Molecular basis of inheritance

• DNA is a long polymer of deoxyribonucleotides
• Length of DNA


  Number of nucleotides (or base pairs) present in it
• Length of DNA in different organisms

  • Bacteriophage φ×174: 5386 nucleotides
  • Bacteriophage lambda: 48502 base pairs
  • Escherichia coli: 4.6 × 10^6 base pairs
  • Human haploid DNA: 3.3 × 10^9 base pairs
• Nucleotide


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


  • Purines: Adenine, Guanine
  • Pyrimidines: Cytosine, Uracil, Thymine
• Nucleoside


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


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


  Nucleotides linked through 3'-5' phosphodiester linkages
• 5' end


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


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


  • Made of two polynucleotide chains with anti-parallel polarity
  • Bases paired through hydrogen bonds (A-T, G-C)
  • Coiled in a right-handed fashion with a pitch of 3.4 nm and ~10 base pairs per turn
  • Plane of one base pair stacks over the other for stability
• The length of DNA double helix in a typical mammalian cell is approximately 2.2 metres
• Nucleoid


  Region in prokaryotes where the DNA is held with some proteins
• Nucleosome


  DNA wrapped around a histone octamer, the basic repeating unit of chromatin
• Chromatin


  Thread-like stained bodies in the nucleus, consisting of nucleosomes
• Euchromatin


  Loosely packed, transcriptionally active chromatin
• Heterochromatin


  Densely packed, transcriptionally inactive chromatin
• The biochemical nature of the genetic material was not clear until the experiments of Griffith, Avery-MacLeod-McCarty, and Hershey-Chase
• Transforming principle


  A substance from heat-killed S strain bacteria that could transform R strain bacteria into the virulent S form
• Avery-MacLeod-McCarty showed that the transforming principle was DNA, not protein or RNA
• Hershey-Chase showed that it is the DNA, not the protein, from bacteriophages that enters the bacterial cell and is the genetic material
• Griffith's 'transforming principle' experiments showed that heat, which killed the bacteria, at least did not destroy some of the properties of the genetic material
• DNA


  More stable chemically and structurally compared to RNA
• RNA


  2'-OH group makes it labile and easily degradable, also known to be catalytic and reactive
• DNA is a better genetic material compared to RNA
• Presence of thymine at the place of uracil confers additional stability to DNA
• RNA mutates at a faster rate compared to DNA
• RNA can directly code for the synthesis of proteins, while DNA is dependent on RNA for protein synthesis
• RNA was the first genetic material, but DNA evolved from RNA to be more stable
• Watson and Crick proposed the semiconservative model of DNA replication
• Meselson and Stahl's experiment to prove semiconservative DNA replication

  1. Grew E. coli in 15N medium, then transferred to 14N medium and extracted DNA samples at different time intervals

  2. Separated DNA samples using CsCl density gradient centrifugation
• DNA-dependent DNA polymerase


  • Highly efficient enzyme that catalyzes DNA replication at a very high rate (around 2000 base pairs per second)
  • Catalyzes the reaction with a high degree of accuracy to avoid mutations
• DNA replication requires additional enzymes besides DNA polymerase, like DNA ligase
• DNA replication initiates at specific origin of replication regions
• Transcription


  The process of copying genetic information from one strand of DNA into RNA
• Transcription unit


  Defined by a promoter, structural gene, and terminator in DNA
• Only one strand of DNA is transcribed, not both strands
• A double stranded RNA would prevent RNA from being translated into protein and the exercise of transcription would become a futile one.
• Transcription Unit


  Defined primarily by three regions in the DNA: (i) A Promoter, (ii) The Structural gene, (iii) A Terminator