1. The DNA Story Germs, Genes, and Genomics 4

2. Heredity Genes DNA Manipulating DNA

3. The Roots of DNA Research Gregor Mendel –1860s –Pea plants –Heritable traits –Occur in pairs –Concept of chromosomes Figure 4.1a: Gregor Mendel © National Library of Medicine

4. The Roots of DNA Research Thomas Hunt Morgan –1910 –Fruit flies –Chromosomes Willard Johannsen –Genes Figure 4.1b: Thomas Hunt Morgan © National Library of Medicine

5. The Roots of DNA Research Focus on DNA –1869 Johann Fredrich Meischer White blood cells from salmon –1920s Alfred Mirsky Same DNA amount in all cells –1928 Frederick Griffith Pneumococci Transforming factor –1944 Oswald Avery DNA is transforming factor

6. The Roots of DNA Research Griffith & Avery Fig. 4.2 Transformation experiments of Griffith, A-B

7. The Roots of DNA Research Griffith & Avery Fig. 4.2 Transformation experiments of Griffith, C-D

8. The Roots of DNA Research Focus on DNA –Alfred Hershey & Barbara Chase Radiolabeled bacteriophages Determined that DNA is heritable material

9. The Roots of DNA Research: Hershey & Chase Fig 4.3 Determining the function of DNA

10. The Roots of DNA Research The structure of DNA –1920s Pheobus Levine DNA and RNA Existence of ribose and deoxyribose Existence of A, T, G, C, and U –Erwin Chargaff Amount of T equals amount of A; G equals C –1953 Rosalind Franklin, Maurice Wilkins, James Watson, Francis Crick X-ray crystallography Double helix Figure 4.4a: James D. Watson and Francis H. C. Crick in 1952 © Cold Springs Harbor Laboratory Archives/Photo Researchers, Inc.

11. DNA to Protein 20 different amino acids Over 10,000 different proteins per microbe How does this diversity occur?

12. DNA to Protein The intermediary and the genetic code –DNA in nucleus, proteins made in cytoplasm –RNA present in large quantities –RNA moves from nucleus to cytoplasm –Information transfer DNA->RNA->protein –1961 Francis Crick: codons –Determination of genetic codes for each amino acid

13. Table 4-2: The Genetic Codes for Several Amino Acids

14. DNA to Protein Transcription –Promoter –mRNA –Codons –Eukaryotic mRNA Splicing: introns and exons 7-methyl guanosine cap Poly-A tail

15. DNA to Protein: Transcription Figure 4.7: The transcription process

16. DNA to Protein Translation –On ribosomes –Amino acids come together to form proteins, based on the code in the mRNA –tRNAs facitilate by “carrying” amino acids to the ribosome –Codon-anticodon interactions –Formation of peptide bonds between amino acids –Process repeats until termination –Further protein modifications after translation

17. DNA to Protein: Translation Figure 4.9: A summary view of protein synthesis

18. DNA to Protein Gene regulation –lac operon (codes for proteins that breakdown lactose) Absence of lactose –Repressor bound to operator –No transcription –No gene expression –No energy waste, making proteins required to break down lactose Presence of lactose –Lactose bound to repressor –Repressor no longer bound to operator –Transcription –Gene expression –Only now making proteins required to break down lactose

19. DNA to Protein: Gene Regulation Figure 4.10: The operon theory of gene regulation

20. Genes and Genomics Genomics –The study of genomes –1977 Frederick Sanger DNA sequencing Exact nucleotide makeup of  X174.

21. Genes and Genomics –Effort to map the human genome –Compare E. coli (4.7 million bases) to humans (3 billion bases) –Expansion of effort Escherichia coli (bacterium) Saccharomyces cerevisiae (yeast) Caenorhabditis elegans (nematode) Drosophila melanogaster (fruitfly) Zea mays (corn) Mus musculus (mouse)

22. Genes and Genomics The methods of genome research –Traditional method Ordering genes on chromosomes Gene linkage map Physical map Base-by-base sequencing –“Shotgun” sequencing Fragment entire genome Sequence each base Reassemble entire genome from sequenced fragments

23. Genes and Genomics: Methods of genome research Figure 4.11: Sequencing methods for determining the base sequence of a molecule of DNA Traditional method

24. Genes and Genomics: Methods of genome research Figure 4.11: Sequencing methods for determining the base sequence of a molecule of DNA Shotgun method

25. Genes and Genomics Microbial genomics –1995 J. Craig Venter and Hamilton Smith Haemophilus influenzae sequence First free-living organism to be sequenced 1.8 million bases 1749 predicted genes –Mycoplasma genitalium –Methanococcus jannaschii (archaea, not bacteria) –Staphylococcus aureus –Saccharomyces cerevisiae Multiple chromosomes 12 million bases 6000 predicted genes

26. Genes and Genomics Microbial genomes –1997 Helicobacter pylori (gastric ulcers) Borrelia burgdorferi (Lyme disease) Streptococcus pneumoniae (bacterial pneumonia) Bacillus subtilis (industrial microbe) Escherichia coli (microbiological model bacterium) –1998 Treponema pallidum (syphilis) Mycobacterium tuberculosis (tuberculosis) Caenorhabditis elegans (biological model nematode) Arabidopsis thaliana (biological model mustard plant)

27. Genes and Genomics The human genome –1989: the beginning –British and American labs –2000: Draft copy of human genome Figure 4.12: President Clinton with J. Craig Venter and Francis Collins announcing the draft copy of the human genome © AP Photos

28. Genes and Genomics The human genome –Human genes number 35-50,000 (lower than 100,000 prediction) –About 3,164,700,000 bases, close to 3 billion estimate –Average gene about 3000 bases –99.9% of DNA bases are the same in most people –50% of newly discovered genes have no known function –Less than 2% of bases code for proteins –Over 50% of DNA was considered “junk” –Chromosome 1: 2968 genes (most) –Chromosome Y: 231 genes (least)