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4
The DNA Story
Germs, Genes, and Genomics
Heredity
• Genes
• DNA
• Manipulating DNA
The Roots of DNA Research
• Gregor Mendel
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1860s
Pea plants
Heritable traits
Occur in pairs
Concept of chromosomes
Figure 4.1a: Gregor Mendel
© National Library of Medicine
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
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
The Roots of DNA
Research
Griffith & Avery
Fig. 4.2 Transformation
experiments of Griffith, A-B
The Roots of
DNA Research
Griffith & Avery
Fig. 4.2 Transformation experiments
of Griffith, C-D
The Roots of DNA Research
• Focus on DNA
– Alfred Hershey & Barbara Chase
• Radiolabeled bacteriophages
• Determined that DNA is heritable material
The Roots of DNA Research: Hershey & Chase
Fig 4.3 Determining the function of DNA
• 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
© Cold Springs Harbor Laboratory Archives/Photo Researchers, Inc.
The Roots of DNA Research
• X-ray crystallography
• Double helix
Figure 4.4a: James D. Watson
and Francis H. C. Crick in 1952
DNA to Protein
• 20 different amino acids
• Over 10,000 different proteins per microbe
• How does this diversity occur?
DNA to Protein
• The intermediary and the genetic code
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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
Table 4-2: The Genetic Codes for
Several Amino Acids
DNA to Protein
• Transcription
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Promoter
mRNA
Codons
Eukaryotic mRNA
• Splicing: introns and exons
• 7-methyl guanosine cap
• Poly-A tail
DNA to Protein: Transcription
Figure 4.7: The transcription process
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
DNA to Protein: Translation
Figure 4.9: A summary view of protein synthesis
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
DNA to Protein: Gene Regulation
Figure 4.10: The operon theory of gene regulation
Genes and Genomics
• Genomics
– The study of genomes
– 1977 Frederick Sanger
• DNA sequencing
• Exact nucleotide makeup of FX174.
Genes and Genomics
– Effort to map the human genome
– Compare E. coli (4.7 million bases) to humans (3 billion bases)
– Expansion of effort
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Escherichia coli (bacterium)
Saccharomyces cerevisiae (yeast)
Caenorhabditis elegans (nematode)
Drosophila melanogaster (fruitfly)
Zea mays (corn)
Mus musculus (mouse)
Genes and Genomics
• The methods of genome research
– Traditional method
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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
Genes and Genomics:
Methods of genome research
Figure 4.11: Sequencing methods for
determining the base sequence of a molecule
of DNA
Traditional method
Genes and Genomics:
Methods of genome
research
Figure 4.11: Sequencing methods for
determining the base sequence of a
molecule of DNA
Shotgun method
Genes and Genomics
• Microbial genomics
– 1995 J. Craig Venter and Hamilton Smith
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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
Genes and Genomics
• Microbial genomes
– 1997
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Helicobacter pylori (gastric ulcers)
Borrelia burgdorferi (Lyme disease)
Streptococcus pneumoniae (bacterial pneumonia)
Bacillus subtilis (industrial microbe)
Escherichia coli (microbiological model bacterium)
– 1998
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Treponema pallidum (syphilis)
Mycobacterium tuberculosis (tuberculosis)
Caenorhabditis elegans (biological model nematode)
Arabidopsis thaliana (biological model mustard plant)
Genes and Genomics
• The human genome
– 1989: the beginning
– British and American labs
– 2000: Draft copy of human genome
© AP Photos
Figure 4.12: President Clinton with
J. Craig Venter and Francis Collins
announcing the draft copy of the
human genome
Genes and Genomics
• The human genome
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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)