The DNA Story Germs, Genes, and Genomics 4
Dec 14, 2015
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
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
• Focus on DNA– Alfred Hershey & Barbara Chase
• Radiolabeled bacteriophages
• Determined that DNA is heritable material
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 helixFigure 4.4a: James D. Watson and Francis H. C. Crick in 1952
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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– 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
DNA to Protein
• Transcription– Promoter– mRNA– Codons– Eukaryotic mRNA
• Splicing: introns and exons
• 7-methyl guanosine cap
• Poly-A tail
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
• 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
Genes and Genomics
• Genomics– The study of genomes– 1977 Frederick Sanger
• DNA sequencing
• Exact nucleotide makeup of X174.
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)
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
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
• 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
• 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)
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
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)