Science 240

Paradigms in molecular biology

Lectures #28 & #29

Monday, 9 November 1998 and Wednesday, 11 November 1998

1. Physicists become biologists
   1. Shared features of Drosophila and maize as study organisms for geneticists
   2. Shift to use of bacteria and bacteriophage
      1. Emphasis on simplicity
      2. Identify the "atoms" of heredity
2. The molecular paradigm
   1. DNA is the hereditary material
   2. Genetic information is stored in the linear sequence of nucleotides of which DNA is composed (triplets)
   3. Information flows from DNA through RNA to protein: the "Central Dogma of Molecular Biology"
   4. Study of genotype and phenotype replaced by study of DNA and protein
3. Jumping genes in bacteria
   1. Escherichia coli: mutations have several unexpected effects
      1. Abolish the function of the target gene, but also reduce expression of those "downstream"
      2. Capable of spontaneous reversion, but did not respond to known mutagenic agents
      3. Soon discovered that these mutations were caused by insertion of small pieces of DNA. Reversion was caused by excision.
      4. Excision sometimes picks up a piece of the bacterial chromosome and moves it to a new place.
   2. Salmonella typhimurium: drug-resistance genes move freely from plasmid to chromosome to phage in all possible combinations
4. A Kuhnian revolution?
   1. Was there a crisis in Mendelian or in molecular genetics?
   2. Does Kuhn's incommensurability thesis account for McClintock's inability to communicate her results to her colleagues?
   3. Is genetics today simply different from Mendelian genetics of the 1930's, or does it actually provide a more accurate description of hereditary phenomena.
5. To reduce or not to reduce
   1. Molecular geneticists focus on simple systems because they are the easiest to understand and to relate to physics and chemistry
      1. Tremendous advances in understanding chemical basis of heredity
      2. Bacteria and bacteriophage do not develop
      3. Phenomena found in complex, multicellular organisms: are they worthy of study
   2. McClintock provided rigorous formal description of phenomena, but provided no mechanistic explanation
   3. Supervenience
      1. Two systems that have identical properties at a lower hiearchical level, e.g., chemical, will also have identical properties at a higher hierarchical level, e.g., heredity.
      2. Two systems with identical (or very similar) properties at a higher hierarchical level need not have identical properties at a lower hierarchical level.