AIFSET

• The work of Mendel and others who followed him gave us an idea of inheritance patterns. However the nature of those 'factors' which determine the phenotype was not very clear.
• The entire body of molecular biology was a consequent development with major contributions from Watson, Crick, Nirenberg, Khorana, Kornbergs (father and son), Benzer, Monod, Brenner, etc.
• A parallel problem being tackled was the mechanism of evolution. Awareness in the areas of molecular genetics, structural biology and bio informatics have enriched our understanding of the molecular basis of evolution.
• James Dewey Watson


  Born in Chicago on 6 April 1928. Received B.Sc. degree in Zoology in 1947. Received Ph.D. degree in 1950 on a study of the effect of hard X-rays on bacteriophage multiplication.
• James Watson and Francis Crick

  They discovered their common interest in solving the DNA structure
• Their first serious effort was unsatisfactory. Their second effort based upon more experimental evidence and better appreciation of the nucleic acid literature, resulted, early in March 1953, in the proposal of the complementary double-helical configuration.
• Francis Harry Compton Crick


  Born on 8 June 1916, at Northampton, England. Studied physics at University College, London and obtained a B.Sc. in 1937. Completed Ph.D. in 1954 on a thesis entitled "X-ray Diffraction: Polypeptides and Proteins".
• Crick's friendship with J. D. Watson


  Led in 1953 to the proposal of the double-helical structure for DNA and the replication scheme
• Crick was made an F.R.S. in 1959.
• Honours to Watson with Crick


  • The John Collins Warren Prize of the Massachusetts General Hospital, in 1959
  • The Lasker Award, in 1960
  • The Research Corporation Prize, in 1962
  • The Nobel Prize in 1962
• Humans knew from as early as 8000-1000 B.C. that one of the causes of variation was hidden in sexual reproduction.
• DNA is a long polymer of deoxyribonucleotides
• Gregor Mendel


  Conducted hybridisation experiments on garden peas for seven years (1856-1863) and proposed the laws of inheritance in living organisms.
• Length of DNA


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


  • Bacteriophage φ×174 has 5386 nucleotides
  • Bacteriophage lambda has 48502 base pairs
  • Escherichia coli has 4.6 × 10^6 bp
  • Haploid content of human DNA is 3.3 × 10^9 bp
• During Mendel's investigations into inheritance patterns it was for the first time that statistical analysis and mathematical logic were applied to problems in biology.
• Polynucleotide chain


  Has three components - a nitrogenous base, a pentose sugar, and a phosphate group
• Mendel investigated characters in the garden pea plant that were manifested as two opposing traits, e.g., tall or dwarf plants, yellow or green seeds.

  
• Nitrogenous bases

  • Purines (Adenine and Guanine)
  • Pyrimidines (Cytosine, Uracil and Thymine)
• Mendel conducted artificial pollination/cross pollination experiments using several true-breeding pea lines.
• 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 OH of 5' C
• Contrasting traits selected by Mendel in pea plants


  • Smooth or wrinkled seeds
  • Yellow or green seeds
  • Inflated (full) or constricted green or yellow pods
  • Tall or dwarf plants

  
• Polynucleotide chain


  Nucleotides linked through 3'-5' phosphodiester linkage
• Mendel's hybridisation experiment to study the inheritance of one gene


  1. Crossed tall and dwarf pea plants

  2. Collected the seeds produced and grew them to generate plants of the first hybrid generation (F1)

  3. Self-pollinated the tall F1 plants to generate the Filial2 (F2) generation
• 5'-end


  Free phosphate moiety at 5'-end of sugar
• In the F1 generation, all the progeny plants were tall, like one of its parents; none were dwarf.
• In the F2 generation, some of the offspring were 'dwarf'; the proportion of plants that were dwarf were 1/4th of the plants while 3/4th of the plants were tall.
• Genes


  The units of inheritance that contain the information required to express a particular trait in an organism
• 3'-end


  Free OH of 3'C group
• Alleles


  Slightly different forms of the same gene that code for a pair of contrasting traits
• 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
• Genotype


  The genetic makeup of an organism
• DNA


  An acidic substance present in 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
• Phenotype


  The observable physical or biochemical characteristics of an organism
• Double Helix structure of DNA


  • Made of two polynucleotide chains
  • Backbone is constituted by sugar-phosphate, and the bases project inside
  • The two chains have anti-parallel polarity
  • Bases in two strands are paired through hydrogen bonds forming base pairs
  • Adenine forms two hydrogen bonds with Thymine, and Guanine is bonded with Cytosine with three H-bonds
  • The two chains are coiled in a right-handed fashion
  • The plane of one base pair stacks over the other in double helix

  
• Francis Crick proposed the Central dogma in molecular biology, which states that the genetic information flows from DNA→RNA→Protein
• Dominant


  A trait that is expressed in the phenotype of a heterozygous organism
• In some viruses the flow of information is in reverse direction, from RNA to DNA