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Molecular Basis of Inheritance
Start here: why this chapter matters
This is the fifth chapter of NCERT's Class 12 Biology textbook (pages 79–109 of the 2026-27 reprint), the second of Unit VII, Genetics and Evolution. It has ten sections — the DNA (5.1), the search for genetic material (5.2), the RNA world (5.3), replication (5.4), transcription (5.5), the genetic code (5.6), translation (5.7), regulation of gene expression (5.8), the Human Genome Project (5.9) and DNA fingerprinting (5.10) — with Figures 5.1–5.16, an unnumbered central-dogma sketch, Table 5.1 (the codon chart), a summary and 14 exercise questions. Every DNA and RNA sequence on this page is generated and checked in the source file, so you can trust the pairings.
- Neighbouring chapters: the previous chapter, Principles of Inheritance and Variation, gave the rules (Mendel, linkage, sickle-cell as a point mutation); this one gives the molecule. The next, Evolution, uses the RNA world, mutation and DNA polymorphism; the later biotechnology chapters use restriction enzymes, vectors, PCR and the origin of replication met here. Class 11 Biomolecules introduced nucleotides.
- Prelims — science: UPSC has asked about tRNA as the adapter (1985), base pairing (1985), genes acting through protein synthesis (1986), complementarity as DNA's key feature (2001), the operon concept (1998), genetics pioneers including Khorana and Kornberg (2001), James Watson (2008), DNA fingerprinting (1991, 1997, 2000), genome sequencing (1997, 2017, 2026), the transcriptome (2016), microsatellite DNA (2023) and viruses that infect bacteria (2025).
- GS3 Science and Technology: genome sequencing, genomic medicine, forensic DNA and bioinformatics all start here. GS2: DNA testing and privacy (Mains 2024) — the science of a paternity test is in Section 10.
| Word | What it means here |
|---|---|
| Nucleoside / nucleotide | Base + sugar (e.g. adenosine) / nucleoside + phosphate (the monomer of DNA or RNA) |
| Purine / pyrimidine | Two-ring bases A and G / one-ring bases C, T (DNA) and U (RNA) |
| Base pair (bp) | A paired with T, or G with C, across the two strands; DNA length is counted in bp |
| 5′ and 3′ ends | The free phosphate end and the free 3′-OH end of a strand; strands are written 5′→3′ |
| Nucleosome / chromatin | DNA wound round eight histones / the whole DNA–protein thread in the nucleus |
| Replication / transcription / translation | DNA → DNA / DNA → RNA / RNA → protein |
| Template / coding strand | The strand read by RNA polymerase (3′→5′) / the other strand, whose sequence the RNA copies |
| Exon / intron | Part of a gene kept in mature RNA / part removed by splicing |
| Codon / anticodon | Three-base word in mRNA / its complementary three bases on tRNA |
| Operon | A set of bacterial genes under one promoter and operator, switched together |
| Polymorphism / VNTR | A DNA variant common in a population (frequency above 0.01) / a variable number of tandem repeats |
At a glance — the six ideas to carry away
- DNA: polymer of deoxyribonucleotides (base + deoxyribose + phosphate); double helix (Watson and Crick, 1953, from Wilkins and Franklin's X-ray data): antiparallel strands, A=T (2 H-bonds), G≡C (3), purine opposite pyrimidine, right-handed, pitch 3.4 nm, ~10 bp per turn, 0.34 nm per bp. Chargaff: A/T = G/C = 1.
- Packaging: 6.6 × 10⁹ bp ≈ 2.2 m per diploid cell; DNA (−) wraps a histone octamer (+; lysine, arginine) → nucleosome (~200 bp) → beads-on-string → chromatin fibre (NHC proteins) → chromosome. Euchromatin active, heterochromatin inactive. Central dogma: DNA → RNA → protein.
- Genetic material: Griffith 1928 (transforming principle, Streptococcus pneumoniae); Avery–MacLeod–McCarty 1944 (only DNase stops transformation); Hershey–Chase 1952 (³²P DNA enters, ³⁵S protein does not). RNA is the genetic material in TMV, Qβ; RNA world: RNA first, DNA more stable.
- Replication: semiconservative (Meselson–Stahl 1958, ¹⁵N/¹⁴N, CsCl; Taylor, Vicia faba). DNA polymerase works 5′→3′: continuous on one template, discontinuous on the other (joined by ligase); needs an origin. Transcription: template strand 3′→5′; promoter, structural gene, terminator; σ starts, ρ stops.
- Eukaryotes: RNA pol I (rRNA 28S, 18S, 5.8S), II (hnRNA), III (tRNA, 5S rRNA, snRNA); split genes — splicing, capping, tailing. Code: triplet, 64 = 61 + 3 stop (UAA, UAG, UGA), degenerate, no punctuation, nearly universal, AUG = Met/start (Gamow, Khorana, Nirenberg, Ochoa). tRNA = adapter; ribosome's rRNA is a ribozyme.
- lac operon (Jacob and Monod): i (repressor), z (β-galactosidase), y (permease), a (transacetylase); lactose = inducer; negative regulation. HGP 1990–2003: 3164.7 Mbp, ~30,000 genes (NCERT), <2% codes protein, 99.9% identical, 1.4 million SNPs. DNA fingerprinting (Alec Jeffreys): VNTR mini-satellites, Southern blot; forensics, paternity.
1. DNA: the polynucleotide chain and the double helix
Size. DNA length is counted in nucleotides or base pairs and is characteristic of an organism: bacteriophage φX174 has 5386 nucleotides, bacteriophage lambda 48,502 bp, Escherichia coli 4.6 × 10⁶ bp, and the haploid human genome 3.3 × 10⁹ bp.
The chain. A nucleotide has three parts: a nitrogenous base, a pentose sugar (ribose in RNA, deoxyribose in DNA) and a phosphate. Bases are purines (adenine, guanine) or pyrimidines (cytosine, thymine, uracil); cytosine is in both nucleic acids, thymine only in DNA, uracil in its place in RNA. A base joined to the 1′ carbon of the sugar by an N-glycosidic bond makes a nucleoside (adenosine, guanosine, cytidine, uridine; deoxy- forms in DNA); a phosphate on the 5′ carbon makes a nucleotide. Nucleotides join by 3′–5′ phosphodiester bonds into a chain whose backbone is sugar–phosphate, with bases projecting from it; one end has a free 5′ phosphate (the 5′ end), the other a free 3′-OH (the 3′ end). RNA has an extra –OH at the 2′ carbon of every ribose, and uracil instead of thymine (5-methyl uracil).
The discovery. Friedrich Miescher (NCERT spells it ‘Meischer’) first identified DNA as an acidic substance in the nucleus in 1869 and called it ‘nuclein’. Its structure stayed unknown until 1953, when James Watson and Francis Crick proposed the double helix from X-ray diffraction data of Maurice Wilkins and Rosalind Franklin. A hallmark was base pairing, supported by Erwin Chargaff's observation that in double-stranded DNA the ratios A : T and G : C are constant and equal to one. Because the strands are complementary, one strand's sequence predicts the other's, and each could serve as a template for an identical daughter molecule.
- Two polynucleotide chains; sugar–phosphate backbone outside, bases inside.
- The chains are antiparallel: one runs 5′→3′, the other 3′→5′.
- Bases pair by hydrogen bonds: A with T by two, G with C by three. A purine always faces a pyrimidine, which keeps the distance between strands almost uniform.
- The chains coil right-handedly; the pitch is 3.4 nm with roughly 10 bp per turn, so about 0.34 nm between base pairs.
- Base pairs stack on each other, which, with the H-bonds, stabilises the helix.
The central dogma. Soon after, Francis Crick proposed that genetic information flows DNA → RNA → protein. In some viruses information flows from RNA to DNA — reverse transcription (NCERT's in-text question).
- Nucleoside = base + sugar; nucleotide = base + sugar + phosphate. Adenine, thymine, uracil and cytosine are bases; cytidine and guanosine are nucleosides (exercise 1).
- Purines: A, G (two rings). Pyrimidines: C, T, U (one ring). Mnemonic: ‘pure As Gold’.
- Chargaff's rule holds for double-stranded DNA across both strands: A = T, G = C, purines = pyrimidines. It does not say A + T = G + C, and it does not hold within one strand or in single-stranded genomes.
- Pitch 3.4 nm per turn; 0.34 nm per base pair — do not swap them.
- RNA differs from DNA chemically in two ways: ribose with a 2′-OH, and uracil instead of thymine.
- DNA is right-handed in the Watson–Crick model.
- Watson, Crick and Wilkins shared the 1962 Nobel Prize in Physiology or Medicine; Rosalind Franklin had died in 1958, and Nobel Prizes are not awarded posthumously.
- A G≡C pair, with three hydrogen bonds, holds more strongly than A=T, so DNA richer in G and C separates (‘melts’) at a higher temperature.
- Reverse transcription is carried out by the enzyme reverse transcriptase, found in retroviruses such as HIV (discovered by Temin and Baltimore, 1970).
2. Packaging: from two metres of DNA to a chromosome
Multiplying the number of base pairs in a typical mammalian cell by the spacing between them gives 6.6 × 10⁹ bp × 0.34 × 10⁻⁹ m/bp ≈ 2.2 metres — far longer than the nucleus (about 10⁻⁶ m). In prokaryotes such as E. coli, which lack a defined nucleus, the negatively charged DNA is held by positively charged proteins in a region called the nucleoid, organised in large loops.
In eukaryotes, histones — basic proteins rich in the positively charged amino acids lysine and arginine — form a unit of eight, the histone octamer. Negatively charged DNA wraps around it to form a nucleosome, which typically contains 200 bp. Nucleosomes are the repeating units of chromatin, seen under the electron microscope as ‘beads-on-string’. Chromatin is packed into fibres that coil and condense at metaphase into chromosomes; this higher-level packing needs non-histone chromosomal (NHC) proteins. Loosely packed, lightly staining euchromatin is transcriptionally active; densely packed, dark-staining heterochromatin is inactive.
| NCERT's in-text calculation | Working | Answer |
|---|---|---|
| Length of DNA in a mammalian cell | 6.6 × 10⁹ bp × 0.34 × 10⁻⁹ m | ≈ 2.2 m |
| Base pairs in E. coli DNA 1.36 mm long | 1.36 × 10⁻³ m ÷ 0.34 × 10⁻⁹ m | 4.0 × 10⁶ bp |
| Nucleosomes in a mammalian cell | 6.6 × 10⁹ bp ÷ 200 bp | ≈ 3.3 × 10⁷ |
- Histones are basic and positive (lysine, arginine); DNA is acidic and negative (phosphates). Opposite charges hold the nucleosome together.
- Octamer = 8 histone molecules; H1 sits outside it. A nucleosome holds about 200 bp.
- Euchromatin = loose, light, active; heterochromatin = dense, dark, inactive.
- Prokaryotes have a nucleoid, not a nucleus, and no nucleosomes of this kind.
- NCERT inconsistency: 1.36 mm of E. coli DNA gives 4.0 × 10⁶ bp, but page 80 quotes 4.6 × 10⁶ bp (which would be about 1.56 mm). For the in-text question show the working and write 4 × 10⁶ bp; for ‘genome size of E. coli’ write 4.6 × 10⁶ bp.
3. The search for the genetic material
By 1926 genetics had narrowed the search to the chromosomes, but not to a molecule. Transforming principle. In 1928 Frederick Griffith worked with Streptococcus pneumoniae (pneumococcus). Its S strain forms smooth, shiny colonies because it has a mucous (polysaccharide) coat and is virulent; the R strain forms rough colonies, has no coat and does not cause pneumonia. Heat-killed S cells alone were harmless, but a mixture of heat-killed S and live R cells killed mice, and living S bacteria were recovered from them. Some ‘transforming principle’ from the dead S cells had let R cells make a coat — a transfer of genetic material, though Griffith could not say what it was.
Biochemical characterisation. Until then the genetic material was widely thought to be protein. Oswald Avery, Colin MacLeod and Maclyn McCarty (work of 1933–44) purified proteins, DNA and RNA from heat-killed S cells and found that DNA alone transformed R cells. Proteases and RNases did not stop transformation; DNase did. They concluded DNA is the hereditary material, but not everyone was convinced.
The unequivocal proof (1952). Alfred Hershey and Martha Chase used bacteriophages, viruses that infect bacteria and make the cell build new viruses from the viral genetic material. They grew some phages with radioactive phosphorus (which labels DNA, since protein has no phosphorus) and others with radioactive sulphur (which labels protein, since DNA has no sulphur). After the phages attached to E. coli, a blender knocked off the viral coats and a centrifuge separated bacteria from virus particles. Bacteria infected by ³²P phages were radioactive; those infected by ³⁵S phages were not — so DNA, not protein, passes from virus to bacterium.
DNA versus RNA. In some viruses, such as tobacco mosaic virus and bacteriophage Qβ, RNA is the genetic material. A genetic material must (i) replicate, (ii) be chemically and structurally stable, (iii) allow slow mutation for evolution, and (iv) express itself as Mendelian characters. Both nucleic acids can direct their own copying by base pairing; proteins fail even the first test. The table sets out the rest.
| Criterion | DNA | RNA |
|---|---|---|
| Replication | yes — complementary strands | yes — base pairing |
| Stability | more stable: no reactive 2′-OH; double-stranded, so separated strands can re-pair (why heat in Griffith's experiment did not destroy it); thymine adds stability | labile: the 2′-OH is reactive; RNA can be catalytic, hence reactive |
| Mutation | slower | faster — RNA viruses, with short life spans, mutate and evolve faster |
| Expression | depends on RNA to make protein | can code for protein directly; the protein-making machinery evolved around RNA |
| Best for | storing information | transmitting information |
RNA world. NCERT states that RNA was the first genetic material: essential processes — metabolism, translation, splicing — evolved around RNA, which acted both as genetic material and as a catalyst (some reactions are catalysed by RNA, not protein). Being catalytic it was reactive and unstable, so DNA evolved from RNA with chemical changes that made it more stable, and its double strand allowed repair.
- Griffith (1928) showed transformation but not the molecule; Avery–MacLeod–McCarty (1944) identified DNA; Hershey–Chase (1952) gave the unequivocal proof.
- ³²P labels DNA, ³⁵S labels protein — phosphorus is in DNA's backbone, sulphur in protein's amino acids (cysteine, methionine). 15N in Meselson–Stahl is not radioactive.
- DNA vs DNase (in-text): DNA is the nucleic acid; DNase is the enzyme (a protein) that digests it.
- The heat-killed S cells did not ‘come alive’; their DNA transformed living R cells.
- The RNA world is a well-supported hypothesis about life's origin; NCERT states it as fact — in answers write ‘the RNA-world hypothesis holds that…’.
- The Avery, MacLeod and McCarty paper was published in 1944; Hershey shared the 1969 Nobel Prize with Delbrück and Luria.
- RNA catalysts are called ribozymes; the peptide-bond-forming rRNA of the ribosome (Section 7) is the best-known example and a key piece of evidence for the RNA world.
- Many human pathogens have RNA genomes — influenza, measles, HIV, SARS-CoV-2 — which is one reason they evolve quickly and vaccines need updating.
4. Replication: semiconservative copying
Watson and Crick saw at once that specific pairing ‘suggests a possible copying mechanism’ (1953): the strands separate and each acts as a template for a new complementary strand, so each daughter molecule has one parental and one new strand — semiconservative replication.
The experimental proof (1958). Matthew Meselson and Franklin Stahl grew E. coli for many generations on ¹⁵NH₄Cl, so all DNA contained the heavy, non-radioactive isotope ¹⁵N, and could be told from normal DNA by caesium chloride (CsCl) density-gradient centrifugation. They moved the cells to ¹⁴NH₄Cl and sampled DNA as the cells divided (every 20 minutes). After one generation all DNA was of hybrid (intermediate) density; after two, half was hybrid and half light. Similar experiments with radioactive thymidine on Vicia faba (faba bean) by Taylor and colleagues (1958) showed that chromosomes too replicate semiconservatively.
Machinery and enzymes. The main enzyme is DNA-dependent DNA polymerase, which uses a DNA template to join deoxynucleotides. It must be fast and accurate: E. coli's 4.6 × 10⁶ bp are copied in about 18 minutes (compare the human diploid 6.6 × 10⁹ bp), and mistakes become mutations. Replication is energetically expensive: deoxyribonucleoside triphosphates act both as substrates and as the energy source (their two terminal phosphates are high-energy, as in ATP).
Long DNA cannot be unwound along its whole length, so copying happens in a small opening, the replication fork. Polymerases add nucleotides only in the 5′→3′ direction. So on the template with polarity 3′→5′ synthesis is continuous; on the template with polarity 5′→3′ it is discontinuous, and the fragments are joined by DNA ligase. Polymerases cannot start on their own, and replication begins only at a definite origin of replication — which is why a piece of DNA propagated in recombinant-DNA work needs a vector that supplies an origin. In eukaryotes replication takes place in the S phase; if the cell fails to divide after replication, polyploidy results.
| Number (NCERT) | Check (our calculation) |
|---|---|
| E. coli: 4.6 × 10⁶ bp in 18 min ‘≈ 2000 bp per second’ | 4.6 × 10⁶ ÷ 1080 s ≈ 4259 bp/s in all; with two forks moving out from one origin, ≈ 2130 bp/s per fork — so NCERT's figure is a per-fork rate |
| Meselson–Stahl at 80 minutes | 80 ÷ 20 = 4 generations → 2 hybrid : 14 light = 1/8 : 7/8 |
- Semiconservative = each daughter has one old and one new strand. Conservative (both old together) and dispersive models were ruled out by Meselson–Stahl.
- ¹⁵N is a heavy, stable isotope separated by density (CsCl), not detected by radioactivity.
- DNA polymerase synthesises only 5′→3′. Continuous synthesis on the 3′→5′ template; discontinuous on the 5′→3′ template; ligase joins the pieces.
- dNTPs are both substrate and energy source.
- NCERT number to handle: ‘≈ 2000 bp per second’ is about right per replication fork, not for the whole chromosome (about 4300 bp/s from the numbers given).
- The two original ¹⁵N strands survive in exactly two hybrid molecules in every later generation.
- E. coli has a single origin (oriC); replication runs in both directions from it, giving two forks.
- The continuously made strand is called the leading strand, the other the lagging strand, and its pieces Okazaki fragments. Helicase unwinds the helix, topoisomerase relieves twisting, and primase lays down a short RNA primer because DNA polymerase cannot start a new chain.
- Arthur Kornberg isolated the first DNA polymerase, from E. coli (1956), and shared the 1959 Nobel Prize with Severo Ochoa.
5. Transcription: DNA to RNA
Transcription copies genetic information from one strand of DNA into RNA, again by complementarity, except that adenine now pairs with uracil. Unlike replication, only a segment of DNA and only one strand are copied. Why not both? The two RNAs would differ in sequence (complementary is not identical), so one DNA segment would code for two different proteins; and two complementary RNAs made together would pair into double-stranded RNA that could not be translated.
The transcription unit has three regions: a promoter, the structural gene and a terminator. Since DNA-dependent RNA polymerase also works only 5′→3′, the strand with polarity 3′→5′ is the template strand. The other strand, 5′→3′, has the same sequence as the RNA (with T for U) and is displaced; though it codes for nothing, it is called the coding strand, and all reference points are given relative to it. The promoter lies upstream (towards the 5′ end of the coding strand) and binds RNA polymerase — its position defines which strand is template; swapping promoter and terminator would swap the definitions. The terminator lies downstream (3′) and usually ends transcription. Further regulatory sequences may lie upstream or downstream.
Transcription unit and the gene. A gene is the functional unit of inheritance, but hard to define as a DNA stretch: DNA coding for tRNA or rRNA is also a gene. A cistron is a DNA segment coding for one polypeptide; structural genes are monocistronic (mostly eukaryotes) or polycistronic (mostly bacteria). Eukaryotic genes are split: coding or expressed sequences, exons, appear in mature RNA; intervening sequences, introns, do not. Promoters and regulatory sequences also affect inheritance, so they are loosely called regulatory genes even though they code for no RNA or protein.
In bacteria three major RNAs — mRNA (template), tRNA (brings amino acids and reads the code) and rRNA (structural and catalytic) — are all made by a single DNA-dependent RNA polymerase. It binds the promoter (initiation), uses nucleoside triphosphates to build RNA by complementarity while opening the helix (elongation; only a short stretch of RNA stays bound), and at the terminator the RNA and polymerase fall off (termination). The polymerase itself can only elongate: it associates briefly with the sigma (σ) factor to initiate and the rho (ρ) factor to terminate. Bacterial mRNA needs no processing and there is no nuclear membrane, so translation can begin before transcription ends — the two are coupled.
In eukaryotes there are two extra complexities. (i) At least three RNA polymerases in the nucleus (besides those of organelles) divide the work, as in the table. (ii) The primary transcript contains exons and introns and is non-functional; splicing removes introns and joins exons in order. The hnRNA is also capped — an unusual nucleotide, methyl guanosine triphosphate, is added to the 5′ end — and tailed — 200–300 adenylate residues are added to the 3′ end without a template. The fully processed RNA, now mRNA, leaves the nucleus. Split genes are probably an ancient feature, and splicing reflects the dominance of the RNA world.
| Eukaryotic nuclear enzyme | Transcribes |
|---|---|
| RNA polymerase I | rRNAs — 28S, 18S and 5.8S |
| RNA polymerase II | the precursor of mRNA, heterogeneous nuclear RNA (hnRNA) |
| RNA polymerase III | tRNA, 5S rRNA and snRNAs (small nuclear RNAs) |
- Template strand (3′→5′) is read; coding strand (5′→3′) has the RNA's sequence — the RNA is the coding strand with U for T, and the complement of the template (exercise 4: coding 5′-ATGC…-3′ → mRNA 5′-AUGC…-3′).
- Promoter = upstream, binds RNA polymerase; terminator = downstream. Directions are named on the coding strand.
- σ initiates, ρ terminates; the core polymerase only elongates.
- Pol I → big rRNAs (28S, 18S, 5.8S); pol II → hnRNA/mRNA; pol III → tRNA, 5S rRNA, snRNA. 5S is the odd one out — made by pol III.
- Exons stay in mature RNA, introns are removed — even an exon can be non-coding at its ends. Bacteria: no introns, no capping, coupled transcription–translation.
- Monocistronic = eukaryotes mostly; polycistronic = bacteria (e.g. the lac operon).
- The cap is usually written 7-methylguanosine (m⁷G); it protects mRNA and helps ribosomes bind. Splicing is carried out by the spliceosome, built of snRNAs and proteins.
- Alternative splicing lets one gene give several proteins by joining exons in different combinations — one reason humans have far fewer genes than once expected.
- Split genes were discovered in 1977 (Phillip Sharp and Richard Roberts; Nobel Prize 1993).
6. The genetic code, mutations and tRNA
Copying nucleic acid into nucleic acid is easy to picture by complementarity, but no complementarity exists between nucleotides and amino acids. Evidence that changes in genetic material changed amino acids led to the idea of a genetic code. Deciphering it needed physicists, organic chemists, biochemists and geneticists. The physicist George Gamow argued that 4 bases coding for 20 amino acids need combinations, and that a triplet code (4³ = 64 codons) would suffice. Har Gobind Khorana's chemical method made RNAs of defined base combinations (homopolymers and copolymers); Marshall Nirenberg's cell-free system for protein synthesis finally cracked the code; Severo Ochoa's enzyme, polynucleotide phosphorylase, polymerised RNA of defined sequence without a template. The result was a checkerboard of codons.
- The codon is a triplet: 61 codons code for amino acids; 3 code for none and act as stop codons.
- Some amino acids have more than one codon — the code is degenerate.
- Codons are read contiguously: there is no punctuation.
- The code is nearly universal — UUU means phenylalanine from bacteria to humans — with some exceptions in mitochondrial codons and some protozoans.
- AUG has two jobs: it codes for methionine and is the initiator codon.
- UAA, UAG, UGA are stop (terminator) codons.
NCERT's in-text exercise: AUG UUU UUC UUC UUU UUU UUC translates to Met-Phe-Phe-Phe-Phe-Phe-Phe. Going back from Met-Phe×6 to the mRNA is harder: phenylalanine has two codons (UUU, UUC), so there are 2⁶ = 64 possible mRNAs. Forward translation is unambiguous; reverse is not — the code is specific but degenerate (both checked in the source file).
Mutations and the code. Large deletions or rearrangements can remove or add whole genes. A point mutation changes one base pair: in the β-globin gene, one change turns glutamate into valine and causes sickle-cell anaemia (GAG → GUG in mRNA; Chapter 4). Inserting or deleting one or two bases shifts the reading frame from that point — a frame-shift mutation — whereas inserting or deleting three (or a multiple of three) adds or removes whole codons and leaves the frame intact after them. NCERT's sentence of three-letter words shows it:
| Change to RAM HAS RED CAP | Read in threes (computed) | Frame after the change |
|---|---|---|
| insert B | RAM HAS BRE DCA P | shifted |
| insert BI | RAM HAS BIR EDC AP | shifted |
| insert BIG | RAM HAS BIG RED CAP | restored — one extra word |
| delete R | RAM HAS EDC AP | shifted |
| delete RE | RAM HAS DCA P | shifted |
| delete RED | RAM HAS CAP | restored — one word lost |
tRNA, the adapter. Francis Crick reasoned that amino acids cannot read the code themselves, so an adapter must read a codon on one side and carry an amino acid on the other. tRNA — then called soluble RNA (sRNA) — was known before the code but its adapter role came later. It has an anticodon loop with bases complementary to the codon and an amino-acid acceptor end. tRNAs are specific for each amino acid; a special initiator tRNA starts translation; there are no tRNAs for stop codons. Its secondary structure looks like a clover leaf; the real 3-D molecule is a compact inverted L.
- 64 codons = 61 sense + 3 stop; there are 20 amino acids. AUG is both Met and start; there is no ‘start-only’ codon in NCERT's scheme.
- Degenerate = one amino acid, several codons. Unambiguous/specific = one codon, one amino acid. Do not swap them.
- ‘Universal’ is nearly universal: mitochondria and some protozoans differ.
- Frame-shift = insertion or deletion of 1 or 2 bases (not 3). A point substitution (sickle-cell) changes one codon only.
- The anticodon is on tRNA, the codon on mRNA; they pair antiparallel. No tRNA reads stop codons — release factors do.
- Khorana: chemical synthesis of defined RNAs; Nirenberg: cell-free system; Ochoa: polynucleotide phosphorylase; Gamow: argued for a triplet. UPSC 2001 keyed Khorana for ‘establishing the complete genetic code’.
- Khorana, Nirenberg and Robert Holley (who worked out a tRNA's structure) shared the 1968 Nobel Prize in Physiology or Medicine.
- Nirenberg and Matthaei's first result (1961) was that poly-U RNA makes polyphenylalanine — UUU = Phe.
- In human mitochondria, UGA codes for tryptophan instead of stop — an example of the code being only nearly universal.
7. Translation: RNA to protein
Translation polymerises amino acids into a polypeptide in the order set by the mRNA's bases; amino acids are joined by peptide bonds, whose formation needs energy. So first the amino acids are activated with ATP and linked to their own tRNA — charging of tRNA, or aminoacylation. Two charged tRNAs brought close together favour peptide-bond formation, and a catalyst speeds it.
The ribosome is the protein factory: structural RNAs plus about 80 different proteins, existing when inactive as a large and a small subunit. Translation begins when the small subunit meets an mRNA. The large subunit has two sites where successive amino acids bind close enough to form a peptide bond, and the ribosome itself catalyses the bond — in bacteria the 23S rRNA is the enzyme, a ribozyme. A translational unit is the mRNA stretch from the start codon (AUG) to a stop codon; untranslated regions (UTRs) lie before the start (5′ UTR) and after the stop (3′ UTR) and are needed for efficient translation.
- Transcription (DNA → RNA, nucleus in eukaryotes, RNA polymerase) vs translation (RNA → protein, cytoplasm, ribosome). Exam questions swap them.
- Charging (aminoacylation) uses ATP and happens before the tRNA reaches the ribosome.
- The peptide bond is made by rRNA — a ribozyme — not by a ribosomal protein.
- UTRs are part of the mRNA but are not translated; they lie outside AUG…stop.
- Two roles of the ribosome (exercise 9): it binds mRNA and provides the sites where charged tRNAs meet codons, and it catalyses peptide-bond formation.
- NCERT's ‘about 80 proteins’ fits a eukaryotic ribosome; bacterial ribosomes have fewer (Beyond NCERT).
- Ribosomes are named by sedimentation: bacterial 70S (50S + 30S subunits) and eukaryotic cytoplasmic 80S (60S + 40S); S values do not add. The two sites NCERT mentions are usually called the P (peptidyl) and A (aminoacyl) sites, with an E (exit) site as well.
- Many antibiotics (e.g. streptomycin, tetracycline) work by blocking bacterial 70S ribosomes, which differ from ours.
- Several ribosomes can read one mRNA at once — a polysome.
8. Regulation of gene expression: the lac operon
Gene expression, ending in a polypeptide, can be regulated at several levels. In eukaryotes: (i) transcription (forming the primary transcript), (ii) processing (regulating splicing), (iii) transport of mRNA from nucleus to cytoplasm, and (iv) translation. Metabolic, physiological or environmental conditions decide which genes are expressed; embryonic development and differentiation also rest on coordinated gene regulation. If E. coli has no lactose to use, it need not make β-galactosidase, the enzyme that splits lactose into galactose and glucose.
In prokaryotes the main control point is the rate of transcriptional initiation. Accessory proteins act on RNA polymerase at the promoter — positively (activators) or negatively (repressors). Often a repressor binds an operator next to the promoter; each operon has its own operator and repressor (the lac operator binds only the lac repressor). In an operon, a polycistronic structural gene is controlled by a common promoter and regulatory genes — lac, trp, ara, his, val operons are examples.
The lac operon was worked out by the geneticist François Jacob and the biochemist Jacques Monod — the first transcriptionally regulated system explained. It has one regulatory gene, i (from ‘inhibitor’, not ‘inducer’), coding for the repressor, and three structural genes: z (β-galactosidase), y (permease, which lets β-galactosides into the cell) and a (transacetylase) — all needed for lactose metabolism. The repressor is made all the time (constitutively) and binds the operator, blocking RNA polymerase. Lactose, the substrate of β-galactosidase, is the inducer: when glucose, the preferred carbon source, is absent and lactose is supplied, lactose enters through permease (a very low level of expression is always present, or it could not enter), and lactose or allolactose binds and inactivates the repressor, so RNA polymerase transcribes the operon. This is regulation of enzyme synthesis by its substrate, and control by a repressor is negative regulation; the lac operon is also under positive regulation, beyond NCERT's scope.
- i stands for inhibitor; its product, the repressor, is made constitutively.
- z = β-galactosidase, y = permease, a = transacetylase — in that order.
- The repressor binds the operator, not the promoter; RNA polymerase binds the promoter.
- The inducer is lactose (or allolactose); glucose and galactose cannot induce the operon.
- Lac regulation by the repressor is negative regulation; the operon shuts down again once lactose is exhausted.
- Operon concept = Jacob and Monod (UPSC 1998); one gene–one enzyme = Beadle and Tatum; mutation theory = de Vries.
- Allolactose, a by-product of β-galactosidase acting on lactose, is the natural inducer; lab work often uses IPTG, which induces but is not broken down.
- The positive control NCERT leaves out is catabolite repression: when glucose is low, cAMP rises and the CAP–cAMP complex helps RNA polymerase bind — so the operon is fully on only with lactose present and glucose absent.
- Jacob, Monod and André Lwoff shared the 1965 Nobel Prize. The trp operon is the classic repressible operon, switched off by its end-product, tryptophan.
9. The Human Genome Project
If genetic make-up lies in DNA sequence, then individuals who differ must differ in sequence somewhere. With cloning and fast sequencing available, the Human Genome Project (HGP) was launched in 1990 — a ‘mega project’. At about 3 × 10⁹ bp and an early estimate of US $3 per base pair, it would cost about US $9 billion; typed in books of 1000 pages with 1000 letters each, one cell's sequence would fill about 3300 books. Storing, retrieving and analysing such data drove the growth of bioinformatics.
| Goals of the HGP (NCERT) | |
|---|---|
| 1 | Identify all the approximately 20,000–25,000 genes in human DNA |
| 2 | Determine the sequence of the 3 billion chemical base pairs |
| 3 | Store the information in databases |
| 4 | Improve tools for data analysis |
| 5 | Transfer related technologies to other sectors such as industry |
| 6 | Address the ethical, legal and social issues (ELSI) the project may raise |
It was a 13-year project coordinated by the US Department of Energy and the National Institutes of Health, with the Wellcome Trust (UK) a major partner and contributions from Japan, France, Germany, China and others; it was completed in 2003. Knowing how DNA varies between people could transform diagnosis, treatment and prevention of disorders. Genomes of non-human model organisms — bacteria, yeast, Caenorhabditis elegans (a free-living nematode), Drosophila, rice and Arabidopsis — have also been sequenced, with uses in health care, agriculture, energy and environmental remediation.
Methods. One approach identified all genes expressed as RNA — Expressed Sequence Tags (ESTs). The other sequenced the whole genome, coding and non-coding, and assigned functions later — sequence annotation. Total DNA was broken into random small fragments, cloned in hosts (bacteria, yeast) using vectors called BAC (bacterial artificial chromosome) and YAC (yeast artificial chromosome) to amplify them, and sequenced on automated sequencers based on Frederick Sanger's method (Sanger also developed protein sequencing). Overlapping fragments were aligned by computer, annotated and assigned to chromosomes; the last, chromosome 1, was completed in May 2006 (of 24: 22 autosomes, X and Y). Genetic and physical maps used polymorphism in restriction-enzyme sites and repetitive DNA called microsatellites.
| Salient feature (NCERT 5.9.1) | Figure |
|---|---|
| Size of the human genome | 3164.7 million bp |
| Average gene / largest known gene | 3,000 bases / dystrophin, 2.4 million bases |
| Total genes (estimate) | 30,000 — far below earlier estimates of 80,000–1,40,000 |
| Bases identical in all humans | 99.9 per cent |
| Genes of unknown function | over 50 per cent |
| Genome coding for proteins | less than 2 per cent; repeated sequences make up a very large part |
| Most / fewest genes | chromosome 1 (2968) / Y (231) |
| Single-base differences (SNPs, ‘snips’) | about 1.4 million locations |
Applications. Whole-genome sequences and high-throughput methods let researchers study all genes, all the transcripts of a tissue, organ or tumour, or how thousands of genes and proteins work in networks — instead of one gene at a time. Repetitive sequences have no direct coding function but shed light on chromosome structure, dynamics and evolution; SNPs help locate disease-associated sequences and trace human history.
| Position on genomic data and genetic privacy (attributed) | What it argues |
|---|---|
| Genome researchers and public genome projects | open, shared genome data speed discovery of disease genes and drugs; large, diverse datasets are needed so populations such as India's are not left out |
| Privacy and civil-liberties advocates | genomes are uniquely identifying and reveal relatives' information too; even ‘anonymised’ data can be re-identified, so consent and strict limits on use and sharing are essential |
| Patients' groups and bioethicists | genetic results must not lead to discrimination in jobs, insurance or marriage; testing should come with counselling |
| Community and indigenous groups | communities whose samples are used should give collective consent and share in the benefits, rather than see data and profits flow elsewhere |
- HGP: 1990–2003, 13 years, led by the US DoE and NIH; the Wellcome Trust was the main other partner. Chromosome 1 was finished last, in 2006.
- NCERT inconsistency on gene number: the goals say 20,000–25,000 genes, the salient features ‘30,000’. Quote ‘about 30,000 (NCERT)’ if asked from the book; current estimates are about 20,000 protein-coding genes (Beyond NCERT).
- Genome size appears as 3 × 10⁹ (goals), 3.3 × 10⁹ (haploid, page 80) and 3164.7 million bp (features) — the same quantity, rounded differently.
- ESTs = expressed genes; annotation = assigning function after whole-genome sequencing. BAC/YAC = vectors; Sanger = sequencing method.
- Less than 2% codes for protein; 99.9% identical between people; 1.4 million SNPs; chromosome 1 most genes, Y fewest.
- A ‘working draft’ of the human genome was announced in 2001; the remaining gaps were closed by the Telomere-to-Telomere consortium, which published a truly complete sequence in 2022.
- Yeast (Saccharomyces cerevisiae) was the first eukaryote whose whole genome was sequenced, in 1996 (UPSC 1997).
- GenomeIndia, funded by the Department of Biotechnology (DBT), aims to build a catalogue of genetic variation of the Indian population by sequencing about 10,000 genomes from across the country; it is a national project, not part of the international HGP (UPSC 2026).
- The transcriptome is the full set of RNA (mRNA) molecules expressed by a cell, tissue or organism at a time; the proteome is the full set of proteins.
10. DNA fingerprinting
If 99.9 per cent of bases are the same in all humans, then in a genome of 3 × 10⁹ bp about 3 × 10⁶ bases differ (NCERT's in-text question). Sequencing everyone's DNA to find them would be slow and costly; DNA fingerprinting compares individuals quickly. It targets repetitive DNA, in which a short stretch is repeated many times. In density-gradient centrifugation bulk DNA forms a major peak and repetitive DNA forms small peaks — satellite DNA, classed by base composition (A:T- or G:C-rich), segment length and number of repeats into micro-satellites, mini-satellites and so on. These normally code for no protein, form a large part of the genome, and are highly polymorphic. DNA from any tissue of a person — blood, hair follicle, skin, bone, saliva, sperm — shows the same pattern, which makes it a forensic tool; and because polymorphisms are inherited, it is the basis of paternity testing.
Polymorphism (variation at the genetic level) arises from mutation in somatic or germ cells. A germ-line mutation that does not seriously impair reproduction can spread through a population. An allelic variant is traditionally called a DNA polymorphism if more than one variant at a locus occurs with a frequency greater than 0.01. Mutations in non-coding DNA are more likely to persist, since they may have no immediate effect on reproduction, so variation accumulates there over generations — from single-nucleotide changes to large-scale ones — and matters for evolution and speciation.
The technique was developed by Alec Jeffreys, using as probe a highly polymorphic satellite DNA called VNTR (Variable Number of Tandem Repeats), a mini-satellite: a short sequence repeated in tandem, its copy number differing between chromosomes and individuals, so the VNTR ranges in size from 0.1 to 20 kb. After hybridisation with the VNTR probe the autoradiogram shows many bands of different sizes, a pattern characteristic of an individual and different for everyone except monozygotic (identical) twins. PCR (Chapter 9) has raised sensitivity so that DNA from a single cell is enough. Besides forensics, fingerprinting is used to study population and genetic diversity; many probes are now used.
| Use | What is compared |
|---|---|
| Forensics (crime scenes) | bands from trace evidence (hair, saliva, semen, blood) against suspects' bands |
| Paternity and maternity disputes | every band of the child must come from one parent or the other |
| Identifying remains, disaster victims | bands of remains against relatives |
| Population and genetic diversity, evolution | how often band variants occur in different populations or species (UPSC 2023: microsatellites) |
| Position on forensic DNA databases (attributed) | What it argues |
|---|---|
| Police and forensic agencies | a national DNA database speeds identification of offenders, missing persons and unidentified bodies, and can clear the wrongly accused |
| Privacy and civil-liberties groups | storing profiles of suspects, undertrials or relatives risks surveillance and misuse; the Supreme Court recognised privacy as a fundamental right in Justice K.S. Puttaswamy v. Union of India (2017) |
| Forensic scientists and defence lawyers | a match is a statistical statement; contamination, mixed samples and lab quality need accreditation and independent review |
| Parliamentary and legal scrutiny | safeguards — consent, deletion of profiles, oversight bodies — must be written into law before databases expand |
- Repetitive DNA = any repeated sequence; satellite DNA = repetitive DNA that separates as small peaks in density-gradient centrifugation (exercise 8a). VNTRs are mini-satellites; microsatellites are shorter repeats.
- Fingerprinting uses non-coding, highly polymorphic DNA — not genes.
- Polymorphism = variant with frequency above 0.01 in a population; it arises by mutation.
- Identical (monozygotic) twins have the same fingerprint; fraternal twins do not.
- Order of steps: isolate → digest → electrophoresis → blot → hybridise → autoradiograph. Southern blotting is for DNA.
- NCERT slip: page 105 says ‘compare two sets of 3 × 10⁶ base pairs’; it should be 3 × 10⁹ (the genome) — 3 × 10⁶ is the number of differences.
- DNA fingerprinting (an individual) ≠ DNA barcoding (identifying a species from a short standard gene region, Beyond NCERT).
- Alec Jeffreys developed the method at the University of Leicester in 1984. Modern forensic profiles use PCR-amplified short tandem repeats (STRs), a kind of microsatellite.
- India's Centre for DNA Fingerprinting and Diagnostics (CDFD) is in Hyderabad (UPSC 2001, 2008).
- Under Section 112 of the Indian Evidence Act, 1872, a child born during a valid marriage is presumed legitimate; courts have weighed DNA tests against this presumption and the right to privacy (UPSC Mains 2024).
NCERT's in-text questions — short answers
The chapter asks many questions in the running text. Short outlines follow, in page order.
Page 82: Compare the structure of purines and pyrimidines. Can you find out why the distance between two polynucleotide chains in DNA remains almost constant?
Page 83: In some viruses the flow of information is from RNA to DNA. Can you suggest a simple name to the process?
Page 83: If the length of E. coli DNA is 1.36 mm, can you calculate the number of base pairs in E. coli?
Page 83: Theoretically, how many such beads (nucleosomes) do you imagine are present in a mammalian cell?
Page 85: Can you think of any difference between DNAs and DNase?
Page 87: Can you recall the two chemical differences between DNA and RNA?
Page 89: Can you recall what centrifugal force is, and think why a molecule with higher mass/density would sediment faster?
Page 90: If E. coli was allowed to grow for 80 minutes then what would be the proportions of light and hybrid densities DNA molecule?
Page 92: Can you now write the sequence of RNA transcribed from the above DNA?
Page 96: If following is the sequence of nucleotides in mRNA, predict the sequence of amino acid coded by it: -AUG UUU UUC UUC UUU UUU UUC-
Page 97: Now try the opposite. Met-Phe-Phe-Phe-Phe-Phe-Phe: predict the nucleotide sequence in the RNA. Do you face any difficulty? Which two properties of the genetic code have you learnt?
Page 101: Can you think for how long the lac operon would be expressed in the presence of lactose?
Page 105: Assuming human genome as 3 × 10⁹ bp, in how many base sequences would there be differences?
NCERT exercise — answer outlines
Try each question first, then open the outline. For sequences, write the 5′ and 3′ ends every time.
1. Group the following as nitrogenous bases and nucleosides: Adenine, Cytidine, Thymine, Guanosine, Uracil and Cytosine.
2. If a double stranded DNA has 20 per cent of cytosine, calculate the per cent of adenine in the DNA.
3. If the sequence of one strand of DNA is written as follows: 5'-ATGCATGCATGCATGCATGCATGCATGC-3'. Write down the sequence of complementary strand in 5'→3' direction.
4. If the sequence of the coding strand in a transcription unit is written as follows: 5'-ATGCATGCATGCATGCATGCATGCATGC-3'. Write down the sequence of mRNA.
5. Which property of DNA double helix led Watson and Crick to hypothesise semi-conservative mode of DNA replication? Explain.
6. Depending upon the chemical nature of the template (DNA or RNA) and the nature of nucleic acids synthesised from it (DNA or RNA), list the types of nucleic acid polymerases.
7. How did Hershey and Chase differentiate between DNA and protein in their experiment while proving that DNA is the genetic material?
8. Differentiate between the followings: (a) Repetitive DNA and Satellite DNA (b) mRNA and tRNA (c) Template strand and Coding strand
9. List two essential roles of ribosome during translation.
10. In the medium where E. coli was growing, lactose was added, which induced the lac operon. Then, why does lac operon shut down some time after addition of lactose in the medium?
11. Explain (in one or two lines) the function of the followings: (a) Promoter (b) tRNA (c) Exons
12. Why is the Human Genome Project called a mega project?
13. What is DNA fingerprinting? Mention its application.
14. Briefly describe the following: (a) Transcription (b) Polymorphism (c) Translation (d) Bioinformatics
What to remember
Numbers
One-liners
- Chargaff: in double-stranded DNA A = T and G = C.
- A purine always pairs with a pyrimidine, keeping the helix width constant.
- Histones are positively charged because they are rich in lysine and arginine.
- Griffith found transformation; Avery's team showed it was DNA; Hershey and Chase proved it.
- ³²P labels DNA; ³⁵S labels protein.
- DNA is better for storing information, RNA for transmitting it.
- Replication is semiconservative — proved with ¹⁵N and CsCl centrifugation.
- DNA polymerase works only 5′→3′, so one new strand is discontinuous and joined by ligase.
- The template strand is read 3′→5′; the coding strand has the RNA's sequence.
- σ starts and ρ stops bacterial transcription.
- Eukaryotic hnRNA is capped, tailed and spliced to give mRNA.
- The code is triplet, degenerate, comma-less and nearly universal.
- tRNA is the adapter; there are no tRNAs for stop codons.
- The peptide bond is made by rRNA — a ribozyme.
- The lac repressor binds the operator; lactose is the inducer.
- DNA fingerprinting uses VNTRs; only identical twins share a pattern.
Traps to avoid
- Chargaff's rule does not mean A + T = G + C, and it does not hold within one strand.
- ³²P went into the bacteria; ³⁵S stayed outside in the supernatant.
- ¹⁵N is not radioactive; it is separated by density.
- The coding strand is not read; the template strand is.
- 5S rRNA is made by RNA polymerase III, not I.
- Frame-shift = insertion or deletion of one or two bases; three bases keep the frame.
- AUG codes for methionine and is also the start codon.
- The i gene's name comes from inhibitor, not inducer.
- Glucose and galactose cannot induce the lac operon.
- NCERT gives the human gene number as both 20,000–25,000 and 30,000.
- ‘3 × 10⁶ base pairs’ on page 105 should be 3 × 10⁹; 3 × 10⁶ is the number of differences.
- DNA fingerprinting identifies individuals; DNA barcoding identifies species.
How to strategise
Prelims — what UPSC asks
- Core molecular biology: tRNA is the adapter that translates the code (1985); base pairs are A–T and C–G (1985); genes act through protein synthesis (1986); complementarity of the two strands is what suits DNA to store and pass on information (2001); Jacob and Monod gave the operon concept (1998, a match with de Vries, Darwin and Beadle–Tatum); and the genetics pioneers match — Lederberg, Morgan, Kornberg, Khorana (2001); James Watson worked in genetics (2008).
- Genomes and fingerprints: DNA fingerprinting solves crimes (1991), establishes paternity (1997) and works on trace hair, saliva and semen (2000); yeast was the genome completed in 1996 (1997); genome sequencing helps crops — markers, faster breeding, host–pathogen studies (2017); the transcriptome is the full range of mRNA (2016); microsatellite DNA studies evolutionary relationships (2023); GenomeIndia is DBT-funded and catalogues Indian genetic diversity, but is not part of the HGP (2026); and viruses do infect bacteria and change host transcription (2025, none of the three statements correct).
- Key notes: 1985 ‘genetic code is made up by the four letter alphabet forming the pairs’ is loosely worded — the code is read as triplet codons, not pairs; the keyed answer (d) A–T, T–A, C–G, G–C is right as the base-pairing rule. 2001 genetics match: the key (d) stands — Lederberg (conjugation, transduction), Morgan (sex-linkage), Kornberg (DNA polymerase), Khorana (genetic code); Ochoa is the distractor though he also contributed. 1997 yeast is Beyond NCERT as a date — the weakest link kept.
- Likely next: Chargaff arithmetic, template vs coding strand, RNA polymerase I/II/III, codon properties, lac operon genes, HGP numbers, SNPs, VNTR vs STR, DNA barcoding vs fingerprinting, RNA vaccines and RNAi (built on transcription and translation), and genome-editing news.
Mains — where it appears and how to answer
- GS2 2024 asked about the right to privacy under Article 21 and the law on DNA testing of a child in the womb to establish paternity; Section 10 supplies the science — what a DNA profile is, why every band of a child must come from a parent, and why one cell suffices with PCR. The legal half needs the polity chapters.
- Use this chapter as the science base for GS3 answers on genome sequencing (GenomeIndia, precision medicine, pathogen surveillance), biotechnology in agriculture and health, and forensic DNA. Frame: one line of molecular biology → application → Indian programme or institution (DBT, CDFD) → attributed concerns (privacy, consent, discrimination, lab quality) → way forward.
- A two-line base-pairing or codon example can make a technical point quickly; keep claims about laws and bills dated and attributed.
Self-check
Tap an option. NCERT's own exercise questions come first; the rest test the figures and common confusions.
1. A double-stranded DNA has 20% cytosine. What percentage of its bases is adenine?
2. In the Hershey–Chase experiment, radioactivity was found inside the bacteria when the phages had been grown with:
3. E. coli grown for many generations in ¹⁵N is moved to ¹⁴N. After 80 minutes (four generations), the DNA is:
4. The coding strand of a gene reads 5′-ATGCAT-3′. The mRNA transcribed from this gene reads:
5. Which RNA polymerase transcribes tRNA and 5S rRNA in eukaryotes?
6. Inserting two bases into the middle of a gene most likely causes:
7. In the lac operon, the repressor protein is coded by the:
8. DNA fingerprinting depends mainly on:
UPSC questions from this chapter
Open any question to attempt it in the Question bank — your attempt is saved to your progress.