J Craig Venter s genome PLOS Biology 2007 mapping by linkage MCB140 09 07 07 1 Thomas Hunt Morgan the first nativeborn American to win the Nobel Prize founder of modern genetics MCB140 09 07 07 2 A 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 3 MCB140 09 07 07 4 Tough 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 5 May 1910 was when the revolution began Morgan found a white eyed male running around in one bottle MCB140 09 07 07 6 MCB140 09 07 07 7 Fig 4 20 MCB140 09 07 07 8 MCB140 09 07 07 9 Nothing special here Just like seed color in peas Normal Mendelian ratio 3 1 but where are the white eyed females MCB140 09 07 07 10 MCB140 09 07 07 11 Nettie Stevens discoverer of the 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 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 12 MCB140 09 07 07 13 MCB140 09 07 07 14 MCB140 09 07 07 15 MCB140 09 07 07 16 MCB140 09 07 07 17 Morgan 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 chromosomes MCB140 09 07 07 18 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 Discovered linkage Invented the terms allele heterozygous homozygous homeotic Bateson W 1916 The mechanism of Mendelian heredity a review Science 44 536 543 MCB140 09 07 07 19 Bridges Sturtevant Morgan Muller Calvin 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 Legacy MCB140 09 07 07 21 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 desk and told him to look for more mutations MCB140 09 07 07 22 Criss cross inheritance what normally happens white eyed sons and red eyed daughters of white eyed mothers and red eyed fathers Therefore a white eyed mother and a red eyed father cannot have a white eyed daughter MCB140 09 07 07 23 The exceptional female appears MCB140 09 07 07 24 Fig 13 28 MCB140 09 07 07 25 How could a white eyed mother have a white eyed daughter Note An XXY Drosophila is female An XXY human is male MCB140 09 07 07 26 Genetic evidence Bridges crossed those exceptional females to red eyed males and showed that all the classes of individuals expected from the outcome of a meiosis in this XXY female do in fact appear He also provided cytological evidence that the exceptional female is in fact exceptional MCB140 09 07 07 27 MCB140 09 07 07 28 Normal female White eyed daughters of an exceptional mother Extraordinarily precise concordance between the inheritance of chromosomes and particular traits argues that Mendel s factors of inheritance the genes lie on chromosomes MCB140 09 07 07 29 Genes lie on chromosomes What else is there to be found out The next two major advances in genetics both came from the study of apparent exceptions to Mendel s laws 1 Strong deviations from a 1 1 1 1 phenotyping ratio in a AaBb x aabb cross coupling and repulsion linkage genetic map 2 Highly aberrant phenotypic ratios e g 9 3 4 when for example brother sister mating black Labrador retrievers fathered by a black Dad and yellow Mom epistasis MCB140 09 07 07 30 Hmmmmm It was not long from the time that Mendel s work was rediscovered that new anomalous ratio began appearing One such experiment was performed by Bateson and Punnett with sweet peas They performed a typical dihybrid cross between one pure
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