When Friedrich Miescher in 1869 discovered a new, acidic, phosphorus-containing substance made up of very large molecules, which he named “nuclein,”its biological role was not apparent. The term “nucleic acid,”later to be recognized as deoxyribonucleic acid (DNA),was introduced by Richard Altmann in 1889. By 1900,the purine and pyrimidine bases were known, and twenty years later, the two kinds of nucleic acid,RNA and DNA,were distinguished. An incidental but precise observation in1928 and further investigations in 1944 indicated that DNA could be the carrier of genetic information.
DNA as a Carrier of Genetic Information
A. Griffith’s observation
In 1928,the English microbiologist Fred Griffith made a remarkable observation. While investigating various strains of Pneumococcus bacteria (Streptomyces pneumoniae ,a cause of inflammation of the lungs,pneumonia),he determined that mice injected with strain S (smooth) died (1 ).On the other hand, animals injected with strain R (rough)survived (2 ).When he inactivated the lethal S strain by heat, the animals also survived (3). Surprisingly, a mixture of the nonlethal R strain and the heatinactivated S strain had the same lethal effect as the original S
strain (4 ).When he found normal living pneumococci of the S strain in the animals’ blood,he concluded that cells of the R strain
must have changed into cells of the S strain. This is called bacterial transformation.For some time,this surprising result could not be explained and was met with skepticism.Its relevance for genetics was not apparent.
B. The transforming principle is DNA
Griffith’s findings formed the basis for investigations by Avery,MacLeod,and McCarty (1944)at the Rockefeller Institute in New York.
They determined that the chemical basis of the transforming principle was DNA. From cultures of an S strain (1 )they produced an extract of lysed cells (cell-free extract,2 ).After all its proteins, lipids, and polysaccharides had been removed,the extract still retained the ability to transform pneumococci of the R strain to pneumococci of the S strain (transforming principle,3 ).
With further studies,Avery and co-workers determined that this was due to the DNA alone.
Thus,the DNA must contain the corresponding genetic information, which explained Griffith’s observation.Heat had left the DNA of the bacterial chromosomes intact.The section of the chromosome with the gene responsible for capsule formation (S gene)could be released from the destroyed S cells and taken up by some R cells in subsequent cultures.After the S gene was incorporated into its DNA,an R cell was transformed into an S cell (4 ).This observation
is based on the ability of bacteria to take up foreign DNA,which alters (transforms)some of their genetic attributes correspondingly.
C. Genetic information is transmitted by DNA only
The final evidence that DNA, and no other molecule, transmits genetic information was provided by Hershey and Chase in 1952. They labeled the capsular protein of bacteriophages with radioactive sulfur (35 S)and the DNA with radioactive phosphorus (32 P).When bacteria were infected with the labeled bacteriophage, only 32 P (DNA)entered the cells, and not the 35 S (capsular protein).The subsequent formation of new,complete phage particles in the cell proved that DNA was the exclusive carrier of the genetic information needed to form new phage particles,including their capsular protein .