Topic 1 (BMMB554)

Slides covering Topic 1: From Mendel to Sanger. Slides for BMMB554 on-line course held at Penn State in Fall of 2015

Transcript

1. Topic 1 From Mendel to Sanger (with some detours) Images are from Wikipedia unless otherwise noted
2. …let’s see why we are here… Inspired by Mike Schatz
3. Cost per genome NHGRI
4. Sequencers worldwide OmicsMap
5. What’s a Petabyte? Unit Size Byte 1 Kilobyte 1,000 Megabyte 1,000,000 Gigabyte 1,000,000,000 Terabyte 1,000,000,000,000 Petabyte 1,000,000,000,000,000 Technically a Kilobyte is 210 (1,024) and a Petabyte is 250 (1,125,899,906,842,624) bytes
6. What’s a Petabyte? • 100 Gb = 1 Genome; 1Pb = 10,000 genomes • 1 Pb = 200,000 DVDs • 200,000 DVDs = 787 ft of DVDs (1/6 mile) • 1 Pb = 125 8Tb HDs (~$75,000) Technically a Kilobyte is 210 (1,024) and a Petabyte is 250 (1,125,899,906,842,624) bytes
7. Mike Schatz DNA data growth
8. What’s a Zettabyte? Unit Size Megabyte 1,000,000 Gigabyte 1,000,000,000 Terabyte 1,000,000,000,000 Petabyte 1,000,000,000,000,000 Exabyte 1,000,000,000,000,000,000 Zettabyte 1,000,000,000,000,000,000,000 Technically a Kilobyte is 210 (1,024) and a Petabyte is 250 (1,125,899,906,842,624) bytes
9. What’s a Zettabyte? • 100 Gb = 1 Genome; 1ZB = 10,000,000,000 genomes • 1 ZB = 200,000,000,000 DVDs • 200,000,000,000 DVDs = 1,500 miles • All of YouTube is ~200 Pb Technically a Kilobyte is 210 (1,024) and a Petabyte is 250 (1,125,899,906,842,624) bytes
10. Mike Schatz
11. So, how did it get started?
12. Books to consider
13. What is inheritance? ‣ Hippocrates ‣ Aristotle ‣ Charles Darwin ‣ Francis Galton
14. Hippocrates Both parents contribute to the offspring ca. 460 - 370 BC
15. Aristotle Only male contribution is important. Female merely provides “scaffolding” and “warmth”. 384 - 322 BC
16. Charles Darwin Provisional theory of pangenesis. All sperm, egg, buds consisted of multitude of gemmules given off by “each separate atom of the organism”. 1809 - 1882
17. Francis Galton Blood transfusion in rabbits produces no evidence to support provisional theory of pangenesis. 1822 - 1911
19. Gregor Johann Mendel 1822 - 1884 ‣ Born in Austro-Hungarian Empire (1822) ‣ Admitted at the Augustinian monastery in Brno (1843) ‣ Studies in Vienna with Doppler, Ettinghausen, Redtenbacher, Fenzl, and Unger (1851 - 1853) ‣ Teaches at the Monastery (1853 - 1868) ‣ Grows 28,000 plants and analyzed seven pairs of traits
20. Gonick & Whellis 1991
21. Magner 2002
22. Gonick & Whellis 1991
23. Sturtevant 1965
24. deVreis/Correns/Tschemak 1864-1935 1871-1962 The Rediscovery 1848-1935
25. Cuénot/Bateson/Johannsen 1861 - 1926 1857 - 1927 Confirmation in animals. Genetics, zygote, homozygote, heterozygote, gene, genotype, phenotype 1866 - 1951
26. State of chromosomal affairs in early 1900s ‣ Species have a constant number of chromosomes ‣ Equal numbers come from egg and sperm ‣ Reduction is accomplished by divisions ‣ Chromosomes are bearers of hereditary material
27. The Fly Room ‣ T. H. Morgan ‣ Frans-Alfons Janssen ‣ A. H. Sturtevant ‣ C. B. Bridges ‣ H. J. Muller
28. Carlson 2004
29. Muller/Bridges/Sturtevant 1889-1936 1891-1970 Elaboration of chromosomal theory | Induced mutations 1890-1967
30. Mendelism-Morganism ‣ Chromosomes contain hereditary information ‣ Genes are linearly distributed along chromosome ‣ Gene is a unit of information ‣ Gene can define characteristics such as eye color, wing shape etc.
31. But what is the chemical nature of heredity? ‣ Miescher | nucleic acids ‣ Kossel | DNA, RNA, histones ‣ Levene | tetranucleotide theory ‣ Chargaff | parity rules ‣ Griffith, Avery, MacLeod, McCarty | nucleic acid is the transforming factor
32. Friedrich Miescher Analysis of puss cells nuclei yielded nuclein, a compound with high phosphorus content that is resistant to pepsin. 1844 - 1895
33. Albrecht Kossel Five amino-organic compounds adenine, guanine, thymine, cytosine, uracil). Thymus nucleic acid (DNA) and yeast nucleic acid (RNA). 1858 - 1927 (NP 1910)
34. Phoebus Levene Fundamental work in biochemistry. DNA contains equal amount of all four bases organized as an unchangeable sequence of tetranucleotide units. 1869 - 1940
35. 1910 — 1930
    Dark age of molecular biology
36. 1879 - 1941 1877 - 1955 1909 - 1972 Transforming agent is a highly polymerized form of desoxyribonucleate 1911 - 2005 Griffith, Avery, MacLeod, McCarty
37. Griffith, Avery, MacLeod, McCarty
38. Erwin Chargaff The four DNA bases are NOT in equal amount but follow rules such the ratio of purines to pyrimidines is ~ 1 1905 - 2002
39. The Church of Phage ‣ Delbrück, Luria, Hershey | replication and genetic structure of viruses ‣ Lwoff | profage and lysogeny ‣ Lederberg, Hayes | bacterial sex, plasmids ‣ Hershey, Chase | DNA = heredity ‣ Watson | ...
40. 1906 - 1981 1912 - 1991 “discoveries concerning the replication mechanism and genetic structure of viruses”. 1908 - 1997 Delbrück, Luria, Hershey (NP 1969)
41. Delbrück-Luria experiment Mutations are stochastic
42. Hershey-Chase experiment
43. DNA ‣ Crick, Franklin, Watson, Wilkins | the structure of DNA ‣ Meselson, Stahl | semiconservative replication ‣ Ochoa, Kornberg | enzymatic synthesis of nucleic acids ‣ Holley, Nirenberg, Khorana | the code
44. 1916 - 2004 1920 - 1958 1916 - 2004 DNA is an antiparallel double helix b. 1928 Crick, Franklin, Watson, Wilkins (NP 1962)
45. Watson & Crick Franklin & Gosling Wilkins, Stockes, Wilson
46. b. 1930 b. 1929 DNA replication is semiconservative Meselson, Stahl
47. Meselson-Stahl experiment CsCl gradient centrifugation
48. Meselson & Stahl 1958
49. 1905 - 1993 1918 - 2007 Enzymes for RNA and DNA synthesis Ochoa, Kornberg (NP 1959)
50. 1922 - 1993 tRNA, 64 codons Holley, Khorana, Nirenberg (NP 1959) 1922 - 2011 1927 - 2010
51. Gene function ‣ Lwoff, Jacob, Monod | genetic map and gene regulation ‣ Beadle, Tatum | one gene = one protein ‣ Pauling, Ingram | molecular disease
52. 1902 - 1994 Lysogeny, prophage, genetic maps, gene regulation Lwoff, Jacob, Monod (NP 1965) b. 1920 1910 - 1976
54. Blender again... Elie Wollman (1917-2008)
55. 1903 - 1989 1909 - 1975 One gene one enzyme Beadle, Tatum (NP 1958)
57. 1901 - 1994 1924 - 2006 Sickle cell anemia is first molecular disease Pauling, Ingram
58. Reverse Transcription, Recombinant Age ‣ Temin, Baltimore | reverse transcription ‣ Cohen, Boyer | recombinant methodologies ‣ Berg | SV40 and rDNA ‣ Maxam, Gilbert, Sanger | sequencing is here
61. b. 1944 PCR Kary Mullis