The molecule basis of Inheritance

1) The search for genetic material lead to DNA

Until 1940s, the great heterogeneity and specificity of function of proteins seemed to indicate that proteins were the genetic material. Then, T.H. Morgan showed that genes are located on chromosomes, the two constituents of chromosomes - proteins and DNA - were the candidates for the genetic material. However, it was not consistent with experiments with microorganisms like bacteria and viruses.T.H. Morgan arrived with this idea through the comparison of fruit flies' phenotypes and research done by Mendel.

The discovery of genetic role of DNA began with research by Frederick Griffth in 1928. He studied Treptococcus pnewmoniae, a bacterium that is responsible for pneumonia in mammals.In an experiment, he mixed heat-killed Smooth strain (harmful) with live Rough (harmless) strain bacteria and injected into a mouse. Logically, the mouse should live because harmful bacteria is removed and harmless bacteria is injected; however, the mouse is dead due to phenotype and genotype change due to the assimilation of a foreign substance (DNA). This phenomenon is called transformation.

Living S cells are found in blood sample from dead mouse after injected by heat-killed S cells mixed with living R cells.

Hershey and Chase did experiment on T2 Phage, a virus.  DNA and protein were stained respectively, and DNA of virus was confirmed to be found inside infected cell, not protein. A virus infects a host cell and takes over the cell's metabolic machinery to replicate itself. Viruses are not considered organisms.

By 1847, Erwin Chargaff had developed a seres of rules based on a survey of DNA composition in organisms. DNA consists of nitrogenous base, deoxyribose, and a phosphate group. The base could be adenine (A), thymine (T), guanine (G), or cytosine (C). Chargaff noted that DNA composition varies from species to species. 

Chargaff's rules: (%T=%A) & (%G=%C)

2) Watson and cRick discovered the double helix by building models to conform to X-ray data

Maurice Wilkins and Rosalind Franklin used X-ray crystallography to study the structure of DNA. X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and diffracts into many specific directions. The diffraction pattern can be used to deduce the three-dimensional shape of molecules.Franklin did not receive proper recognition because she was female and was dead from cancer (overdose of X-Ray).

James Watson and Francis Crick learned from Franklin's study that DNA was helical in shape and he deduced the width of the helix and the spacing of bases. The nitrogenous bases are paired in specific combiantions: A and T & G and C. A and G are purine and C and T are pyrimidine. A purine-purine pair would be too wide and a pyrimidine-pyrimidine paring would be too narrow. Thus, Watson and Crick came up with a pyrimidine-purine paring which is consistent with X-ray data.There are minor groups and major groups in DNA.  Minor are shorter connections between bases, whereas major have longer connections between bases. Hydrogen bonds connected two strands together.  Adenine and thymine would only form double bonds, and guanine and cytosine would only form triple bonds. This explained Chargaff's rules. Watson and Crick began to work on a model of DNA with two strands, the double helix. The linear sequence of the four bases can be varied in countless ways.