DNA as the Genetic Material: Historical Experiments and Molecular Structure

DNA as the Genetic Material

Historical Search for the Genetic Material

The identification of DNA as the hereditary material was a pivotal moment in biology. Early 20th-century scientists debated whether proteins or DNA carried genetic information, as proteins were known for their complexity and diversity, while DNA was thought to be too simple. This view changed through a series of landmark experiments.

Griffith's Transformation Experiment

Frederick Griffith's 1928 experiment with Streptococcus pneumoniae provided the first evidence that a "transforming principle" could transfer genetic traits between bacteria.

• S strain (smooth): Pathogenic, has a protective capsule.

• R strain (rough): Nonpathogenic, lacks a capsule.

• When heat-killed S cells were mixed with living R cells and injected into mice, the mice died, and living S cells were recovered from their blood.

• This indicated that some heritable substance from the dead S cells transformed the R cells into pathogenic S cells.

Evidence from Bacteriophages: The Hershey-Chase Experiment

Further evidence came from studies of bacteriophages (viruses that infect bacteria). Hershey and Chase (1952) used radioactive labeling to show that DNA, not protein, is the genetic material that viruses inject into bacteria to program viral replication.

• Phages consist of DNA enclosed in a protein coat.

• Radioactive sulfur labeled proteins; radioactive phosphorus labeled DNA.

• Only radioactive DNA entered bacterial cells and directed the production of new phages.

Molecular 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 two key rules:

• Base composition varies between species.

• In any species, the amount of adenine (A) equals thymine (T), and the amount of guanine (G) equals cytosine (C).

Table: Base Composition in Different Species

This table demonstrates Chargaff's rules by showing the base percentages in DNA from various organisms.

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	?	?	?

Discovery of the Double Helix

The three-dimensional structure of DNA was elucidated by James Watson and Francis Crick, aided by Rosalind Franklin's X-ray diffraction images. The structure is a double helix with two antiparallel sugar-phosphate backbones and nitrogenous bases paired in the interior.

• X-ray diffraction revealed the helical structure and regular spacing of bases.

• Antiparallel strands: The two DNA strands run in opposite directions (5' to 3' and 3' to 5').

• Base pairing: Adenine pairs with thymine (A-T) via two hydrogen bonds; guanine pairs with cytosine (G-C) via three hydrogen bonds.

Summary Table: Key Features of DNA Structure

Feature	Description
Polymer type	Polynucleotide
Backbone	Sugar-phosphate, covalently bonded
Strand orientation	Antiparallel (5' to 3' and 3' to 5')
Base pairing	A-T (2 H-bonds), G-C (3 H-bonds)
Helix	Right-handed double helix

Significance of the Double Helix Model

The double helix structure explained how DNA could store genetic information and be faithfully replicated. The sequence of bases encodes genetic instructions, and complementary base pairing enables accurate copying during cell division.

Key Terms

• Transformation: Uptake of external DNA by a cell, resulting in a change in genotype and phenotype.

• Bacteriophage (phage): A virus that infects bacteria.

• Nucleotide: The building block of DNA, consisting of a phosphate group, deoxyribose sugar, and nitrogenous base.

• Antiparallel: Refers to the opposite orientation of the two DNA strands.

• Double helix: The spiral structure formed by two complementary strands of DNA.

Key Equations

• Base pairing: $[A] = [T]$ and $[G] = [C]$

• Total base percentage: $[A] + [T] + [G] + [C] = 100\%$