The search for the genetic material: DNA is the genetic material

Griffith's transformation experiment (1928)

Griffith used two strains of the bacterium Streptococcus pneumoniae. The **S strain** forms **smooth, shiny colonies** because of a polysaccharide coat (capsule). The **R strain** forms **rough colonies** and has no coat.

1. 1
   Live S strain injected into mice → mice die of pneumonia. S is virulent.
2. 2
   Live R strain injected → mice live.
3. 3
   Heat-killed S strain injected → mice live.
4. 4★
   Heat-killed S + live R injected → mice die, and living S bacteria are recovered from them.
5. 5
   Conclusion: some 'transforming principle' passed from the dead S bacteria and changed R into S. This change was genetic, but its chemical nature was not known.

★ key step

Avery, MacLeod and McCarty: naming the transforming principle

These workers purified the proteins, DNA and RNA of heat-killed S bacteria. Only DNA changed R bacteria into S. Proteases (protein-digesting enzymes) and RNases did not stop the change, but DNase (DNA-digesting enzyme) did. So the transforming principle was DNA. Not all biologists were convinced, so firmer proof was needed.

Hershey and Chase: the blender experiment (1952)

**Bacteriophages** are viruses that infect bacteria. A phage is made of DNA inside a protein coat.

1. 1
   Some phages were grown on a medium with radioactive phosphorus (³²P). This labels DNA, because protein has no phosphorus.
2. 2
   Other phages were grown with radioactive sulphur (³⁵S). This labels protein, because DNA has no sulphur.
3. 3
   Each kind of phage was allowed to infect E. coli bacteria.
4. 4
   Blending: the mixture was shaken in a blender to strip the phage coats off the bacteria.
5. 5
   Centrifugation: the heavier bacteria settled as a pellet; the lighter phage coats stayed in the liquid (supernatant).
6. 6★
   Result: with ³²P, the bacteria were radioactive; with ³⁵S, the radioactivity was in the supernatant, not the bacteria. So DNA, not protein, entered the bacteria: DNA is the genetic material.

★ key step

DNA vs RNA as the genetic material

Both can carry genetic information: in some viruses, such as tobacco mosaic virus and Qβ bacteriophage, RNA is the genetic material.

The RNA world

RNA was the first genetic material. Key life processes, such as metabolism, translation and splicing, evolved around RNA. Early RNA acted both as the genetic material and as a catalyst; some reactions in cells are still catalysed by RNA. But a reactive catalyst is unstable as a store of information. So DNA evolved from RNA, with chemical changes that made it more stable. Its double helix and complementary strands also allow it to resist change and be repaired.