Nucleic acids and protein synthesis

• One idea runs through the whole topic: complementary base pairing copies DNA, makes mRNA and matches each tRNA to its codon. Keep track of the 5′ and 3′ ends, because every new strand, of DNA or RNA, is made 5′ → 3′.
• Antiparallel; A–T two, C–G three. Every new strand grows 5′ → 3′, so one is lagging. mRNA is complementary to the template and matches the non-transcribed strand.

• 6.1.1 I can describe — describe the structure of nucleotides, including the phosphorylated nucleotide ATP (structural formulae are not expected)
• 6.1.2 I can state — state that the bases adenine and guanine are purines with a double ring structure, and that the bases cytosine, thymine and uracil are pyrimidines with a single ring structure (structural formulae for bases are not expected)
• 6.1.3 I can describe — describe the structure of a DNA molecule as a double helix, including: • the importance of complementary base pairing between the 5′ to 3′ strand and the 3′ to 5′ strand (antiparallel strands) • differences in hydrogen bonding between C–G and A–T base pairs • linking of nucleotides by phosphodiester bonds
• 6.1.4 I can describe — describe the semi-conservative replication of DNA during the S phase of the cell cycle, including: • the roles of DNA polymerase and DNA ligase (knowledge of other enzymes in DNA replication in cells and different types of DNA polymerase is not expected) • the differences between leading strand and lagging strand replication as a consequence of DNA polymerase adding nucleotides only in a 5′ to 3′ direction
• 6.1.5 I can describe — describe the structure of an RNA molecule, using the example of messenger RNA (mRNA)
• 6.2.1 I can state — state that a polypeptide is coded for by a gene and that a gene is a sequence of nucleotides that forms part of a DNA molecule
• 6.2.2 I can describe — describe the principle of the universal genetic code in which different triplets of DNA bases either code for specific amino acids or correspond to start and stop codons
• 6.2.3 I can describe — describe how the information in DNA is used during transcription and translation to construct polypeptides, including the roles of: • RNA polymerase • messenger RNA (mRNA) • codons • transfer RNA (tRNA) • anticodons • ribosomes
• 6.2.4 I can state — state that the strand of a DNA molecule that is used in transcription is called the transcribed or template strand and that the other strand is called the non-transcribed strand
• 6.2.5 I can explain — explain that, in eukaryotes, the RNA molecule formed following transcription (primary transcript) is modified by the removal of non-coding sequences (introns) and the joining together of coding sequences (exons) to form mRNA
• 6.2.6 I can state — state that a gene mutation is a change in the sequence of base pairs in a DNA molecule that may result in an altered polypeptide
• 6.2.7 I can explain — explain that a gene mutation is a result of substitution or deletion or insertion of nucleotides in DNA and outline how each of these types of mutation may affect the polypeptide produced

Precise vocabulary is part of the biology. Water moves down a water potential gradient; an active site is complementary to its substrate; enzymes are denatured, not killed; ATP releases energy when it is hydrolysed, and no process in a cell produces energy. Give a calculated answer to the same number of significant figures as the least precise data, or one more, with its unit. A fifth of the qualification is experimental: Papers 3 and 5 test AO3 only, and their questions may be set in contexts outside the syllabus content, so the practical work in this chapter is set out as variables, method, recording, graphs and evaluation rather than as theory.

• “The mRNA has the same base sequence as the template strand.” Correct mRNA is complementary to the template strand, not a copy of it. Its sequence is the same as the non-transcribed strand, with U in place of T. Template 3′ TAC 5′ gives mRNA 5′ AUG 3′.
• “A and T are held together by three hydrogen bonds.” Correct A–T has two hydrogen bonds; C–G has three. DNA with more C–G pairs needs more energy to separate its strands.
• “Adenine and thymine are the purines.” Correct The purines are adenine and guanine (double ring). Cytosine, thymine and uracil are pyrimidines (single ring). Every pair is one of each.
• “The lagging strand is made in fragments because it is copied more slowly.” Correct DNA polymerase adds nucleotides only to the 3′ end, so it builds 5′ → 3′. On one template that direction is towards the fork (continuous); on the other it is away from the fork, so the strand can only be made in short lengths.
• “DNA ligase joins the new nucleotides together.” Correct DNA polymerase joins the nucleotides. DNA ligase joins the fragments of the lagging strand to each other.
• “The codon is on the tRNA.” Correct Codons are on the mRNA; the anticodon is on the tRNA and is complementary to one codon.
• “Deleting one base changes one amino acid.” Correct Deleting or inserting one base shifts the reading frame: every triplet after it is read differently (a frameshift). Only a substitution is limited to one triplet.
• “A mutation always changes the protein.” Correct A gene mutation may result in an altered polypeptide. A substitution that gives a codon for the same amino acid (the code is degenerate) leaves it unchanged.
• “DNA contains ribose.” Repair DNA contains deoxyribose; RNA and ATP contain ribose.
• “The phosphate is attached to carbon 1 and the base to carbon 5.” Repair The other way round: the phosphate on C5′, the base on C1′.
• “Adenine and thymine are purines.” Repair The purines are adenine and guanine (double ring); cytosine, thymine and uracil are pyrimidines (single ring).
• “A and T are joined by three hydrogen bonds.” Repair A–T has two; C–G has three.
• “The bases are joined by phosphodiester bonds.” Repair Phosphodiester bonds join the sugar of one nucleotide to the phosphate of the next along a strand; the bases of the two strands are held by hydrogen bonds.
• “The two strands run in the same direction.” Repair They are antiparallel: 5′ → 3′ and 3′ → 5′.
• “Replication is semi-conservative because half of each strand is new.” Repair Each new molecule has one whole old strand and one whole new strand.
• “DNA ligase joins the nucleotides of the new strand.” Repair DNA polymerase joins the nucleotides; DNA ligase joins the fragments of the lagging strand.
• “The lagging strand is made discontinuously because it is made more slowly.” Repair It is discontinuous because DNA polymerase adds nucleotides only 5′ → 3′, which on that template is away from the fork.
• “The mRNA has the same sequence as the template strand.” Repair mRNA is complementary to the template strand; it has the same sequence as the non-transcribed strand, with U for T.
• “RNA polymerase makes the mRNA 3′ → 5′, because it reads the template 3′ → 5′.” Repair It reads the template 3′ → 5′ and so builds the RNA 5′ → 3′, like every new strand.
• “tRNA carries the codon.” Repair tRNA carries the anticodon and one specific amino acid; the codon is on the mRNA.
• “The ribosome makes the peptide bonds between the tRNAs.” Repair The peptide bond forms between the amino acids the tRNAs carry, by condensation, catalysed by the ribosome.
• “Exons are removed from the primary transcript.” Repair Introns (non-coding) are removed; exons (coding) are joined. In eukaryotes, in the nucleus.
• “Every mutation changes the protein.” Repair A gene mutation may alter the polypeptide; a silent substitution, or a change in an intron, does not.
• “A deletion changes one amino acid.” Repair Deleting one nucleotide causes a frameshift that can change every amino acid after it; only a substitution is limited to one triplet.

• Read the command word before you decide how much to write. This syllabus has seventeen of them: assess, calculate, comment, compare, contrast, define, describe, determine, discuss, explain, give, identify, outline, predict, sketch, state and suggest. State, give and identify want a fact and nothing more. Define wants a precise meaning. Outline wants the main points only; describe wants the points or the features in full — and when you describe a graph, the trend with figures quoted from it. Explain wants the reasons and the mechanism — a describe-level answer to an explain question is incomplete however well written it is. Compare wants similarities and differences, each stated for both things side by side; contrast wants differences only. Discuss wants the issue written about in depth, in a structured way; assess wants an informed judgement. Suggest asks you to apply what you know to a situation where there is a range of valid responses, making proposals or putting forward considerations, so any sound biological reasoning is creditable.
• Interleave with the chapters that use this one. When you reach topic 12, re-answer “describe the structure of ATP” before learning how it is made; at 16.2.6, re-derive the sickle cell codon change (GAG → GUG) before learning its consequences; at 16.3, re-state the role of RNA polymerase before learning how transcription is controlled; in topic 19, re-state the roles of DNA ligase and complementary base pairing before meeting them in gene technology. Recalling a topic inside a new context is worth more than another pass over this chapter on its own; at A Level, Paper 4 assumes the whole of the AS content, so nothing here is ever finished with.

• Cambridge International AS & A Level Biology 9700 has five components. Topic 6 is AS Level content, so it is examined in Papers 1, 2 and 3. AS Level content: examined in Paper 1 (multiple choice), Paper 2 (AS structured) and, as practical context, Paper 3. Assumed knowledge for Papers 4 and 5. AS Level candidates take Papers 1, 2 and 3; A Level candidates take all five, either staged over two years (Papers 1–3 in year one, Papers 4 and 5 in year two) or together in one series. Examinations are available in the June and November series, and in March in India.
• Across both the AS Level and the A Level the assessment objectives are weighted AO1 40% (knowledge and understanding), AO2 40% (handling, applying and evaluating information) and AO3 20% (experimental skills and investigations). AS candidates are graded a–e; A Level candidates A*–E. There is no data booklet in Biology. At A Level, the statistical formulae (Hardy–Weinberg, the Lincoln index, Simpson’s index, standard deviation, standard error, 95% confidence intervals, the χ² test, the t-test, and Pearson’s and Spearman’s correlation) are printed in a question when it needs them, and so are the tables of critical values; degrees of freedom you must work out yourself. Everything else — magnification, surface area to volume, RQ, Rf, rates — you must recall, and this chapter says which is which.
• A multiple-choice item turns on one precise detail: which bases are purines, how many hydrogen bonds a pair has, which way a new strand grows, which strand the mRNA matches, which enzyme joins fragments, what a frameshift does. A structured question asks you to describe DNA structure or replication, to explain why the lagging strand is discontinuous, to state the roles of the molecules named in 6.2.3, or to explain how a mutation changes a polypeptide.
• A base sequence to transcribe and translate from a codon table the question supplies; a mutated sequence to compare with the original; a DNA ladder or replication fork to label; base percentages to complete; the density bands of DNA over several generations to interpret. The numerical skills are percentages, counts of hydrogen bonds, codons and amino acids, and nucleotide lengths — all recall relationships.
• The syllabus names no practical for this topic, so DNA extraction is the closest context. As an investigation the independent variable is detergent concentration, made by proportional dilution; the dependent variable is the height of the DNA layer in ethanol, read to 1 mm; fruit mass, salt, volumes, ethanol temperature and time are standardised; a no-detergent control shows the detergent is needed; the main error is judging the edge of an uneven layer.
• Read the command word before you decide how much to write. This syllabus has seventeen of them: assess, calculate, comment, compare, contrast, define, describe, determine, discuss, explain, give, identify, outline, predict, sketch, state and suggest. State, give and identify want a fact and nothing more. Define wants a precise meaning. Outline wants the main points only; describe wants the points or the features in full — and when you describe a graph, the trend with figures quoted from it. Explain wants the reasons and the mechanism — a describe-level answer to an explain question is incomplete however well written it is. Compare wants similarities and differences, each stated for both things side by side; contrast wants differences only. Discuss wants the issue written about in depth, in a structured way; assess wants an informed judgement. Suggest asks you to apply what you know to a situation where there is a range of valid responses, making proposals or putting forward considerations, so any sound biological reasoning is creditable.