DNA

AQA spec ref: 3.4.1 - DNA, genes and chromosomes

DNA (deoxyribonucleic acid) is the molecule that carries genetic information in all living organisms. It encodes the instructions for building and operating every cell and organism - a molecule that determines development, inheritance, and evolution. Understanding DNA structure is fundamental to everything else in biology: replication, transcription, translation, mutation, and inheritance all depend on it.

The Nucleotide

DNA is a polynucleotide - a polymer built from repeating units called nucleotides. Each DNA nucleotide has three components:

1. Deoxyribose sugar - a pentose (5-carbon) sugar. The "deoxy" means it lacks one oxygen compared to ribose (the sugar in RNA). Carbon atoms in deoxyribose are numbered 1' to 5'.
2. Phosphate group - attached to the 5' carbon of the deoxyribose.
3. Nitrogenous base - one of four types, attached to the 1' carbon:

• Purines (double ring): Adenine (A) and Guanine (G)
• Pyrimidines (single ring): Thymine (T) and Cytosine (C)

Nucleotides are joined together by phosphodiester bonds, formed between the 3' carbon (hydroxyl group) of one nucleotide's deoxyribose and the 5' phosphate of the next nucleotide. This is a condensation reaction, releasing water. The resulting backbone is the sugar-phosphate backbone, with bases projecting inward.

The chain has a directionality: the 5' end (free phosphate) and the 3' end (free hydroxyl). This matters enormously - all polymerases read and synthesise DNA in specific directions relative to this polarity.

The Double Helix

DNA exists as a double-stranded helix - the famous structure elucidated by Watson and Crick in 1953, building on X-ray crystallography data from Franklin and Wilkins, and Chargaff's rules.

Key structural features:

• The two strands run antiparallel - one runs 5'→3' from top to bottom, the other runs 3'→5' from top to bottom (or equivalently, 5'→3' from bottom to top). This antiparallel arrangement is essential for replication and transcription.

• The strands are held together by hydrogen bonds between complementary base pairs:
• Adenine - Thymine (A=T): 2 hydrogen bonds
• Guanine≡Cytosine (G≡C): 3 hydrogen bonds

This is complementary base pairing (also called Chargaff's rules: A pairs with T, G pairs with C). The specificity of base pairing - the exact complementarity between A and T, and G and C - is what allows precise replication and transcription.

• G≡C has 3 hydrogen bonds, A=T has only 2. This means DNA with a higher G+C content is more thermally stable (harder to separate the two strands). This is relevant to PCR and to why different organisms' DNA has different melting temperatures.

• The helix is right-handed. The double helix makes a complete turn every ~10 base pairs.

• The two strands are further stabilised by hydrophobic stacking interactions between adjacent base pairs (the flat bases stack on top of each other like a pile of coins, with hydrophobic faces directed inward). This contributes significantly to DNA stability.

Chargaff's Rules

Before the structure was known, Erwin Chargaff measured the base composition of DNA from many species and found:

• %A always equals %T
• %G always equals %C
• But %A+T/%G+C varies between species

This was explained by Watson and Crick's double helix: A always pairs with T and G always pairs with C, which forces %A = %T and %G = %C. The ratio %A+T/%G+C varies between species because it reflects the organism's specific genetic sequence.

RNA Structure

RNA (ribonucleic acid) is also a polynucleotide but differs from DNA in three key ways:

Types of RNA:

• mRNA (messenger RNA) - carries the genetic code from DNA in the nucleus to the ribosome for translation. Produced during transcription. Has a start codon (AUG) and stop codon. Processed from pre-mRNA by removal of introns.
• tRNA (transfer RNA) - brings amino acids to the ribosome during translation. Has an anticodon (complementary to the mRNA codon) and an amino acid attachment site. Cloverleaf secondary structure.
• rRNA (ribosomal RNA) - structural and catalytic component of ribosomes. rRNA constitutes 60% of the ribosome by mass. The large ribosomal subunit's rRNA has peptidyl transferase activity (it catalyses peptide bond formation), making ribosomes ribozymes.

DNA in Eukaryotes vs Prokaryotes

Eukaryotic DNA:

• Found in the nucleus, wrapped around histone proteins
• Nucleosome: DNA wound around 8 histones (2 each of H2A, H2B, H3, H4) forming a bead-like structure
• Nucleosomes fold further into chromatin fibres - heterochromatin (tightly coiled, inactive) or euchromatin (loosely coiled, active)
• Linear chromosomes - multiple per cell (46 in humans)
• Contains introns (non-coding sequences within genes) and large amounts of non-coding DNA between genes
• Also contains mitochondrial and chloroplast DNA (small, circular) - evidence for endosymbiotic theory

Prokaryotic DNA:

• A single, circular chromosome in the cytoplasm (no nuclear envelope)
• Not associated with histones (though some histone-like proteins exist in archaea)
• Supercoiled to fit in the cell
• Contains few or no introns - genes are mostly continuous
• May also contain plasmids - small, circular, double-stranded DNA molecules separate from the main chromosome. Plasmids can carry antibiotic resistance genes and can be transferred between bacteria (conjugation), contributing to the spread of antibiotic resistance.
• Much smaller genome than eukaryotes

The Watson-Crick Discovery

Watson and Crick proposed the double helix model in 1953 (published in Nature, April 1953). Their model depended on:

• X-ray crystallography from Franklin and Wilkins showing the helical structure and spacing of the molecule
• Chargaff's rules (A=T, G=C) suggesting the pairing rules
• Knowledge of chemical bonds to determine how the bases could pair

The model immediately suggested the mechanism of replication: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."

Summary

• DNA=double-stranded antiparallel helix of polynucleotides
• Backbone: deoxyribose+phosphate (joined by phosphodiester bonds via 3'→5' linkages)
• Bases: A pairs with T (2 H-bonds), G pairs with C (3 H-bonds)
• Higher G+C content=more stable DNA
• RNA differs: ribose sugar, uracil instead of thymine, usually single-stranded
• Types of RNA: mRNA (code), tRNA (brings amino acids), rRNA (ribosome structure/catalysis)
• Eukaryotic DNA: linear, histone-bound, in nucleus, with introns
• Prokaryotic DNA: circular, no histones, cytoplasmic, no introns, plus plasmids

AQA Exam Tips

• Phosphodiester bonds: formed between the 3' -OH of one nucleotide's deoxyribose and the 5' phosphate of the next. The word "phosphodiester" is a mark-scheme term - use it.
• Antiparallel: always state that the two strands run in opposite 5'→3' directions. This is why DNA polymerase can only synthesise in the 5'→3' direction, leading to leading and lagging strand synthesis.
• A=T, G≡C: two H-bonds and three H-bonds respectively. AQA commonly asks how many hydrogen bonds. Never say A pairs with G or T with C.
• RNA differences from DNA: deoxyribose vs ribose; thymine vs uracil; double vs single strand. State all three.
• Plasmids: small, circular DNA. Used in genetic engineering (see DNA replication and Protein synthesis). Carry antibiotic resistance genes - clinically relevant to the spread of antimicrobial resistance.
• Nucleosome = DNA + histones: when asked to describe chromosome structure, start here. 8 histones + DNA wound around them = 1 nucleosome. Nucleosomes coil further into chromatin.
• G+C content and stability: more G≡C pairs (3 H-bonds) → more energy needed to separate strands → higher melting temperature. This is the basis of PCR primer design.