DNA Structure: The Watson and Crick Model (HSC SSCE Biology): Revision Notes

DNA structure: The Watson and Crick model

Introduction

Today we understand that cells store their biological information in a molecule called DNA (deoxyribonucleic acid). However, the actual chemical nature and structure of this hereditary material remained a mystery until the middle of the 20th century. The discovery of DNA's structure revolutionised our understanding of genetics and heredity.

A brief history of DNA discovery

Early discoveries (1869-1944)

The journey to understanding DNA began over 150 years ago:

1869 - Friedrich Miescher: A Swiss scientist discovered a chemical he called 'nuclein' in the nuclei of cells. This substance turned out to be DNA mixed with proteins. Miescher was the first scientist to identify DNA as a distinct molecule.

1910 - Discovery of chromosomes: Scientists discovered that chromosomes were made of a mixture of DNA and protein, and that they carried units of heredity called genes (a term coined by William Johannsen in 1909).

1930s-1940s: Most scientists expected that proteins would hold the secret of heredity because they are built from 20 different amino acids, compared to DNA's four bases. However, some researchers began to suspect DNA was the key.

1944 - Oswald Avery: Working with his team at Rockefeller University hospital in New York, Avery provided the first experimental proof that DNA, not protein, carries genetic information. Many biologists remained sceptical, suspecting his DNA samples might have been contaminated with protein.

The race to discover DNA's structure (1951-1953)

By 1951, several research teams were competing to solve the puzzle of DNA's structure:

British teams:

• James Watson and Francis Crick worked at the Cavendish laboratory, Cambridge University, under Lawrence Bragg's leadership
• Maurice Wilkins and Rosalind Franklin worked at King's College, London, under John Randall's leadership

American team:

• Linus Pauling led research in the United States

There was intense rivalry between these groups. Lawrence Bragg and Linus Pauling (who had won a Nobel Prize for his work on chemical bonds) had a longstanding competitive relationship.

In early 1953, Linus Pauling proposed that DNA was the heredity molecule with a triple helix structure. However, this model proved to be incorrect.

The breakthrough announcement

Watson and Crick used chemical evidence and X-ray crystallography data to construct their model of DNA's molecular structure. Their model revealed a stable molecule that could store vast amounts of information. They described DNA as a two-stranded molecule with paired bases twisted into a spiral ladder, which they called a 'double helix'.

A critical feature of their model was that it could explain how the molecule could copy itself (self-replicate).

On 28 February 1953, Watson and Crick won the race and announced at a pub called The Eagle that they had discovered 'the secret of life'.

Collaborative scientific work

Watson and Crick worked collaboratively, evaluating the research and conclusions of other scientists. They asked questions of colleagues like Maurice Wilkins, who showed Watson one of Rosalind Franklin's X-ray crystallography photographs of DNA (unfortunately without first asking her permission).

They applied critical and creative thinking to analyse primary and secondary chemistry and crystallography data. By considering the quality of all available evidence and using careful reasoning, they built and rigorously tested their model. Their innovation, attention to scientific detail, and collaborative approach led to a valid conclusion that won them the Nobel Prize in 1962.

The Watson and Crick model of DNA structure

The double helix

Watson and Crick's model showed DNA as a large linear molecule arranged as a double helix or 'twisted ladder'. The key features of this structure are:

• Four nitrogenous bases held in pairs by hydrogen bonds
• The genetic information is stored in the sequence or order of these bases
• Two strands that run parallel to each other but in opposite directions (antiparallel)

Key structural features

The antiparallel arrangement:

Crick realised that each DNA strand, made of a sugar-phosphate backbone, runs antiparallel to the other. This means the twisting strands run parallel but in opposite directions. X-ray crystallography showed a set distance between the 'backbones' of the molecule.

The ladder structure:

Think of DNA as a twisted ladder:

• The vertical sides are made of alternating sugar (deoxyribose) and phosphate molecules, forming a sugar-phosphate backbone
• The rungs are pairs of nitrogenous bases that line up between the backbones
• Each base has one end attached to the backbone and the other end hydrogen-bonded to another base

Nucleotide pairing and bonding

Complementary base pairing:

Watson and Crick discovered that to keep the DNA backbones at equal distances from each other, a double-ringed purine base must bond with a single-ringed pyrimidine base:

• Adenine (A) pairs with thymine (T) - forms two hydrogen bonds
• Guanine (G) pairs with cytosine (C) - forms three hydrogen bonds

This is called complementary base pairing.

Base classification:

• Purines (larger, double-ringed): adenine (A) and guanine (G)
• Pyrimidines (smaller, single-ringed): cytosine (C) and thymine (T)

Evidence for base pairing:

Watson and Crick found support for this pairing in Chargaff's rule. In 1951, Austrian biochemist Erwin Chargaff discovered that in DNA, the ratio of A

and C is always 1:1.

DNA serves as a template for replication

Watson and Crick's model explained how DNA meets all requirements of hereditary material:

1. Information storage: DNA can carry all the instructions for cell formation and function in coded form, using sequences of just four nitrogenous bases

2. Self-replication: The structure allows DNA to copy itself. Each strand serves as a template for enzymes to build a new complementary strand

3. Inheritance: DNA can be transferred from one generation to the next, packaged as chromosomes and carried by gametes (sex cells)

Validation of the Watson and Crick model

Watson and Crick's findings were supported by multiple lines of evidence:

Finding	Evidence-based reasoning
The whole DNA 'ladder' molecule spirals and is known as the 'double helix'	Evidence: X-ray crystallography suggested a helix measuring $3.4$ nm for every turn. This fitted the model where exactly 10 base pairs would measure $3.4$ nm in length and make up one twist of the helix
The four nitrogenous bases (A, G, C, T) always pair as A–T and C–G	Evidence: Chargaff's rule stated that DNA has a 1:1 ratio of pyrimidine and purine bases. Specifically, the amount of guanine equals cytosine and the amount of adenine equals thymine. Watson and Crick found that complementary base pairing (A–T and G–C) was essential to keep the DNA backbones equidistant
The two complementary strands are held together by hydrogen bonds between the bases	Reasoning: Chemically, when A bonds to T, a double hydrogen bond forms. When G bonds to C, a triple hydrogen bond forms
The strands of the backbone are identical and run in opposite directions (antiparallel)	Evidence: DNA crystal images generated by Rosalind Franklin looked the same when turned upside down or backwards. Reasoning: The backbones are made of sugar-phosphate molecules, based on the ratio of these components in chemical analyses
Each DNA strand serves as a template for producing a complementary strand, allowing self-replication	Reasoning: The two complementary strands could 'unzip' if the hydrogen bonds break between base pairs, allowing them to replicate

Model building approach:

Watson and Crick built physical models to test how atoms fit together. They sometimes used cardboard cut-outs to represent the four nitrogenous bases and other DNA components, arranging them like a jigsaw puzzle on a desk. They initially made errors in the configuration of thymine and guanine rings. Based on a suggestion from American scientist Jerry Donahue, they adjusted the atomic arrangements and found the perfect fit: complementary base pairing with the correct ratios to reflect Chargaff's rule and hydrogen bonding between purines and pyrimidines.

The structure of nucleic acids

Components of a nucleotide

All nucleic acids are polymers (long chains) made up of simple repeating units called nucleotides. Each nucleotide consists of three parts:

1. A phosphate group
2. A sugar (deoxyribose in DNA, ribose in RNA)
3. A nitrogenous base attached to the sugar

Nucleotides link together to form single chains (as in RNA) or double strands (as in DNA).

DNA strand length

DNA strands can be extremely long. For example, human chromosome 1 contains 249 million base pairs of DNA, representing approximately 8% of the total DNA in a human cell.

DNA packaging with histones

DNA is packaged efficiently in chromosomes with the help of proteins called histones. DNA coils around these proteins, similar to how cotton thread winds around a cotton reel. This packaging:

• Keeps long DNA threads compact
• Makes DNA easier to sort and separate during cell division
• Allows efficient transport of genetic material between generations
• May play a role in exposing sections of DNA so genes can be expressed

The genetic code

The genetic code is created by the consecutive sequence of bases along the DNA strand. These base sequences differ in each gene, providing the unique 'genetic code' for cells to build specific proteins.

Comparing DNA and RNA

While DNA and RNA are both nucleic acids made of nucleotides, they have distinct roles and characteristics:

DNA (deoxyribonucleic acid):

• Stores genetic information that controls the cell and organism
• Main chemical component of chromatin in the nucleus
• Small amounts also found in mitochondria and chloroplasts
• Transmits inherited information during cell division and reproduction
• Contains the base thymine (T)
• Forms a double-stranded double helix

RNA (ribonucleic acid):

• Found in small amounts in the nucleus and larger amounts in the cytoplasm
• Usually associated with ribosomes
• Contains the base uracil (U) instead of thymine (T)
• Forms single strands
• Three main types with different functions:
  • Messenger RNA (mRNA): carries information from DNA to the cytoplasm
  • Ribosomal RNA (rRNA): associated with proteins in ribosomes
  • Transfer RNA (tRNA): assists in translating the mRNA message into proteins

Remember!