The search for the genetic material

What carries the plan?

A pea plant gives its seeds the factors for height and colour. Mendel showed that. But what is a factor made of? Until the 1940s, most scientists guessed a protein. A protein is built from 20 kinds of amino acids, so it can be put together in a huge number of ways. DNA looked too plain. It has only four kinds of bases.

The DNA itself had been known since 1869. Friedrich Miescher found an acidic substance in the nucleus and called it nuclein. Three experiments, one after the other, showed that this plain molecule is the genetic material.

Griffith and the transforming principle (1928)

Frederick Griffith studied Streptococcus pneumoniae, the bacterium that causes pneumonia. It grows in two forms.

• The S strain makes smooth, shiny colonies. Each cell has a capsule, a coat of polysaccharide. This strain is virulent, which means that it causes disease and kills mice.
• The R strain makes rough colonies. It has no capsule. It is not virulent.

Griffith injected mice in four ways.

The last result is the surprise. Dead S cells cannot kill a mouse, and R cells cannot kill a mouse either. Yet together they did. Something passed from the dead S cells into the living R cells and changed them into S cells with a capsule. Griffith called it the transforming principle. The change was heritable. The new S cells kept their capsule when they divided.

Griffith did not know what the transforming principle was. Heat killed the S cells but did not destroy it.

Avery, MacLeod and McCarty (1933 to 1944)

Three scientists, Oswald Avery, Colin MacLeod and Maclyn McCarty, set out to find the molecule. They broke open heat-killed S cells and separated the proteins, the RNA, the DNA and the other molecules. Only the extract with DNA could transform R cells.

Then they used enzymes, which are proteins that digest one kind of molecule.

• Protease digests proteins. The extract still transformed R cells.
• RNase digests RNA. The extract still transformed R cells.
• DNase digests DNA. The extract could no longer transform R cells.

So the transforming principle is neither a protein nor RNA. It is DNA. Some scientists doubted the result. They said that a trace of protein might still be at work. One more experiment was needed.

You should find that the S colonies fall only when the DNA is destroyed. The other two sliders change nothing.

Hershey and Chase (1952)

Alfred Hershey and Martha Chase used a bacteriophage, a virus that infects bacteria. A phage is a simple thing. It has a protein coat and DNA inside. When it infects a bacterium, it makes more phages inside the cell.

They needed a way to tell the protein from the DNA. Look at the two molecules.

• DNA has phosphorus, and no sulphur.
• Protein has sulphur (in the amino acids cysteine and methionine). The protein coat of the phage has no phosphorus.

So radioactive phosphorus, 32P, tags the DNA. Radioactive sulphur, 35S, tags the protein. They grew one batch of phages with 32P and another with 35S. Carbon, hydrogen, nitrogen and oxygen would not do, because both molecules have them.

1. Each batch of phages infected Escherichia coli.
2. The mixture was spun in a blender. This shook the empty phage coats off the surface of the bacteria.
3. A centrifuge spun the mixture. The heavy bacteria went to the bottom as a pellet. The light coats stayed in the liquid, the supernatant.

The bacteria made new phages. So the DNA, and not the protein, carried the instructions. This settled the question for most scientists.

What does a genetic material need?

A genetic material must have four properties.

1. It must copy itself (replicate).
2. It must be stable, in chemistry and in structure.
3. It must allow slow changes, which are mutations. Evolution needs them.
4. It must be able to express itself as characters, such as the characters that Mendel followed.

RNA can do some of this. It can carry a message. It can also act as a catalyst, and then it is called a ribozyme. Some viruses, such as the tobacco mosaic virus, have RNA as their genetic material. But DNA is the genetic material of most living things, because it is more stable.

Thymine has a methyl group, and this also adds to the stability of DNA. NCERT also describes the RNA world. It is the idea that RNA came first, as the genetic material and as a catalyst, and that DNA evolved later from it, because DNA is more stable.

Try it in Python

The program works out what share of the label is in the pellet for two tubes.

Practise with new numbers

Common mistakes

• Saying that Griffith proved that DNA is the genetic material. He found only that something passes from dead S cells to living R cells.
• Saying that the dead S cells came back to life. The living R cells were changed into S cells.
• Mixing up the labels. Phosphorus is in DNA. Sulphur is in protein.
• Saying that the phage protein entered the bacterium. The 35S stayed in the supernatant.
• Saying that protease destroys the transforming principle. It does not. DNase does.

Remember these

• Griffith (1928): Streptococcus pneumoniae, S (capsule, virulent) and R (no capsule). Heat-killed S plus live R killed the mouse. Transforming principle.
• Avery, MacLeod and McCarty: protease and RNase did not stop the transformation. DNase did. So it is DNA.
• Hershey and Chase (1952): 32P for DNA, 35S for protein. Blender and centrifuge. The 32P was in the bacteria.
• A genetic material copies itself, is stable, allows slow mutation and expresses itself. RNA is less stable than DNA, because of the 2′ OH.

Check yourself

Try each one on your own first. If you are stuck, open a hint. Then check with Show the answer.

1. In Griffith's last experiment the mouse died. Why did it die, although both kinds of cell, alone, were harmless?

2. Avery, MacLeod and McCarty added three enzymes to the extract of S cells. Which one stopped the transformation, and what does that show?

3. Why did Hershey and Chase use 32P for the DNA and 35S for the protein, and not radioactive carbon for both?

4. In which part of the tube did they find the 32P, and what does that show?

5. Give two reasons why DNA is a better genetic material than RNA.

References

• NCERT (2023). Biology, Textbook for Class XII, chapter 5, Molecular Basis of Inheritance.
• Clark M. A. et al. (2018). Biology 2e, OpenStax, chapter 14, section 14.1, Historical Basis of Modern Understanding.
• Hershey A. D. and Chase M. (1952). Independent functions of viral protein and nucleic acid in growth of bacteriophage. Journal of General Physiology, 36, 39 to 56.