Today, it is widely known that DNA is the genetic material. However, the identification of the molecules of inheritance came as a major challenge for biologists in the 20th Century.
Thomas H Morgan and his group showed that genes are located along chromosomes. Therefore the two chemical components of the chromosome-DNA and protein- became the two probable choices of the molecules of inheritance. However, proteins were a much stronger choice than DNA during this time because they were discovered as macromolecules of great diversity and specificity of function. These two requirements were considered essential for the genetic material. This view, however, changed as experiments with organisms gave unexpected results. The role of DNA was first worked out by bacteria and the viruses that infect them.
Evidence that DNA can Transform Bacteria
We can trace the first experiment pertaining to the journey of trying to find the genetic material back to 1928. Fredrick Griffith was trying to develop a vaccine against pneumonia using a bacterium (streptococcus pneumonia) that caused pneumonia in mammals. There were two strains (varieties) of this bacterium, one pathogenic (smooth) and nonpathogenic (rough). When he killed the pathogenic strain with heat and put the remains with the living nonpathogenic strain, some of the living cells became pathogenic. This newly acquired trait also was inherited by the offspring. This led Griffith to conclude that some chemical component of the dead pathogenic cell caused this heritable change. He called this phenomenon Transformation. Oswald Avery and his colleagues were American Bacteriologists that were trying to find this mysterious chemical component. The three candidates they focused on were DNA, RNA, and proteins. Only when DNA was allowed to remain active in the nonpathogenic bacteria did transformation occur.
Evidence that Viral DNA can Program Cells
Viruses that infect bacteria are called Bacteriophages. Alfred Hershey and Martha Chase performed experiments are proved that DNA was the genetic material of T2, which was a bacteriophage. T2 was composed almost entirely of DNA and Protein. Scientists knew at this time that T2 could reprogram its host cell to produce viruses, but they didn’t know which chemical component- DNA or Protein- was responsible. They devised an experiment to show that only of these two components enters the components of T2. Viruses (T2 bacteriophage) were grown in one of two isotopic mediums in order to radioactively label a specific viral component. Viruses grown in radioactive sulfur had radiolabeled proteins (sulfur is present in proteins but not DNA). Viruses grown in radioactive phosphorus had radiolabeled DNA (phosphorus is present in DNA but not proteins). The bacteria were found to be radioactive when infected by the radiolabeled DNA viruses but were not radioactive when infected by the radiolabeled protein viruses. This demonstrated that DNA was the genetic material because DNA was transferred to the Bacteria. The Hershey and Chase experiment created a landmark study because it provided evidence that DNA was the hereditary material, at least for viruses.
Additional Evidence that DNA is the genetic material
More evidence that DNA is the genetic material came from the biochemist Erwin Chargaff. Chargaff analyzed the base composition of DNA from a different number of organisms and concluded that the base composition of DNA varied from one species of organism to another. This evidence of molecular diversity showed that DNA was a more credible candidate for the genetic material. He also developed what we call “Chargaff’s Rule.” It states that there is an approximately equal ratio of Adenine and Thymines and there is an approximately equal ratio of Cytosine and Guanine.
Building the Structural Model of DNA
Now that DNA was found to be the genetic material, there was still controversy over the structure of DNA. Linus Pauling, a scientist at the California Institute of Technology, concluded that DNA was three-stranded. However, two scientists named James Watson and Francis Crick concluded differently. They analyzed an X-Ray diffraction photo of DNA that Rosalind Franklin had compiled. While looking at the photo, they concluded that DNA was helical in shape and that it was double-stranded. Pertaining to the chemistry of the DNA molecule, Rosalind Franklin concluded that the sugar-phosphate backbone of DNA was on the outside of the double helix. This makes sense because it put the relatively hydrophobic nucleotide bases in the interior of the molecule and away from the surrounding aqueous solution. They also concluded that only a purine and pyrimidine could hydrogen bond because the size was a perfect fit for the double-strand model. In shorthand, A pairs with T, and G pairs with C. The diversity of DNA comes from the fact that the linear sequence of the four bases can be varied in countless ways, and each gene has a unique order or base sequence.