J. Craig Venter’s genome PLOS Biology 2007Thomas Hunt Morgan, the first native-born American to win the Nobel Prize, founder of modern geneticsA problem and a solutionSlide 4Tough early going“May 1910 was when the revolution began. Morgan found a white-eyed male running around in one bottle.”Slide 7Slide 8Slide 9Slide 10Slide 11Nettie Stevens, discoverer of the sex chromosomesSlide 13Slide 14Slide 15Slide 16Slide 17Morgan et al. 1915Slide 19Slide 20Calvin BridgesvermilionCriss-cross inheritance (what normally happens): white-eyed sons and red-eyed daughters of white-eyed mothers and red-eyed fathersThe “exceptional female” appearsSlide 25How could a white-eyed mother have a white-eyed daughter?Slide 27Slide 28Slide 29Genes lie on chromosomes. What else is there to be found out?HmmmmmWhat happened to Mendel’s 2nd law?!Morgan’s observation of linkageClearly not 1:1:1:1These two loci do not follow Mendel’s second law because they are linked (=lie relatively close to each other on the same chromosome)Slide 36Slide 37Batrachoseps attenuatus California Slender SalamanderSlide 39Slide 40Slide 41Slide 42A concept that brings “simple” and “influential” to new shades of meaningRecombination Frequency (Morgan’s data)Recombination frequency a genetic map (Sturtevant’s data)Slide 46Slide 47Slide 48Slide 49The three-point testcrossSlide 51Sturtevant’s remarkably simple and elegant argumentHow to Map Genes Using a Three-Point TestcrossSlide 541. Rename and rewrite cross2. Rewrite dataSlide 573. Determine gene order3b. Determine gene order4. E and F4b. F and N4c. E and N5. The map (ta-daaa!)Slide 64Who is this?What did Friedrich Miescher do?Slide 67A questionMCB140 09-07-07 1J. Craig Venter’s genomePLOS Biology 2007“mapping by linkage”MCB140 09-07-07 2Thomas Hunt Morgan, the first native-born American to win the Nobel Prize, founder of modern geneticsMCB140 09-07-07 3A problem and a solution“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)“The value and utility of any experiment…” (Mendel)“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 09-07-07 4MCB140 09-07-07 5Tough early going“… For this new approach, Morgan was his own first student. He bred the flies 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 09-07-07 6“May 1910 was when the revolution began. Morgan found a white-eyed male running around in one bottle.”MCB140 09-07-07 7MCB140 09-07-07 8Fig. 4.20MCB140 09-07-07 9MCB140 09-07-07 10Nothing special here.Just like seed color in peas.Normal Mendelian ratio (3:1) – but where are the white-eyed females?!!MCB140 09-07-07 11MCB140 09-07-07 12Nettie Stevens, discoverer of the sex chromosomesNettie 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 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.Stevens was a brilliant student, consistently scoring the highest in her classes. In 1896, Stevens went to California to attend Leland Stanford University. She 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 behavior.After Stanford, Stevens went to Bryn Mawr College for more graduate work. 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 at the Zoological Institute at Wurzburg, Germany. Boveri was working on the problem of the role of chromosomes in heredity. Stevens likely developed an interest in the subject from her stay.In 1903, Stevens got her Ph.D. from Bryn Mawr, and started looking for a 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 determination was published as a Carnegie Institute report in 1905.MCB140 09-07-07 13MCB140 09-07-07 14MCB140 09-07-07 15MCB140 09-07-07 16MCB140 09-07-07 17MCB140 09-07-07 18Morgan et al. 1915“Certain factors follow the distribution of the X chromosome and are therefore supposed to be contained in them.”Emphasis mine – fdu. ↓Genes lie on chromosomesMCB140 09-07-07 19“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. Discovered linkage.Invented the terms “allele, heterozygous, homozygous, homeotic.”BridgesMullerMorganSturtevantMCB140 09-07-07 21Calvin Bridges… “raised by his grandparents in upstate New York, both of his parents dying young. He was a talented student but 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 LegacyMCB140 09-07-07 22vermilion“… 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
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