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Lecture 11

L & S C30Y Lecture 11: Lecture 11

8 Pages

Letters And Science
Course Code
L & S C30Y
Urnov Fyodor

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find more resources at Lecture 11 2/24/2017 1:42:00 PM The awesome power of genetics “One gene = one enzyme”  probably the second most important genetic experiment after Mendel  The Beadle-Tatum Experiment o Can one isolate mutants in biochemical processes? o Specifically, a mutant that will not grow without a specific amino acid? o Step 1: Mutagenesis  Wild type(x-rays) mutagenized conidiacrossed with wild type of opposite mating typefruiting bodiesmicroscopic ascospores are dissected and transferred one by one to culture tubes. o Step 2: Screening for mutants o Beadle and Tatum deduced that each mutation that generated a nutrient requirement was inherited as a single-gene mutation because each gave a 1:1 ratio when crossed with a wild type. o Conclusion: there is a gene in the Neurospora genome that is responsible for the biosynthesis of the amino acid arginine. Yeast can live as haploid or diploid cells  Haploid yeast grow, mitotically, just fine.  They exist in two sexes, which yeast biologists do not call sexes, and instead call “mating types”  Two haploid yeast cells of different mating type can fuse, and form a diploid.  That diploid can do one of two things o Grow mitotically, as a diploid o Go through meiosis, and form 4 haploid cells, each of which can go back to living as haploid cells A useful term—prototrophic  Capable of synthesizing everything necessary from simple salts  Antonym: auxotrophic—needing a specific nutrient for growth. find more resources at find more resources at  E.g. Humans are auxotrophic for lysine, we cannot live without it in the diet  E. Coli is prototrophic for lysine, it can make it just fine.  Neurospora is really prototrophic. It will grow in inorganic salts and one vitamin. How the “genes for long life” were found Caenorhabditis elegans and Sydney Brenner  “Model organism” (sort of like model citizen):  Worm—small o Cheap to grow o Eats bacteria o Hermaphrodite—easy genetics o Transparent—can see cells o Adult animal composed of a defined number of cells, and can identify which cell came from which cell during development. o Has interesting behaviors that can be studied. o Dies after 2 weeks A correction  The radiolab folks say that Cynthia Kenyon found the “grim reaper” gene by “stumbling upon it by pure luck.”  Nothing could be further from the truth.  She did this in highly targeted fashion.  Worm: 19,735 protein-coding genes  And all this BIOLOGY—it does all these things!!!! It develops into a worm from a single egg, it eats, it mates, it moves around, etc.  Which genes are behind which feature of its biology? Insulin—the hormone of the well-fed state Let’s be very clear  In worms, there’s one insulin IGF-1 Pathway  During evolution, things diverged, so in us (and in mice) there are TWO pathways find more resources at find more resources at  Insulin itself—metabolism—mutations in animals strongly adversely affect lifespan, but there’s an interesting exception in humans.  IGF—growth and development—mutations increase lifespan. Cell signaling as a social network  NOT LIKE THIS: o Person A  Person B  Person C  LIKE THIS: o Person A  All person A’s friends  all their friends  snowballs The goal is a > millionfold amplification of signal  ~1 gram of sugar per liter of blood.  Five liters total of blood  During rapid sudden exercise, need to pour more glucose into bloodstream like a fire hose, but it’s not stored as powdered glucose  The hormone is a million times less abundant than the sugar. Four outstanding questions regarding insulin / IGF-1 and longevity  What biological mechanism explains the fact that mutants in this pathway affect lifespan? o A shift of physiology toward cell protection / maintenance / stress resistance.  Is there a connection between this pathway and the fact that caloric restriction affects lifespan? (Insulin—food, duh!
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