Thomas Hunt Morgan, the first native- Enter the fruit fly born American to win the Nobel Prize, founder of modern genetics MCB140 9-8-08 1 MCB140 9-8-08 2 Morgan et al. 1915 “As will be shown now, certain factors follow the distribution of the X chromosome and Morgan Bridges Muller are therefore supposed to be contained in them.” Emphasis mine – fdu. ↓ Genes lie on chromosomes Sturtevant MCB140 9-8-08 4 “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 9-8-08 5 MCB140 9-8-08 6 1 A problem and a solution (aka chr. 1) “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 Note: no crossing over in male meiosis! well over 10,000 offspring.” (Hartwell) MCB140 9-8-08 7 MCB140 9-8-08 8 Morgan and Drosophila (go Bears) Morgan was not a geneticist by training (he was an embryologist), and he was not the 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 and found 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 began culturing 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 the productiveness 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 20th Century, p. 73. MCB140 9-8-08 10 “May 1910 was when the revolution Tough early going began. Morgan found a white-eyed “… Morgan had been working male running around in one bottle.” 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 9-8-08 11 MCB140 9-8-08 12 2 One of the best-known 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.” MCB140 9-8-08 13 MCB140 9-8-08 14 “The Mechanism of Mendelian Heredity” (1915) Thomas Hunt Morgan Alfred Sturtevant Hermann Muller Calvin Bridges MCB140 9-8-08 15 MCB140 9-8-08 16 Nothing special here. Just like seed color in peas. Normal Mendelian ratio (3:1) – but where are the white-eyed females?!! MCB140 9-8-08 17 MCB140 9-8-08 18 3 MCB140 9-8-08 19 MCB140 9-8-08 20 Nettie Stevens, discoverer of the The useful mealworm sex chromosomes Nettie Stevens was one of the first female scientists to make a name for herself in the biological sciences. She was born in Cavendish, Vermont. Her family “It is perfectly clear that an egg settled in Westford, Vermont. Stevens' father was a carpenter and handyman. He did well enough to own quite a bit of Westford property, and could afford to send his children to school. fertilized by a spermatozoon Stevens was a brilliant student, consistently scoring the highest in her classes. In 1896, Stevens went to California to attend Leland Stanford University. She containing the smaller graduated with a masters in biology. Her thesis involved a lot of microscopic work and precise, careful detailing of new species of marine life. This training was a factor in her success with later investigations of chromosomal hererochromosome produces a behavior. After Stanford, Stevens went to Bryn Mawr College for more graduate work. male, while one fertilized by a Thomas Hunt Morgan was still teaching at Bryn Mawr, and was one of her professors. Stevens again did so well that she was awarded a fellowship to study abroad. She traveled to Europe and spent time in Theodor Boveri's lab spermatozoon containing the at the Zoological Institute at Wurzburg, Germany. Boveri was working on the problem of the role of chromosomes in heredity. Stevens likely developed an larger heterochromosome interest in the subject from her stay. In 1903, Stevens got her Ph.D. from Bryn Mawr, and started looking for a develops into a female.” research position. She was eventually given an assistantship by the Carnegie Institute after glowing recommendations from Thomas Hunt Morgan, Edmund Wilson and M. Carey Thomas, the president of Bryn Mawr. Her work on sex Æ XO is male and XX is female determination was published as a Carnegie Institute report in 1905. (until 1916) MCB140 9-8-08 21 MCB140 9-8-08 22 Edmund Wilson – arguably, the first Dr. Thomas Ried, NCI/NIH: SKY of hormal human cell XY person on Earth “In many species of insects there are two classes of spermatozoa, equal in number, which in the early stages of their development, differe visibly in respect to the nuclear constitution; while there is but one class of egg. … That is to say, if the two kinds of spermatozoa be designated as the X-class and the Y- class, respectively; the eggs are all of the X-class. The male may accordingly be designated as the heterogametic sex, the female as the homogametic.” MCB140 9-8-08 23 MCB140 9-8-08 24 4 MCB140 9-8-08 25 MCB140 9-8-08 26 MCB140 9-8-08 27 MCB140 9-8-08 28 MCB140 9-8-08 29 MCB140 9-8-08 30 5 Calvin Bridges … “raised by his grandparents in upstate New York, both of his parents dying young. He was a talented student buit his grandparents were poor and Bridges had to make do with clothing that was constantly mended. He was too ashamed to go to social activities in high school because of his ragged appearance. He received a scholarship to attend Columbia University, but he had to support himself with part-time work. Bridges took the same introductory biology course as Sturtevant, and Morgan, who learned of Bridges’ circumstances, asked him to be a part-time bottle-washer and food preparator for the fly work that was gaining momentum in Morgan’s laboratory.” Carlson Mendel’s Legacy MCB140 9-8-08 31 MCB140 9-8-08 32 vermilion “… Bridges’ circumstances changed approximately a year after he began working for Morgan. He showed Morgan a bottle that contained a fly whose eye color seemed to be brighter than usual. Morgan isolated the fly, showed that it carried another X-linked trait, and called that trait vermilion. He also assigned Bridges to a (A) Bridges (left) and Sturtevant in 1920. (B) Morgan in 1917. The photo of Morgan, desk and told him to look for more who was camera shy, was taken by Sturtevant using a camera hidden in an incubator mutations.” and operated remotely by means of a string. The books and microscope in the background were at Sturtevant's desk G. Rubin and E. Lewis Science 287: 2216. MCB140 9-8-08 33 MCB140 9-8-08 34 Criss-cross inheritance: white-eyed The “exceptional sons and red-eyed daughters of white- female” eyed mothers and red-eyed fathers appears MCB140 9-8-08 35 MCB140 9-8-08 36 6 MCB140 9-8-08 37 Fig. 13.28 MCB140 9-8-08 38 How could a white-eyed mother have a white-eyed daughter? Note: An XXY Drosophila is female. An XXY human is male. Y? MCB140 9-8-08 39 Fig. 4.21 MCB140 9-8-08 40 MCB140 9-8-08 41 MCB140 9-8-08 42 7 MCB140 9-8-08 43 MCB140 9-8-08 44 Normal female White-eyed daughters of an “exceptional” mother MCB140 9-8-08 45 MCB140 9-8-08 46 Bridges, C. B. 1935. Salivary chromosome maps with a key to the banding of the chromosomes of Drosophila melanogaster. J. Hered. 26: 60–64 MCB140 9-8-08 47 MCB140 9-8-08 48 8 Fine, fine, genes are on chromosomes. Now what? The next two major advances in genetics both came from the study of apparent exceptions to Mendel’s laws.