Meischer collected pus filled hospital bandages and from them he isolated and purified nuclei. On chemical fractionation he found that a cellular chemical content had a very high component of phosphorous compound than what was known before.
As the new compound was obtained from nucleus, Miescher named it nuclein. Subsequently nuclein was isolated from many sources and due to its acidic properties, it was named nucleic acid. Up to 1952 however, interest in nuclei acids was limited to only its physiochemical studies.
When its role in inheritance was proved nucleic acid became the focus of intensive research. Comparative studies of nucleic acids and proteins revealed that while proteins are of diverse types, there are only two types of nucleic acids.
It was hard to believe that nucleic acids which apparently had no diversity could be the basis of heredity and not the proteins.
Presently however, there is not even an iota of doubt as to the fact that nucleic acids alone constitute the hereditary factor. Three major experiments helped provide an evidence for this.
1. Bacterial transformation:
Fred Griffith and English bacteriologist worked with Diplococcus Pneumococci and found out that there are two strains in this – Virulent and Virulent.
When injected to experimental mice the virulent strains cause the death of the mice while a virulent strains do not cause any harm.
Griffith showed ‘hat heat killed virulent strains injected into the mice along with a virulent strains cause the death of the mice and from the body of the mice live virulent strains can be obtained.
Dawson and Sia (1931) showed that the heat killed virulent strains can transform a virulent strains on a nutrient broth.
Alloway (1933) showed that even a lysed cell of virulent strain retains the ability of transformation thereby indicating that some component of the cell rather than the entire cell was involved in transformation.
2. Nature of the transforming agent:
Three scientists – O.T. Avery, Colin Macleod and Maclyn McCarty (1944) went into serious search of the transforming agent from the lysed cells of bacteria. Even after digestion of polysaccharide coat, the cell retained the ability of transformation.
This shows that the capsule has no role in transformation. Similarly protein degradation also had no adverse effect on transformation.
With the two important components out of the way, it thus became clear that nucleic acids perhaps might play a role in transformation. It was shown that the DNA fraction of nucleic acids was responsible for transformation.
It was also shown that if the cells are treated with DNAse (a DNA degrading enzyme), the transforming ability will be lost. Enzymes which digest RNA do not disturb transformation.
3. Bacteriophages and chemical basis of heredity:
Bacteriophages are viruses that attack a bacterial cell and multiply inside the (bacterial) cell. The phage attaches itself to the bacterial cell and injects its components into the cell where replica of phages are produced.
Hershey and Chase (1952) conducted an experiment to find out which component of the bacteriophage carries the genetic information necessary for the replication of viruses.
They cultured the host bacterium Escherichia coli in’ a medium containing radio isotopes of Sulphur (S35) and phosphorus (P32). When T2 phages attacked these cells subsequently, the labelled compounds get incorporated in phage DNA which always has radioactive phosphorus but not any sulphur.
In the next set of experiment only the protein coat of T2 phage was labeled with S35 and the DNA core of another was labeled with P32.
Hershey and Chase separated the radioactive phages by centrifugation and allowed them to infect a population of non radioactive bacteria.
A few minutes after initial infection they separated the phages from bacteria by agitating the medium. After centrifugation the host and the parasite were separated by centrifugation and their radioactivity measured.
About 95% of P32 was found in bacteria while about 95% S35 was seen in phages. This experiment conclusively proved that during infection only DNA is injected into the medium.
This is the reason why the non radioactive bacteria showed labeled P32 (as they obtained it from labelled phage DNA). For this work Hershey was awarded Nobel Prize in 1969.
Thus the experiments of Hersehy and Chase Avery, Mcleod and McCarty Griffith etc., clearly proved that DNA constitutes the chemical basis of Heredity.
4. TMV and chemical basis of heredity:
The discovery that DNA is the hereditary material posed some problems to explain the inheritance in instances such as TMV (Tobacco mosaic virus) where there is no DNA (TMV is a RNA virus).
But the absence of DNA has not prevented TMV from transmitting its characters from one generation to the other. TMV is made up of a RNA core and a helical protein coat. The protein RNA component of TMV can be easily separated by shaking the viral particles in a mixture of water and phenol.
Frankek Conrad and Wichams (1955) separated the protein and RNA from TMV and reassembled the particles from the individual components thus indicating the purification process (of the components) does not affect their function.
Subsequently Gierr and Shramm (1956) showed that on contact with the host only the RNA can bring about the disease and not the protein coat. In TMV therefore it is RNA which is the hereditary material.
It can therefore be concluded that nucleic acids in general and DNA in particular is the hereditary material in most of the organisms and in the absence of DNA (as in some viruses) RNA can constitute the genetic material.
5. Nucleic acids:
These are the most important constituents of the nucleus playing a vital role in the inheritence of characters from one generation to the other. There are two types of nucleic acids – Deoxyribose nucleic acid (DNA) and Ribose nucleic acid (RNA).
While both constitute the genetic material in different organisms, it is predominantly the DNA which is the genetic material in most of the organisms. The following are some of the important milestones in the discovery of Nucleic acids.
1. Meischer( 1869) isolated nucleic acids and called them nuclein.
2. Hertwig (1884) suggested a hereditary role to the nuclein
3. Kossel (18 84) recognized purines and pyrimidines in the nucleic acids.
4. Feulgen (1912) devised basic fushsin dye positive only to DNA.
5. Astbury and Bell (1938) showed that the bases in DNA molecule are arranged one above the other.
6. Avery, Macleod and Macarty (1944) presented evidence for DNA to be the genetic material.
7. Chargaff (1950) showed that DNA contains equal amount of purines and pyrimidines.
8. Wilkins etal( 1950) identified the molecular distance between the bases.
9. Furberg (1952); DNA is a coil of single chain.
10. Pauling and Corey (1952); DNA is a helix of three chains.
11. Watson and Crick (1953) demonstrated the double helix model for DNA molecule.
12. Meselson and Stahl (1958) demonstrated the semi conservative replication in DNA.
13. Jacob and Monod (1961) postulated the presence of RNA in protein synthesis.