The Discovery and Structure of DNA as the Genetic Material

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DNA as the Genetic Material

The Search for the Genetic Material

Early in the 20th century, scientists debated whether DNA or protein was the hereditary material. Proteins, with their structural diversity, were initially favored. However, experiments with bacteria and viruses provided crucial evidence that DNA is the molecule of inheritance.

Evidence That DNA Can Transform Bacteria

Frederick Griffith's 1928 experiment with Streptococcus pneumoniae demonstrated the phenomenon of transformation. He found that nonpathogenic bacteria could become pathogenic when mixed with heat-killed pathogenic bacteria, suggesting that a 'transforming principle' was responsible for transferring genetic information.

Transformation: A change in genotype and phenotype due to the assimilation of external DNA by a cell.
Pathogenic (S) strain: Has a capsule, causes disease.
Nonpathogenic (R) strain: Lacks a capsule, does not cause disease.

Griffith's experiment: injection of S and R strains into mice Results of Griffith's experiment: mouse health outcomes

Conclusion: The R strain was transformed into the S strain by an unknown heritable substance from the dead S cells, later identified as DNA.

Evidence That Viral DNA Can Program Cells

Bacteriophages (phages) are viruses that infect bacteria. The Hershey-Chase experiment (1952) used radioactive labeling to show that DNA, not protein, is the genetic material injected by phages into bacteria, directing the production of new viruses.

Bacteriophage structure: Composed of DNA (or RNA) and a protein coat.
Key finding: Only DNA enters the bacterial cell and directs viral replication.

Bacteriophage structure and infection of a bacterial cell Hershey-Chase experiment: tracing DNA and protein with radioisotopes

Conclusion: DNA is the hereditary material in phages, as only labeled DNA was found inside infected cells and passed on to progeny phages.

The Structure of DNA

DNA Composition and Chargaff's Rules

DNA is a polymer of nucleotides, each consisting of a nitrogenous base, a deoxyribose sugar, and a phosphate group. Erwin Chargaff discovered that DNA composition varies between species and that the amount of adenine (A) equals thymine (T), while guanine (G) equals cytosine (C).

Nucleotide structure: Base (A, T, G, C), deoxyribose sugar, phosphate group.
Chargaff's rules: %A = %T and %G = %C in any DNA sample.

Structure of a DNA nucleotide and backbone Comparison of DNA and RNA nucleotide structure

Example: In sea urchin DNA, A = 32.8%, T = 32.1%, G = 17.7%, C = 17.3%.

Source of DNA	Adenine	Guanine	Cytosine	Thymine
Sea urchin	32.8	17.7	17.3	32.1
Salmon	29.7	20.8	20.4	29.1
Wheat	28.1	21.8	22.7	?
E. coli	24.7	26.0	?	?
Human	30.4	?	?	30.1
Ox	29.0	?	?	?
Average %

Table of DNA base composition in various species

Application: Chargaff's rules allow prediction of base composition in unknown DNA samples.

Building the Structural Model of DNA

X-ray Crystallography and the Double Helix

Rosalind Franklin's X-ray diffraction images revealed that DNA is helical, with a uniform diameter and repeating structure. Watson and Crick used these data, along with Chargaff's rules, to build a double helix model with antiparallel sugar-phosphate backbones and specific base pairing.

Antiparallel strands: The two DNA strands run in opposite directions (5' to 3' and 3' to 5').
Double helix: Two strands twisted around each other, with bases paired in the interior.

$Rosalind Franklin and her X-ray diffraction photo of DNA$ Visual representations of DNA structure

Base Pairing and the Uniformity of the Double Helix

The double helix has a uniform diameter because a purine (A or G, two rings) always pairs with a pyrimidine (T or C, one ring). This pairing is stabilized by hydrogen bonds: A pairs with T (two hydrogen bonds), and G pairs with C (three hydrogen bonds).

Pyrimidines: Cytosine (C), Thymine (T) – single ring
Purines: Adenine (A), Guanine (G) – double ring
Base pairing: A–T and G–C

Base pairing and helix width: purine-purine, pyrimidine-pyrimidine, purine-pyrimidine Hydrogen bonding between base pairs in DNA

Key Point: The sequence of bases along a DNA strand encodes genetic information, while the base-pairing rules ensure accurate replication and transmission of genetic material.

Summary Table: Key Discoveries in DNA as Genetic Material

Scientist(s)	Experiment	Key Finding
Griffith	Transformation in S. pneumoniae	Heritable substance (DNA) can transform bacteria
Hershey & Chase	Phage infection of E. coli	DNA, not protein, is the genetic material
Chargaff	Base composition analysis	%A = %T, %G = %C; DNA composition varies by species
Franklin	X-ray diffraction	DNA is a double helix with regular structure
Watson & Crick	Model building	Double helix structure explains replication and heredity

Conclusion

The discovery of DNA as the genetic material and the elucidation of its double helix structure were foundational to modern biology. These advances explained how genetic information is stored, replicated, and transmitted, setting the stage for molecular genetics and biotechnology.