Molecular basis of inheritance

• DNA

  Deoxyribonucleic acid - the genetic material in most organisms
• RNA


  Ribonucleic acid - acts as genetic material in some viruses, and has other roles as messenger, adapter, structural and catalytic molecule
• In the previous chapter, you have learnt the inheritance patterns and the genetic basis of such patterns
• At the time of Mendel, the nature of those 'factors' regulating the pattern of inheritance was not clear
• Over the next hundred years, the nature of the putative genetic material was investigated culminating in the realisation that DNA is the genetic material, at least for the majority of organisms
• Nucleotide

  The monomer unit of nucleic acids (DNA and RNA), consisting of a nitrogenous base, a pentose sugar, and a phosphate group
• Polynucleotide chain


  A long polymer of nucleotides
• Purines


  Nitrogenous bases (Adenine and Guanine)
• Pyrimidines

  Nitrogenous bases (Cytosine, Uracil and Thymine)
• Nucleoside

  A nitrogenous base linked to a pentose sugar
• Nucleotide

  A nucleoside with a phosphate group attached
• Phosphodiester linkage


  The covalent bond that links the phosphate group of one nucleotide to the sugar of the next, forming the backbone of a polynucleotide chain
• 5' end


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

  The end of a polynucleotide chain with a free hydroxyl group
• Complementary base pairing

  The pairing of adenine with thymine, and guanine with cytosine, in a DNA double helix
• Double helix structure of DNA

  • Made of two polynucleotide chains
  • Chains have anti-parallel polarity
  • Bases paired through hydrogen bonds
  • Coiled in a right-handed fashion
  • Uniform distance between the two strands
• The proposition of a double helix structure for DNA and its simplicity in explaining the genetic implication became revolutionary
• Central dogma


  The flow of genetic information from DNA to RNA to protein
• In some viruses the flow of information is in reverse direction, that is, from RNA to DNA
• Nucleoid


  The region in a prokaryotic cell where the DNA is located, not enclosed within a nuclear membrane
• Histones

  Positively charged, basic proteins that DNA is wrapped around to form nucleosomes
• Nucleosome


  The basic unit of chromatin, consisting of DNA wrapped around a histone octamer
• Chromatin


  The complex of DNA and proteins that makes up the contents of the cell nucleus
• Euchromatin


  Loosely packed, transcriptionally active chromatin
• Heterochromatin

  Densely packed, transcriptionally inactive chromatin
• Frederick Griffith's experiments with Streptococcus pneumoniae demonstrated the 'transforming principle' that could convert non-virulent bacteria into virulent ones
• Oswald Avery, Colin MacLeod and Maclyn McCarty determined that the 'transforming principle' was DNA
• Alfred Hershey and Martha Chase's experiments with bacteriophages provided unequivocal proof that DNA is the genetic material
• Viruses grown in the presence of radioactive phosphorus contained radioactive DNA but not radioactive 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 unequivocal proof that DNA is the genetic material came from the experiments of Alfred Hershey and Martha Chase (1952). They worked with viruses that infect bacteria called bacteriophages.
• Hershey-Chase experiment

  1. Bacteriophage attaches to bacteria

  2. Viral genetic material enters bacterial cell

  3. Bacterial cell treats viral genetic material as its own

  4. Bacterial cell manufactures more virus particles
• Hershey and Chase worked to discover whether it was protein or DNA from the viruses that entered the bacteria.
• Hershey-Chase experiment

  1. Grow viruses on medium with radioactive phosphorus

  2. Grow viruses on medium with radioactive sulfur

  3. Radioactive phages allowed to attach to E. coli bacteria

  4. Viral coats removed from bacteria by blending

  5. Virus particles separated from bacteria by centrifugation
• Bacteria infected with viruses that had radioactive DNA were radioactive, indicating that DNA was the material that passed from the virus to the bacteria. 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.
• In some viruses, RNA is the genetic material (for example, Tobacco Mosaic viruses, QB bacteriophage, etc.).
• 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'
• Because of rule of base pairing and complementarity, both the nucleic acids (DNA and RNA) have the ability to direct their duplications.
• The genetic material should be stable enough not to change with different stages of life cycle, age or with change in physiology of the organism.