Nucleotides and Polynucleotides — AQA A-level Biology

SPEC 3.1.5 - BIOLOGICAL MOLECULES

Nucleic Acids

DNA & RNA structure, complementary base pairing, and semi-conservative DNA replication

The Monomer: Nucleotides

Both DNA and RNA are polymers of nucleotides joined by phosphodiester bonds.

Nucleotide

The monomer of nucleic acids; consists of a pentose sugar, a phosphate group, and a nitrogenous base.

Condensation Reaction

Adjacent nucleotides are joined by a condensation reaction forming a phosphodiester bond between the phosphate of one nucleotide and the sugar of the next — making the sugar-phosphate backbone.

DNA vs RNA

Both are polynucleotides, but they differ in three key ways:

FeatureDNARNA

Pentose sugarDeoxyriboseRibose

BasesAdenine, Thymine, Guanine, CytosineAdenine, Uracil, Guanine, Cytosine

StrandsDouble-strandedSingle-stranded

LengthVery longRelatively short

LocationNucleus (+ mitochondria, chloroplasts)Nucleus + cytoplasm

Examiner Alert

DNA contains thymine (T); RNA contains uracil (U). Never write "thymine" for RNA or "uracil" for DNA. This is one of the most common base errors in the exam.

DNA Double Helix Structure

DNA is a double helix — two antiparallel polynucleotide strands wound together, held by hydrogen bonds between complementary bases.

Key Rule

Antiparallel: one strand runs 5'→3', the other 3'→5'. The sugar-phosphate backbone is on the outside; bases face inward.

Complementary Base Pairing

The specific hydrogen bonding between bases: adenine pairs with thymine (A–T, 2 hydrogen bonds) and guanine pairs with cytosine (G–C, 3 hydrogen bonds) in DNA; adenine pairs with uracil (A–U) in RNA.

DNA Base Pairs

A – T (adenine–thymine): 2 hydrogen bonds

G ≡ C (guanine–cytosine): 3 hydrogen bonds

Why It Matters

High G≡C content → harder to denature (more bonds)

Chargaff's rule: %A = %T; %G = %C

Bases are complementary — not identical

Maths Tip

If %G = 22%, then %C = 22%. Therefore %A + %T = 100 − 44 = 56%, so %A = %T = 28%. Use Chargaff's rule to calculate any missing base frequency.

Phosphodiester Bonds

Phosphodiester Bond

The covalent bond formed between adjacent nucleotides in a polynucleotide chain, linking the phosphate group of one nucleotide to the pentose sugar of the next via a condensation reaction.

The result is the sugar-phosphate backbone — the structural "spine" of each strand.

Semi-Conservative Replication

The method of DNA replication in which each new DNA molecule consists of one original (template) strand and one newly synthesised strand.

Antiparallel

The two strands of a DNA double helix run in opposite directions — one 5'→3', the other 3'→5'. DNA polymerase can only synthesise in the 5'→3' direction.

Why "Semi-Conservative"?

Each daughter molecule conserves one strand from the parent molecule. Neither strand is discarded — this ensures genetic information is faithfully passed to daughter cells.

Replication: Step by Step

1

DNA helicase unwinds the double helix and breaks the hydrogen bonds between complementary bases. The two template strands are exposed.

2

Free DNA nucleotides (with complementary bases) align against each template strand by complementary base pairing (A with T; G with C).

3

DNA polymerase catalyses condensation reactions joining adjacent nucleotides, forming new phosphodiester bonds. It works in the 5'→3' direction only.

4

Result: two identical DNA molecules, each with one original strand and one newly synthesised strand — semi-conservative.

Key Enzymes in Replication

DNA Helicase

Unwinds the DNA double helix and breaks hydrogen bonds between complementary bases during replication.

DNA Polymerase

Catalyses the condensation reaction joining adjacent nucleotides to form a new polynucleotide strand. Can only work 5'→3'.

Examiner Alert

Never write "DNA unzips" — this scores no marks. The correct answer is: "hydrogen bonds between complementary bases are broken by DNA helicase." Always name the enzyme and specify the type of bond.

The Bond Rule

Hydrogen bonds hold the two strands together (broken by helicase)

Phosphodiester bonds form the sugar-phosphate backbone (made by DNA polymerase via condensation)

Meselson & Stahl, 1958

This experiment provided evidence for the semi-conservative model of DNA replication — validating the Watson-Crick model.

1

Bacteria grown in ¹⁵N (heavy nitrogen) medium — all DNA becomes heavy (both strands).

2

Bacteria transferred to ¹⁴N (light nitrogen) medium and allowed to replicate once.

3

After one replication: all DNA is intermediate density (one ¹⁵N strand + one ¹⁴N strand). ✓ Supports semi-conservative.

4

After two replications: half the DNA is intermediate, half is light. ✓ Confirms semi-conservative model.

Exam Skill

Ultracentrifugation separated DNA by density into bands. After one replication, both semi-conservative AND dispersive models predict intermediate-density DNA — so generation 1 alone cannot distinguish them. It is the two-generation result (50% intermediate + 50% light) that confirms semi-conservative: dispersive replication would produce all molecules at an even lighter intermediate density after two replications, not two discrete bands.

Replication Visualised

Result

Each daughter molecule is identical to the parent and to each other, ensuring genetic continuity between cell generations.

Antiparallel Strands & Directionality

DNA strands are antiparallel — they run in opposite directions. This is fundamental to the structure of the double helix.

5' and 3' Ends

5' end: the end with a free phosphate group

3' end: the end with a free hydroxyl (–OH) group on the pentose sugar

One strand runs 5'→3' top to bottom; the complementary strand runs 3'→5' top to bottom (i.e. 5'→3' in the opposite direction)

DNA polymerase can only add new nucleotides to the 3' end of a growing strand — so synthesis only proceeds in the 5'→3' direction

Synoptic Link — Topic 4: Transcription

The antiparallel, double-stranded nature of DNA is also critical for transcription (Lesson 4.02) — the template strand is read 3'→5' by RNA polymerase, producing mRNA in the 5'→3' direction. This uses the same principle of complementary base pairing.

The Watson-Crick Model

Watson and Crick proposed the double helix model of DNA in 1953, using X-ray crystallography data from Rosalind Franklin and Chargaff's rules.

Key Features of the Model

Two polynucleotide strands wound into a right-handed double helix

Strands are antiparallel (opposite orientations)

Bases face inward; sugar-phosphate backbone faces outward

Specific base pairing: A–T and G–C only

One full turn every 10 base pairs

Evaluation Skill

The spec says you should be able to "evaluate the work of scientists in validating the Watson-Crick model." Meselson & Stahl (1958) confirmed semi-conservative replication — this is the key experiment to know. The result only makes sense if the double helix unwinds with each strand as a template, as the model predicts.

Examiner Intelligence

Top Errors to Avoid

Error 1: Saying "DNA unzips" — no marks. Say: "hydrogen bonds broken by DNA helicase."

Error 2: Writing thymine in RNA — RNA has uracil, not thymine.

Error 3: Saying "complementary bases" without specifying which pairs which — always name the specific pairs.

Error 4: Confusing the bond types — hydrogen bonds hold strands together; phosphodiester bonds form the backbone.

Error 5: Saying DNA polymerase "breaks" or "unwinds" DNA — that is helicase's job.

Mark-Winning Language

Use: "DNA helicase breaks hydrogen bonds between complementary bases." Then: "Free DNA nucleotides align by complementary base pairing." Then: "DNA polymerase catalyses condensation reactions forming phosphodiester bonds."

DEEP Framework: Replication

How to structure a 6-mark question: "Describe the process of semi-conservative DNA replication."

DEEP CHAIN

DDefine: Semi-conservative replication produces two identical DNA molecules, each with one original and one new strand.

EExplain mechanism: DNA helicase unwinds the double helix and breaks hydrogen bonds between complementary bases; both template strands are exposed. Free DNA nucleotides align by complementary base pairing (A–T, G–C). DNA polymerase catalyses condensation reactions, joining nucleotides by phosphodiester bonds in the 5'→3' direction.

EEvidence: Meselson and Stahl (1958) used ¹⁵N/¹⁴N labelling and ultracentrifugation to show intermediate-density DNA after one replication — confirming the semi-conservative model.

PPractical/significance: Semi-conservative replication ensures genetic continuity — daughter cells inherit an exact copy of the parent genome. Errors in replication may lead to mutations.

Practice Question

Describe and explain the role of two named enzymes in the semi-conservative replication of DNA. [4 marks]

1

DNA helicase unwinds the double helix and breaks hydrogen bonds between complementary bases, separating the two template strands. (2 marks)

2

DNA polymerase catalyses condensation reactions between adjacent nucleotides, forming phosphodiester bonds to build the new polynucleotide strand in the 5'→3' direction. (2 marks)

✓

Mark scheme note: Credit requires naming the enzyme AND stating its specific action. "Joins nucleotides" without saying "condensation reaction" or "phosphodiester bond" may only score 1 mark.

Practice Question

A DNA sample contains 18% adenine bases. Calculate the percentage of guanine bases in the same sample. Show your working. [2 marks]

Step 1:

By Chargaff's rule: %A = %T = 18%

Step 2:

%A + %T = 36%; therefore %G + %C = 100 − 36 = 64%

Step 3:

%G = %C = 64 ÷ 2 = 32%

✓

Answer: 32% guanine. One mark for correct working; one mark for correct answer.

Synoptic Links

Synoptic Link — Topic 4: Gene Expression

The structure of DNA and RNA you learn here underpins transcription and translation (Lesson 4.02). During transcription, RNA polymerase uses one DNA strand as a template to build mRNA by complementary base pairing. During translation, tRNA anticodons pair with mRNA codons — again using the same base-pairing rules.

Synoptic Link — Topic 1.07: ATP

ATP is a nucleotide derivative — it shares the same basic structure as a ribonucleotide (adenine + ribose) but has three phosphate groups. Understanding nucleotide structure here makes ATP structure straightforward in the next lesson.

Cross-Topic Vocabulary

Phosphodiester bonds appear in both DNA/RNA and are also cleaved by restriction enzymes (Topic 8). Complementary base pairing is the mechanism behind hybridisation probes, PCR, and gene technology.

Summary

Core Knowledge Checklist

ConceptKey Detail

Nucleotide componentsPentose sugar + phosphate group + nitrogenous base

DNA vs RNA sugarDeoxyribose (DNA) vs ribose (RNA)

DNA base pairsA–T (2 H-bonds); G≡C (3 H-bonds)

RNA base swapUracil replaces thymine; single-stranded

Phosphodiester bondJoins adjacent nucleotides; forms backbone; made by condensation

DNA helicaseUnwinds helix; breaks hydrogen bonds

DNA polymeraseJoins nucleotides by condensation; 5'→3' only

Semi-conservativeEach daughter DNA = 1 old strand + 1 new strand

Meselson & Stahl¹⁵N/¹⁴N ultracentrifugation confirmed semi-conservative model

Top Exam Tip

Every mark-scheme answer on replication expects enzyme names and bond types. Never write "DNA unzips" — always say "DNA helicase breaks hydrogen bonds between complementary bases." Then "DNA polymerase catalyses condensation reactions forming phosphodiester bonds."