1MCB140 01-29-07 1Genetics – the narrative so far1. Mendel (1853-66):1. Heredity operates via particles of information (=genes).2. For any trait, two particles (=alleles of a gene) come together in an organism, but then separate into gametes, one per gamete.3. This process occurs independently for particles (genes) for different traits.2. Häckel, Weissmann, Flemming, Boveri (1850-1900):1. The nucleus of the cell is the organelle that is reponsible for heredity (Hääckel, Boveri), and specific kinds of cells (the gametes) that are separate and distinct from the rest of the body, are responsible for generating progeny (Weissman).2. Inside the cell, lie the chromosomes (Flemming) that separate into daughter cells via mitosis.3. Proper development of an organism requires a specific set of a particular kind of chromosome (Boveri).3. Sutton (and Cannon) – 1902.1. There is a striking concordance between the behavior of Mendel’sparticles and chromosomes during meiosis.MCB140 01-29-07 2Genetics – the narrative to come1. Morgan and Bridges – genes lie on chromosomes (1910-1915).2. Bateson and Sturtevant (1906-15) – some genes appear to be physically linked; the nature of this linkage is the following: genes are arranged on a chromosome in a linear order, at particular distances from each other.3. McClintock and Stern (1930) – genetic recombination occurs when homologous chromosomes can exchange parts.4. Beadle and Tatum (1946) – some genes affect the development of traits by encoding biochemical functions (“one gene = one enzyme”).5. Muller (1927) – the gene can be purposefully mutated.6. Benzer – the gene itself can be split into smaller units.7. Studying the molecular makeup of life via:1. The genetic screen – use of purposeful mutagenesis to identify genes required for the development of various traits.2. Mapping by linkage and association mapping – the study of “simple” and “complex” traits by analysis of pedigrees and populations.MCB140 01-29-07 3What is being omitted for lack of time1. The rediscovery of Mendel’s laws by Correns, Tschermak, and de Vries.2. The finding – by Cuenot and by Castle –that Mendel’s laws also apply to mammals, such as mice and guinea pigs.MCB140 01-29-07 4William Bateson“… he privately subsidized his small book, Mendel’s Principles of Heredity: A Defence and he sent copies to all of the leading students of heredity to make sure that Mendel would not suffer another 35 years of neglect.” Carlson Mendel’s Legacy2MCB140 01-29-07 5Modified Mendelian ratios ÆepistasisMCB140 01-29-07 6“Repulsion and coupling”Æ linkageMCB140 01-29-07 7Bateson 1902MCB140 01-29-07 8Bateson 1902αλληλος = "each other"3MCB140 01-29-07 9Fig. 3.7MCB140 01-29-07 10Thomas Hunt Morgan, the first native-born American to win the Nobel Prize, founder of modern geneticsBridgesMullerMorganSturtevantMCB140 01-29-07 12Morgan et al. 1915“As will be shown now, certain factors follow the distribution of the X chromosome and are therefore supposed to be contained in them.”Emphasis mine – fdu. ↓Genes lie on chromosomes4MCB140 01-29-07 13“The supposition that particles of chromatin, indistinguishable from each other and indeed almost homogeneous under any known test, can by their material nature confer all the properties of life surpasses the range of even the most convinced materialism.”Bateson, W. (1916) The mechanism of Mendelian heredity (a review). Science, 44, 536-543. MCB140 01-29-07 14MCB140 01-29-07 15A problem and a solution“The value and utility of any experiment…” (Mendel)“What was needed to open up genetics to new phenomena was an organism that bred rapidly, produced lots of progeny, and was inexpensive to maintain” (Carlson)“Fruit flies can be raised on a mixture of corn meal, yeast, sugar, and agar. Flies complete their life cycle from fertilization to emergence of the adult fly in 10 days. A female can produce 3,000 progeny in her lifetime. A single male can sire well over 10,000 offspring.” (Hartwell)MCB140 01-29-07 16(aka chr. 1)Note: no crossing over in male meiosis!5MCB140 01-29-07 18Morgan and Drosophila(go Bears)Morgan was not a geneticist by training (he was an embryologist), and he was notthe first one to use Drosophila for purposes of genetic research (Castle was).“One of the baffling problems of breeders in pre-Mendelian days had been the effects of inbreeding and crossbreeding. What these were was a much-debated question. We set out to give it an experimental test andfound ready to hand a rapidly breeding little fly, Drosophila, being cultured in the laboratory by a graduate student as embryological material. This, he told us, would complete a generation within a fortnight. (Charles Woodworth, prof entomology at UC Berkeley). … We beganculturing the fly on pulped Concord grapes, but this gave us poor results as many of the larvae would get drowned and then our population statistics were no good. As grapes became out of season, we tried other fruits, and finally hit the jackpot in bananas. …The conclusion drawn [from our studies] was that inbreeding reduces very slightly theproductiveness of Drosophila. … This was not a conclusion of world-shaking importance. The important outcome of this investigation was that it called to Morgan’s attention a new source of material for experimental study not subject to the limitations of slow-breeding laboratory mammals.” WE Castle (prof genetics UC Berkeley) The Beginnings of Mendelism in America – in Genetics in the 20thCentury, p. 73.MCB140 01-29-07 19Tough early going“… Morgan had been working on fruit flies for at least two years before he found his most significant mutation, a white-eyed fly. For this new approach, Morgan was his own first student. He bred the fliles for two years without assistance. … He pointed to the shelves with flies and [said] that he had wasted two years and had gotten nothing for his work.”MCB140 01-29-07 20“May 1910 was when the revolution began. Morgan found a white-eyed male running around in one bottle.”6MCB140 01-29-07 21Great opening passages in the history of the English language“It is a truth universally acknowledged that a single man in possession of a good fortune must be in want of a wife.”“When Caroline Meeber boarded the afternoon train for Chicago, her total outfit consisted of a small trunk, a cheap imitation alligator-skin satchel, a small lunch in a paper box, and a
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