MOLECULAR INHERITANCE

• DNA is a long polymer of deoxyribonucleotides
• Nucleotide


  Has three components - a nitrogenous base, a pentose sugar (ribose in case of RNA, and deoxyribose for DNA), and a phosphate group
• Nitrogenous bases


  • Purines (Adenine and Guanine)
  • Pyrimidines (Cytosine, Uracil and Thymine)
• Nucleoside


  A nitrogenous base linked to the OH of 1' C pentose sugar through a N-glycosidic linkage
• Nucleotide


  A nucleoside with a phosphate group linked to the OH of 5' C through phosphoester linkage
• Polynucleotide chain


  Two nucleotides linked through 3'-5' phosphodiester linkage
• 5'-end


  The end of a polynucleotide chain with a free phosphate moiety
• 3'-end


  The end of a polynucleotide chain with a free OH of 3'C group
• In RNA, every nucleotide residue has an additional -OH group present at 2'-position in the ribose, and uracil is found at the place of thymine
• DNA


  An acidic substance present in the nucleus, first identified by Friedrich Meischer in 1869
• In 1953, James Watson and Francis Crick proposed the Double Helix model for the structure of DNA based on X-ray diffraction data

  
• Double Helix structure of DNA

  • Made of two polynucleotide chains
  • The two chains have anti-parallel polarity
  • The bases in two strands are paired through hydrogen bonds forming base pairs
  • The two chains are coiled in a right-handed fashion
  • The plane of one base pair stacks over the other in double helix

  
• The proposition of a double helix structure for DNA and its simplicity in explaining the genetic implication became revolutionary

  
• Central dogma


  The genetic information flows from DNA → RNA → Protein
• In some viruses the flow of information is in reverse direction, that is, from RNA to DNA
• Nucleosome


  The negatively charged DNA is wrapped around the positively charged histone octamer
• Chromatin


  The repeating unit of nucleosomes in the nucleus
• Euchromatin


  Loosely packed chromatin that is transcriptionally active
• Heterochromatin


  Densely packed chromatin that is transcriptionally inactive
• Transforming Principle


  1. Heat-killed S strain bacteria transformed R strain bacteria to become virulent

  2. The 'transforming principle' transferred from the heat-killed S strain enabled the R strain to synthesise a smooth polysaccharide coat
• Oswald Avery, Colin MacLeod and Maclyn McCarty discovered that DNA alone from S bacteria caused R bacteria to become transformed
• Alfred Hershey and Martha Chase proved that it was DNA from viruses that entered bacteria, not protein
• Inhibit transformation, suggesting that the DNA caused the transformation. They concluded that DNA is the hereditary material, but not all biologists were convinced.
• The Genetic Material is DNA


  The unequivocal proof that DNA is the genetic material came from the experiments of Alfred Hershey and Martha Chase (1952)
• Hershey-Chase experiment


  1. Viruses grown in the presence of radioactive phosphorus contained radioactive DNA but not radioactive protein

  2. Viruses grown on radioactive sulfur contained radioactive protein but not radioactive DNA

  3. Bacteria infected with viruses that had radioactive DNA were radioactive, indicating that DNA was the material that passed from the virus to the bacteria

  4. Bacteria infected with viruses that had radioactive proteins were not radioactive, indicating that proteins did not enter the bacteria from the viruses
• DNA is the genetic material that is passed from virus to bacteria
• Properties of Genetic Material (DNA versus RNA)


  DNA is the predominant genetic material, whereas RNA performs dynamic functions of messenger and adapter
• Criteria for a molecule to act as genetic material

  • It should be able to generate its replica (Replication)
  • It should be stable chemically and structurally
  • It should provide the scope for slow changes (mutation) that are required for evolution
  • It should be able to express itself in the form of 'Mendelian Characters'
• Both DNA and RNA have the ability to direct their duplications
• Stability of genetic material


  DNA is chemically less reactive and structurally more stable when compared to RNA
• The presence of thymine at the place of uracil also confers additional stability to DNA
• RNA being unstable, mutate at a faster rate. Consequently, viruses having RNA genome and having shorter life span mutate and evolve faster.
• RNA can directly code for the synthesis of proteins, hence can easily express the characters. DNA, however, is dependent on RNA for synthesis of proteins.
• DNA being more stable is preferred for storage of genetic information. For the transmission of genetic information, RNA is better.
• RNA World


  RNA was the first genetic material. RNA used to act as a genetic material as well as a catalyst, but RNA being a catalyst was reactive and hence unstable. Therefore, DNA has evolved from RNA with chemical modifications that make it more stable.
• Watson and Crick had immediately proposed a scheme for replication of DNA, termed as semiconservative DNA replication.
• Meselson and Stahl's Experiment


  1. Grew E. coli in a medium containing 15NH4Cl, then transferred to a medium with normal 14NH4Cl and took samples at various time intervals

  2. The DNA extracted from the culture one generation after the transfer had a hybrid or intermediate density

  3. DNA extracted from the culture after another generation was composed of equal amounts of this hybrid DNA and of 'light' DNA
• The experiments proved that the DNA in chromosomes also replicate semiconservatively.
• DNA-dependent DNA polymerase


  The main enzyme that uses a DNA template to catalyse the polymerisation of deoxynucleotides
• DNA-dependent DNA polymerases catalyse polymerisation only in one direction, that is 5'→3'.