrich Leopold August Weismann (1834-1914, Germany) Hereditary particles retained only if needed as development progresses in somatic cells, but remains unchanged in germ plasm ~disproved by cloning.

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Hugo de Vries 1848-1936, Netherlands Modified pangenesis Called particles pangenes (shortened to genes later) Working on Evening Primrose noticed flower color either white or yellow in particular ratios Developed mutation theory of evolution In 1900 discovered papers published 30 years earlier by Gregor Johann Mendel Also discovered by Carl Correns (1864-1933, Germany) and Erich von Tschermak (1871-1962, Austria)

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Gregor Johann Mendel 1822-1884, Austrian Empire (now Czech Republic) Joined Augustinian Order and took name Gregor Studied physics under Doppler Failed teaching exam (oral portion) and became an administrator of monastery of Brnn (Brno in Czech) Became interested in heredity and began to study mice but abbot uncomfortable having a monk who studied sex; so, Mendel began to study peas and looked at 7 traits that seemed to be independent of each other.

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Communicated with Carl Wilhelm von Ngeli (1817-1891, Switzerland). Theory of ideoplasm (a portion of the cytoplasm that carried hereditary information) Commented to Mendel: your paper is of some interest but is too empirical to be important to the science of heredity. Advised him to work on animals instead

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Law of Segregation Dominant and recessive phenotypes. (1) Parental generation. (2) F 1 generation. (3) F 2 generation. Dominant (red) and recessive (white) phenotype look alike in the F 1 (first) generation and show a 3:1 ratio in the F 2 (second) generation.

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Law of Independent Assortment Dihybrid cross. The phenotypes of two independent traits show a 9:3:3:1 ratio in the F 2 generation. In this example, coat color is indicated by B(brown, dominant) or b (white), while tail length is indicated by S (short, dominant) or s (long). When parents are homozygous for each trait (SSbb andssBB), their children in the F 1 generation are heterozygous at both loci and only show the dominant phenotypes. If the children mate with each other, in the F 2 generation all combinations of coat color and tail length occur: 9 are brown/short (purple boxes), 3 are white/short (pink boxes), 3 are brown/long (blue boxes) and 1 is white/long (green box).

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Genes and Chromosomes Walter Stanborough Sutton (1877-1916, USA) Noted that the segregation and independent assortment of grasshopper chromosomes during meiosis conformed to Mendels Laws (1900-1903) Thus Genes must be located on the chromosomes Theodor Heinrich Boveri (1862- 1915, Germany) independently came to the same conclusion

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Chromosomes and Fruit Flies T. H. (Thomas Hunt) Morgan (1966-1945, USA) Began to study mutations in fruit flies after rediscovery of Mendels Laws Sought out mutant forms Discovered sex-linked traits and began to map chromosomes by cross-over distance

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Mutations and Fruit Flies H. J. (Hermann Joseph) Muller (1890- 1967, USA, USSR, Britain) Followed Morgan and worked on fruit flies Induced mutations by high temperature, X- rays

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What is the gene made of? Oswald Theodore Avery (1877-1955, Canada, USA) Showed that DNA moved from one bacterium to another could transform a benign strain to a virulent strain in 1940s

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Hershey and Chase (1952) Alfred Day Hershey (1908-1997, USA) and Martha Cowles Chase (1927-2003, USA)

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Structure of DNA (1953) James Dewey Watson (1928-, USA) Francis Harry Compton Crick (1916-2004, Britain & USA Maurice Hugh Frederick Wilkins (1916-2004, New Zealand & Britain) Rosalind Elsie Franklin (1920-1958, Britain)

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Central Dogma of Molecular Biology Francis Crick (1958) Sequence of information transfer

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Decoding DNA Marshall Warren Nirenberg (1927-2010, USA) Began to perform simple (conceptually) experiments to generate polypeptides by using RNA sequences of UUU (generated poly phenylalanine) AAA(generated poly lysine) CCC(generated poly proline)

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The Codon George Gamow proposed that 3 bases would serve to unambiguously code for the 20+ different amino acids to code for particular polypeptides

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HIV and Reverse Transcriptase

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Polymerase Chain Reaction Developed in 1983 by Kary Banks Mullis (1944, USA)

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Genome Sequencing John Craig Venter (1946, USA) Employed shotgun method to sequence DNA with private company in competition with the Human Genome Project Long chains broken randomly Small pieces sequenced Then small sequences reassembled Method brought Human Genome Project in years ahead of schedule and billions under budget. Known recently for creating artificial life with assembled genome. Whole Genome Shotgun Sequencing Hierarchical Shotgun Sequencing

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Human Genome Project James Watson was the first director (1988-1992) Human genome has ~20,500 genes International effort begun in 1980s using PCR Strong effort begun in 1990 Separate genome into pieces ~150,000bp and sequence Look for start/stop codes 1 st draft published 2000 Completed genome 2003 By 2009, a personal genome could be completed for less than $2,000

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