Chromosomes, genes and alleles: the two-metre instruction book folded into every nucleus
By the end of this lesson you will be able to
- Label a zoom diagram from cell to nucleus to chromosome to DNA to gene to nucleotide, and state what each level is made of.
- Describe the structure of DNA — two sugar-phosphate backbones, complementary base pairs A–T and C–G — and explain why a gene is “a section of DNA that codes for a protein”.
- State that human body cells carry 46 chromosomes in 23 homologous pairs, including one pair of sex chromosomes, and interpret a karyotype.
- Define locus, allele, homozygous and heterozygous, and use them correctly for a named gene.
- Calculate with genome data — base pairs, genes, lengths in scientific notation — and evaluate the claim that a bigger genome means a more complex organism.
You met this before
- Animal and plant cells have a nucleus (bacteria do not; nor do a few specialised cells such as mature red blood cells); the nucleus controls the cell and holds its DNA, packed into chromosomes — 46 in a human body cell.
- Cells divide by mitosis for growth and repair: the DNA is copied first, so each daughter cell gets a complete set of 46.
- Gametes — sperm and egg — carry 23 chromosomes; fertilisation restores 46 in the zygote.
- Variation between individuals is genetic, environmental or both: discontinuous traits fall into categories (bar chart), continuous traits form a range (histogram).
- Prefixes you will need: kilo (10³), mega (10⁶), giga (10⁹); micro (10⁻⁶), nano (10⁻⁹). A nucleus is about 6 μm across; a DNA molecule is 2 nm wide.
A cheek cell has 46 chromosomes. Write down how many a sperm has, how many a zygote has, and how many each daughter cell has after the zygote divides by mitosis.
Reveal
Sperm 23; zygote 23 + 23 = 46; each daughter cell 46, because mitosis copies every chromosome before the split. Only the making of gametes halves the number — that is Lesson 2.
Revise it in full: Year 1 · Cell structure · Lesson 2 — Inside the cell · Year 2 · Cell functions · Lesson 2 — Cells dividing · Year 3 · Variation · Lesson 3 — Why no two mopane leaves are the same
The puzzle
Take one cell from the lining of your cheek — about 60 μm across, invisible without a microscope. Inside its nucleus, 6 μm wide, is a thread that, if you could pull it out and lay it straight, would be about two metres long: longer than you are tall, thinner than any wire ever made, and carrying the complete instructions for building and running a human being.
Every one of your roughly 37 trillion cells has its own copy. How do you fit two metres into six millionths of a metre — and how does a cell read a book that is folded ten thousand times?
Before reading on, predict: (i) how many times shorter than its stretched-out DNA a chromosome must be; (ii) whether a wheat plant, with five times as much DNA per cell as you, has five times as many genes.
Compare your answer
(i) Roughly ten thousand times. Chromosome 1 holds about 8.4 cm of DNA and is about 10 μm long when it is visible under a microscope: 0.084 m ÷ 1 × 10⁻⁵ m ≈ 8 400.
(ii) No. Bread wheat has about 16 billion base pairs to your 3.1 billion, but most of that is repeated sequence that codes for nothing; gene number does not track genome size at all, which is the puzzle biologists call the C-value paradox. You will work through the numbers in Section 1.5.
The science — structured notes
1.1 The zoom: from cell to nucleotide
Genetics is a story told at five scales, and the examination’s favourite Criterion A item is a diagram that zooms through them and asks you to drag five labels into place. Learn the order as a chain, each level made of the next.
| Level | What it is | Size and number in a human body cell |
|---|---|---|
| Nucleus | The organelle that holds the chromosomes and controls the cell | About 6 μm across; one per cell (none in a mature red blood cell) |
| Chromosome | One very long DNA molecule wound round proteins (histones) and supercoiled; visible only when a cell divides | 46, in 23 pairs; from 47 million to 248 million base pairs each |
| DNA | Deoxyribonucleic acid — a double helix of two strands held together by paired bases | 2 nm wide; 6.2 × 10⁹ base pairs in total, about 2 m long if stretched |
| Gene | A section of DNA whose sequence of bases codes for one protein (or part of one) | About 20 000 protein-coding genes; typically 10 000–100 000 base pairs each including non-coding parts |
| Nucleotide | One unit of a DNA strand: a phosphate, a deoxyribose sugar and one of four bases (A, T, C, G) | 0.34 nm from one to the next along the strand |
1.2 DNA: two backbones and a code of four letters
A DNA molecule is two strands running in opposite directions and twisted into a double helix. Each strand is a chain of nucleotides; the phosphate of one joins the sugar of the next, so the outside of the helix is a repeating sugar-phosphate backbone.
The bases point inwards and pair across the middle: adenine (A) always pairs with thymine (T), and cytosine (C) always pairs with guanine (G). A pairs with T through two hydrogen bonds, C with G through three, and the shapes fit only in these combinations — a purine (A or G, two rings) opposite a pyrimidine (T or C, one ring) keeps the helix a constant 2 nm wide.
This is complementary base pairing, and it is the reason DNA can be copied: pull the strands apart and each one dictates the other.
The order of bases along one strand is the genetic code. A gene is a section of DNA — hundreds to thousands of bases — whose base sequence specifies the order of amino acids in one protein; the cell reads it three bases at a time, each triplet standing for one amino acid.
Proteins are the enzymes, structural fibres, transport molecules and receptors that make a cell what it is, so “which proteins are made” becomes “which traits appear”: the eye pigment, the shape of a red blood cell, the enzyme that digests lactose.
Most of the genome does not code for protein at all — about 1 % of your 3.1 billion base pairs is protein-coding; much of the rest controls when and where genes are switched on, and a great deal is repeated sequence with no known job.
One strand of a short DNA section reads A T G C C G T A A G. (1) Write the complementary strand. (2) A DNA molecule is found to be 24 % adenine. Calculate the percentage of each of the other three bases.
(1) Pair every base: A→T, T→A, G→C, C→G. Complementary strand: T A C G G C A T T C. Check it has the same length, 10 bases, and that A and T counts match across the pair (A: 3 on the first strand, 3 T on the second ✓).
(2) Every A on one strand faces a T on the other, so across the whole molecule A = T: T = 24 %.
What is left is 100 − 24 − 24 = 52 %, shared equally between C and G because every C faces a G.
C = 26 %
G = 26 %
This equality (A = T, C = G) is Chargaff’s rule, measured in 1950 and one of the two clues that gave Watson and Crick the structure.
1.3 Chromosomes: 46 = 23 pairs, and one pair decides sex
Between divisions the DNA in a nucleus is loosely spread out so that genes can be read. When a cell prepares to divide it winds each DNA molecule tightly round histone proteins and coils the coils — supercoiling — until each molecule becomes a rod-shaped chromosome short enough to be moved without tangling.
A chromosome is therefore not something separate from DNA: it is one DNA molecule packed about ten thousand times shorter than its own length.
A human body cell has 46 chromosomes in 23 pairs. One chromosome of every pair came from the mother in the egg and one from the father in the sperm.
The two members of a pair are the same length, have the same banding pattern and carry the same genes in the same order; they are called homologous chromosomes.
Twenty-two of the pairs, the autosomes, are numbered 1 to 22 from largest to smallest. The twenty-third pair is the sex chromosomes: a female has two X chromosomes (XX), a male has an X and a much smaller Y (XY).
The Y carries only a few dozen protein-coding genes against the X’s roughly 800, but one of them — SRY — switches on the development of testes, and Lesson 4 shows why that makes the sperm, not the egg, the deciding gamete.
A karyotype is the set of chromosomes of one cell, photographed at the moment of division and arranged in pairs by size. Laboratories make one from a blood sample: white blood cells are grown for a few days, treated with colchicine so that dividing cells stop with their chromosomes at their most condensed, burst on a slide, stained, and photographed.
Reading one takes two questions — how many, and which sex pair — and it detects a missing or extra whole chromosome, though not a single changed base.
| Species | Chromosomes per body cell | Pairs | Worth noticing |
|---|---|---|---|
| Human | 46 | 23 | Chromosome 2 is two ape chromosomes fused end to end |
| Chimpanzee | 48 | 24 | The extra pair is the unfused version of our chromosome 2 |
| Dog | 78 | 39 | More chromosomes than a human, no more genes |
| Cattle and goat | 60 | 30 | The same count does not mean the same genes |
| Horse / donkey / mule | 64 / 62 / 63 | 32 / 31 / — | A mule’s odd number cannot form pairs, so it is sterile (Lesson 2) |
| Garden pea | 14 | 7 | Mendel’s seven traits happen to sit on separate pairs or far apart |
| Onion | 16 | 8 | Large chromosomes — the classroom root-tip squash |
| Fruit fly | 8 | 4 | Morgan’s 1910 white-eyed fly put a gene on the X |
| Adder’s-tongue fern | about 1 260 | about 630 | The record; number says nothing about complexity |
“A karyotype can show whether a baby will have cystic fibrosis.”
Reveal answer
False. A karyotype shows the number and shape of whole chromosomes: it will reveal an extra chromosome 21 (Down syndrome) or the sex chromosomes, because those are changes of millions of base pairs.
Cystic fibrosis is caused by a change of a few bases within one gene on chromosome 7 — the commonest form deletes just three nucleotides — and a chromosome with three bases missing looks identical under a microscope. Detecting it needs the DNA sequence itself (Lesson 5).
1.4 Locus and allele: the same page, a different spelling
Every gene has a fixed address: a particular position on a particular chromosome, called its locus (plural loci). The gene for the ABO blood group is at one locus on chromosome 9; the gene whose fault causes cystic fibrosis is at one locus on chromosome 7. Because your chromosomes come in homologous pairs, you carry two copies of every gene on the autosomes — one at the same locus on each chromosome of the pair.
The two copies need not be spelled the same. A gene’s DNA sequence can exist in slightly different versions, differing by one or a few bases; each version is an allele.
Alleles of a gene occupy the same locus on homologous chromosomes and control the same trait, but they may produce different forms of the protein and so different versions of the trait.
If the two alleles you carry are identical you are homozygous for that gene; if they are different you are heterozygous. The pair of alleles you carry is your genotype for the gene; the trait you show is your phenotype.
Lesson 3 does the arithmetic of what happens when parents pass one allele each to a child; for now the four words must be exact.
| Term | Exact definition | Example with the lactase gene (Lesson 3 and 4) |
|---|---|---|
| Gene | A section of DNA that codes for a protein and so specifies a trait | The gene controlling whether lactase is still made in adults |
| Locus | The fixed position of a gene on a chromosome | On chromosome 2 |
| Allele | One of the alternative forms of a gene, at the same locus, differing in base sequence | T (lactase persists) and t (lactase switched off after childhood) |
| Homozygous | Both alleles at a locus identical | TT or tt |
| Heterozygous | The two alleles at a locus different | Tt |
| Genotype | The alleles an individual carries for a gene | Tt |
| Phenotype | The observable trait that results | Lactose tolerant |
A student writes: “The father’s chromosome 7 has the cystic fibrosis gene and the mother’s chromosome 7 does not, so the child is heterozygous.” Rewrite the sentence using locus and allele correctly.
Reveal answer
Both parents have the gene — every human has it, at the same locus on chromosome 7; what differs is the version. “The father’s chromosome 7 carries the faulty allele of the CFTR gene and the mother’s carries the normal allele.
The child inherited one chromosome 7 from each parent, so at that locus the child has one faulty and one normal allele and is heterozygous.” (Whether the child is affected is Lesson 3: the faulty allele is recessive, so a heterozygote is a healthy carrier.)
1.5 Genomes: how much DNA, how many genes, and the paradox
The genome is all the DNA of one set of chromosomes — for a human, the 23 chromosomes of a gamete, about 3.1 × 10⁹ base pairs, plus the small circular chromosome of 16 569 base pairs in every mitochondrion, inherited only from the mother.
Sequencing it means reading the order of all those bases. The Human Genome Project began in 1990 as an international public effort, announced a working draft in June 2000 (published in February 2001) and declared the sequence essentially complete in April 2003 — about 92 % of it, at a cost of roughly three billion US dollars.
The remaining 8 %, mostly highly repeated DNA near the centromeres and chromosome ends, resisted the technology for two more decades; a gapless sequence of one genome was finally published by the Telomere-to-Telomere consortium in 2022.
Then, in May 2023, the Human Pangenome Reference Consortium published a first draft pangenome: the genomes of 47 people of diverse ancestry aligned together, so that the reference is no longer one person’s sequence but a map of the variation between people.
That matters most for Africa, whose populations carry more genetic variation than the rest of the world combined, and whose sequences had been almost absent from the original reference.
| Organism | Genome size / base pairs (haploid) | Protein-coding genes (approx.) | Genes per million base pairs |
|---|---|---|---|
| E. coli bacterium | 4.6 × 10⁶ | 4 300 | 930 |
| Yeast | 1.2 × 10⁷ | 6 000 | 500 |
| Fruit fly | 1.4 × 10⁸ | 14 000 | 100 |
| Rice | 4.3 × 10⁸ | 40 000 | 93 |
| Human | 3.1 × 10⁹ | 20 000 | 6.5 |
| Bread wheat | 1.6 × 10¹⁰ | 100 000 (three ancestral genomes combined) | 6 |
| Australian lungfish | 4.3 × 10¹⁰ | 31 000 | 0.72 |
Two things jump out. Gene number does not scale with genome size: rice has twice your genes in a seventh of the DNA, and the Australian lungfish has fourteen times your DNA with only half as many genes again.
And the fraction of the genome that codes for protein collapses as genomes get larger — 88 % in E. coli, about 1 % in you. Complexity, whatever it is, is not a matter of gene count; it lies in how the same 20 000 genes are switched on and off in different cells at different times, and that regulation is written in the non-coding DNA.
Adjacent base pairs are 0.34 nm apart along the helix. (1) Calculate the total length of DNA in one human body cell. (2) Chromosome 1 has 2.48 × 10⁸ base pairs and is about 10 μm long at the moment of division. Calculate the packing ratio.
(1) A body cell is diploid, so it holds 2 × 3.1 × 10⁹ = 6.2 × 10⁹ base pairs.
Length = 6.2 × 10⁹ × 0.34 × 10⁻⁹ m = 2.1 m
Convert the nanometres before multiplying — a common slip gives 2.1 × 10⁹ m, more than five times the distance from the Earth to the Moon, which a quick sense check rejects.
(2) Length of the DNA = number of base pairs × 0.34 nm
Length = 2.48 × 10⁸ × 0.34 × 10⁻⁹ m
Length = 8.4 × 10⁻² m = 8.4 cm
Packing ratio = 8.4 × 10⁻² m1.0 × 10⁻⁵ m = 8 400, no unit because it is a length divided by a length. Supercoiling makes the molecule about eight thousand times shorter — which is why “chromosomes are structures of supercoiled DNA” is the IB’s own phrase.
A newly sequenced fish has a genome of 9.0 × 10⁸ base pairs on 24 pairs of chromosomes and 22 000 protein-coding genes. Its average gene, including non-coding sections, spans 2.5 × 10⁴ base pairs. (1) Estimate the mean number of genes per chromosome and the mean base pairs per chromosome. (2) Estimate the fraction of the genome inside genes, and comment on what the rest might be.
(1) Genes per chromosome = 22 000 ÷ 24 ≈ 920.
Base pairs per chromosome = 9.0 × 10⁸ ÷ 24 = 3.8 × 10⁷. (These are means — real chromosomes differ several-fold in size.)
(2) DNA inside genes = 22 000 × 2.5 × 10⁴ = 5.5 × 10⁸ base pairs
Fraction of the genome = 5.5 × 10⁸ ÷ 9.0 × 10⁸ = 0.61, or 61 %
The remaining 39 % lies between genes: regulatory sequences that switch genes on and off, repeated sequences, and the centromere and telomere regions that hold chromosomes together and protect their ends.
Note that “inside genes” is not “coding”: most of a gene’s span is non-coding too, so the protein-coding fraction would be far smaller.
The mitochondrial genome is 16 569 base pairs and carries 37 genes; the nuclear genome is 3.1 × 10⁹ base pairs with 20 000 genes.
(a) Calculate the genes per million base pairs for each, to 2 significant figures.
(b) Calculate the stretched length of one mitochondrial DNA molecule.
(c) A cell has about 1 000 mitochondria, each with several copies of the circle. Explain why a DNA test on a hair shaft with no root, which contains almost no nuclear DNA, can still identify a person’s mother’s family line.
Reveal answer
(a) Mitochondrial: 37 ÷ 0.016569 = 2 200 genes per million base pairs. Nuclear: 20 000 ÷ 3 100 = 6.5. The mitochondrial circle is packed like a bacterial genome — which is what it once was.
(b) 16 569 × 0.34 × 10⁻⁹ m = 5.6 × 10⁻⁶ m = 5.6 μm — about the diameter of the nucleus, for a molecule that lives in an organelle 1 μm across, so it too must be coiled.
(c) Each cell has one nucleus but hundreds of mitochondria with several DNA circles each, so there are thousands of copies of mitochondrial DNA per cell and a degraded sample still yields some intact copies; mitochondria are inherited only through the egg, so the sequence is the same as the mother’s, her mother’s and so on, which identifies the maternal line — but not the individual, since every sibling shares it.
Explain why a person’s skin cells, liver cells and nerve cells contain the same 46 chromosomes and the same alleles, yet look and behave completely differently.
Reveal answer
All three cell types descend from the one zygote by mitosis, which copies every chromosome exactly, so every body cell has the same DNA sequence and the same alleles at every locus.
The cells differ because different genes are switched on: a skin cell reads the genes for keratin and switches off the genes for liver enzymes, a nerve cell reads the genes for the proteins that carry electrical signals.
Which genes are read is controlled by regulatory DNA outside the coding sequences and by signals the cell received as the embryo developed. Same book, different pages open.
A student says “chimpanzees have 48 chromosomes and humans 46, so chimpanzees have about 4 % more genes.” Use the table in 1.3 and the idea of chromosome fusion to explain what is wrong with the reasoning.
Reveal answer
Chromosome number counts the packets, not the contents. Human chromosome 2 is the end-to-end fusion of two ancestral ape chromosomes that chimpanzees still carry separately — the same genes, distributed over 24 pairs in the chimpanzee and 23 in us, with the fused chromosome carrying the remains of a second centromere and internal telomere sequences as evidence.
Both species have roughly 20 000 protein-coding genes; a dog with 78 chromosomes has no more. Gene number depends on the DNA sequence, not on how many rods it is cut into.
A DNA sample is 30 % guanine. It is claimed to come from a single-stranded DNA virus. Explain whether the base composition alone can support or refute the claim, and what further measurement would settle it.
Reveal answer
Base composition alone cannot decide it.
In double-stranded DNA the pairing rule forces G = C and A = T, so 30 % G would require 30 % C and 20 % each of A and T.
If the measured C is also 30 %, the sample is consistent with double-stranded DNA but not proved to be, because a single strand could by coincidence have equal G and C.
If the measured C is not 30 % — say G = 30 %, C = 18 % — the pairing rule is broken and the DNA must be single-stranded, which would support the claim.
So the further measurement is the percentage of cytosine (and of A against T): equality is compatible with either, inequality proves single strands.
Try it — build the scale in your hands
No virtual lab fits this lesson, because its content is structure rather than a measurable relationship; the exercise below makes the numbers physical instead. You need 2 m of cotton thread, a small bead about 6 mm across, a ruler and a calculator. The model is built at a scale of one thousand to one: the bead is the nucleus at that scale, and the thread stands for a short stretch of its DNA.
Suppose your Step 2 bundle was 4.0 cm across and your Step 3 supercoil was 12 cm long.
(a) Calculate both packing ratios and explain why coiling beats stuffing.
(b) Explain why a cell keeps its DNA supercoiled only while it divides and unpacks it the rest of the time.
Reveal answer
(a) Stuffed: 200 cm ÷ 4.0 cm = 50. Supercoiled: 200 cm ÷ 12 cm = 17 in length, but the coil is a tidy rod that can be moved without tangling, while the stuffed bundle is a knot that cannot be pulled apart without breaking the thread.
The cell needs both compactness and orderliness, because at division two copies of each molecule must be separated cleanly; hierarchical coiling gives an 8 000-fold shortening and lets the two copies be pulled apart.
(b) Genes can only be read when enzymes can reach the bases, and copying the whole molecule before division needs the strands opened along their whole length; a supercoiled chromosome is closed for reading. So the cell spreads the DNA out between divisions, when it is working and copying, and condenses it only for the hour or two when it must be transported into two daughter cells without breaking.
Explore it live
Try it: Slide the zoom from a whole cheek cell down to single bases, and change the two alleles to see what homozygous and heterozygous look like at each level.
Common mistakes to avoid
- Swapping the levels — a chromosome is made of DNA; a gene is a section of DNA; a nucleotide is one unit of DNA. Chromosomes are not “inside genes”.
- “Genes for” a disease — everyone has the gene; the difference is the allele. Write “the faulty allele of the CFTR gene”.
- A single letter for a genotype — the May 2021 markscheme refused “d” for the mother’s genotype; body cells carry two alleles, so write dd.
- Homologous means identical — same genes, same loci, possibly different alleles.
- “23 chromosomes” for a body cell — 23 pairs, 46 chromosomes; gametes have 23.
- More DNA or more chromosomes means more genes or more complexity — wheat, lungfish and dogs all contradict it.
- Nanometre slips — convert 0.34 nm to 0.34 × 10⁻⁹ m before multiplying, and check that the answer is a sensible size.
Study smart: how this is examined
Study routine. Today: draw the zoom diagram from memory, then the karyotype in words (22 pairs + XX or XY), and write the seven definitions of Section 1.4 on one card.
In two days: cover the card and rewrite the definitions; do the two EXAMPLE calculations with the book closed. In a week: take the quiz for this lesson, then explain to someone else why a gene, a chromosome and DNA are one thing at three magnifications.
How we found out — from pus-soaked bandages to a photograph
In 1869 Friedrich Miescher, a young Swiss chemist working in Tübingen, extracted a phosphorus-rich substance from the nuclei of white blood cells collected from used surgical bandages. He called it “nuclein”; nobody, including Miescher, thought it could carry inheritance, because a molecule with only four kinds of unit seemed too simple.
Proteins, with twenty amino acids, looked like the better candidate, and that belief held for seventy-five years. Meanwhile the microscopists saw the packaging before anyone understood the contents: Walther Flemming stained dividing salamander cells in 1879, named the threads “chromatin” and in 1882 described mitosis; Wilhelm Waldeyer coined “chromosome” in 1888.
In 1902–1903 Walter Sutton, a graduate student from Kansas working at Columbia University, and Theodor Boveri in Würzburg independently pointed out that chromosomes behaved exactly as Mendel’s hereditary factors should — in pairs, one from each parent, separating when gametes form — and proposed that genes ride on chromosomes. Thomas Hunt Morgan proved it in 1910 with a single white-eyed male fruit fly whose trait travelled with the X chromosome.
The chemistry took longer. Frederick Griffith showed in 1928 that something from dead bacteria could transform living ones; Oswald Avery, Colin MacLeod and Maclyn McCarty purified that something in 1944 and found it was DNA — a result many refused to accept for nearly a decade. Erwin Chargaff measured in 1950 that A equals T and C equals G in every species tested.
In May 1952 Rosalind Franklin, at King’s College London, took an X-ray diffraction photograph of DNA fibres — Photo 51 — whose cross pattern is the signature of a helix, with spacings giving 3.4 nm per turn and 2 nm across.
James Watson and Francis Crick in Cambridge, having seen the photograph and Chargaff’s ratios, built the double-helix model and published it in Nature on 25 April 1953, ending with the most understated sentence in biology: “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” Franklin died of cancer in 1958 at 37.
The Nobel Prize of 1962 went to Watson, Crick and Maurice Wilkins.
Even the human chromosome count was wrong until 1956, when Joe Hin Tjio and Albert Levan, using a better squash technique, counted 46 where textbooks had said 48 for thirty years — and looked back at the old photographs to find 46 had been there all along.
Chargaff’s ratios (A = T, C = G) were published three years before the double helix. Explain what a scientist could and could not conclude from the ratios alone, and why they became decisive once Franklin’s photograph showed a two-stranded helix of constant width.
Reveal answer
Alone, the ratios showed a regularity that any correct model had to explain, but they did not say how: bases might have been paired, or the equality might have arisen some other way.
Franklin’s photograph fixed the geometry — two strands, 2 nm apart, all the way along — and a constant width means each rung must be the same length. A two-ring base opposite a one-ring base gives that constant length; two large or two small bases would not.
Put the two constraints together and only one arrangement survives: A opposite T, G opposite C. That is why the model was accepted quickly once published: it explained the ratios, fitted the diffraction pattern, and offered a copying mechanism as a bonus.
Where it is used now
- Karyotypes in the clinic. A blood karyotype is still the standard first test for a suspected extra or missing chromosome — Down syndrome (an extra 21), Turner syndrome (a single X), Klinefelter syndrome (XXY) — and for the chromosome rearrangements found in some leukaemias, where the test guides the choice of drug.
- African genomes and H3Africa. Human populations in Africa carry more genetic variation than all other continents together, because our species lived there longest; yet by the late 2010s people of African ancestry made up only about 2 % of the individuals in genome-wide studies.
- The Human Heredity and Health in Africa consortium (H3Africa, launched 2012 with NIH and Wellcome funding) built sequencing capacity and biobanks across the continent, and Botswana’s laboratories have contributed studies of HIV in children through the CAfGEN network and, in November 2021, some of the first sequences of the Omicron variant.
- Tracing ivory. DNA extracted from seized tusks is matched against a reference map of elephant genotypes built from dung collected across Africa; the method, developed at the University of Washington, has located the populations being poached and linked separate seizures to the same trafficking networks.
- Identification. DNA profiling compares repeated, highly variable regions of non-coding DNA rather than genes; paternity testing checks that a child’s alleles at each locus can be accounted for by the mother plus the alleged father. The same non-coding repeats identify a body after a disaster.
- Breeding. Cattle and crop breeders now genotype young animals or seedlings and select on the alleles they carry rather than waiting years for the trait to show — the lesson’s vocabulary applied to a sorghum field.
Science now — and the scientist you need to be
What is happening in 2026
Reading a whole human genome cost about three billion dollars and thirteen years for the first one; today a sequencing laboratory reads one in a day for a few hundred dollars, and the bottleneck has moved from reading the letters to understanding them.
That is where artificial intelligence has arrived. AlphaFold, released by DeepMind in 2020–2021, predicts the three-dimensional shape of a protein from its amino-acid sequence (which the gene’s base sequence specifies), and its public database now holds predicted structures for essentially every protein whose gene has been sequenced — over 200 million.
Newer models are trained directly on genome sequences from thousands of species so that, given a stretch of DNA, they can suggest whether a change of one base is likely to be harmless or damaging.
In the clinic that means a child with an undiagnosed condition can have a whole genome read and the likely faulty allele flagged within days, a workflow that hospitals in several countries now run routinely.
The pangenome is growing towards its target of 350 people from every region, so that “the human genome” stops meaning a single reference and starts meaning the map of how humans differ — an idea this unit’s global context, orientation in space and time, was written for.
The mindshift
What you need to be able to do
Three things carry the marks in this lesson. Labelling: the zoom diagram and the karyotype, quickly and completely. Definitions: the seven words of Section 1.4, exact, with “allele” and “gene” never swapped.
Calculation: base pairs to length, percentages of bases, genes per million base pairs, in scientific notation with the unit converted first. The examiners’ reports for biology note that genetics vocabulary is where candidates “contradict themselves” — a definition that uses the wrong word scores zero even when the idea is right.
See an example
Maize 20 chromosomes, 2.3 × 10⁹ base pairs; domestic cat 38, 2.5 × 10⁹; E. coli in my gut, 1 chromosome, 4.6 × 10⁶. The assistant’s first answer said “the gene for cystic fibrosis”; when asked whether everyone has that gene it corrected itself to “the faulty allele of the CFTR gene, which everyone has at the same locus on chromosome 7”.
Key terms
| Nucleus | The organelle that contains the chromosomes and controls the cell. |
| Chromosome | A structure of supercoiled DNA (wound on histone proteins) carrying genes in a fixed order; 46 in a human body cell, in 23 homologous pairs. |
| DNA | Deoxyribonucleic acid: two strands of nucleotides in a double helix, held by complementary base pairs A–T and C–G. |
| Nucleotide | One unit of DNA: a phosphate, a deoxyribose sugar and a base (A, T, C or G). |
| Gene | A section of DNA that codes for a protein and so specifies a trait; passed from parent to offspring. |
| Locus | The fixed position of a gene on a chromosome. |
| Allele | One of the alternative forms of a gene, at the same locus on homologous chromosomes. |
| Homologous chromosomes | A pair of chromosomes, one from each parent, with the same genes at the same loci. |
| Homozygous / heterozygous | Two identical alleles at a locus / two different alleles at a locus. |
| Genotype / phenotype | The alleles an individual carries / the observable trait that results. |
| Karyotype | The full set of chromosomes of one cell, photographed at division and arranged in pairs by size. |
| Sex chromosomes | The 23rd pair: XX in a female, XY in a male; the other 22 pairs are autosomes. |
| Genome | All the DNA of one set of chromosomes: about 3.1 × 10⁹ base pairs and 20 000 protein-coding genes in a human. |
Think like a scientist
Criterion C A research group compared genome size with the number of protein-coding genes across organisms, using published sequences. Their data are below (base pairs given in millions, Mb).
| Organism | Genome size / Mb | Protein-coding genes | Genes per Mb |
|---|---|---|---|
| Mycoplasma (bacterium) | 0.58 | 480 | |
| E. coli | 4.6 | 4 300 | |
| Yeast | 12 | 6 000 | |
| Roundworm (C. elegans) | 100 | 20 000 | |
| Fruit fly | 140 | 14 000 | |
| Human | 3 100 | 20 000 | |
| Bread wheat | 16 000 | 100 000 | |
| Australian lungfish | 43 000 | 31 000 |
(a) Calculate genes per Mb for every organism, to 2 significant figures. [2]
(b) Describe the relationship between genome size and gene number, quoting values, and state whether it is proportional. [3]
(c) Suggest why a graph of these data should use a logarithmic scale on both axes, and describe what the plotted points would show. [2]
(d) A student concludes “wheat is five times as complex as a human because it has five times the genes.” Evaluate this conclusion using the data and your knowledge of chromosomes. [3]
(e) Identify one limitation of the data set as evidence for a general rule, and explain its effect. [2]
Model answer
(a) Genes per Mb = number of genes ÷ genome size in Mb
Mycoplasma: 480 ÷ 0.58 = 830
E. coli: 4 300 ÷ 4.6 = 930
Yeast: 6 000 ÷ 12 = 500
Roundworm: 20 000 ÷ 100 = 200
Fruit fly: 14 000 ÷ 140 = 100
Human: 20 000 ÷ 3 100 = 6.5
Wheat: 100 000 ÷ 16 000 = 6.3
Lungfish: 31 000 ÷ 43 000 = 0.72
(b) Gene number rises with genome size at first — from 480 genes in 0.58 Mb to 20 000 in 100 Mb — but then levels off: the human genome is 31 times the roundworm’s yet has the same 20 000 genes, and the lungfish genome is 14 times the human’s with only 31 000 genes.
Genes per Mb fall from about 900 in bacteria to 0.72 in the lungfish. The relationship is not proportional: proportionality would need genes ÷ Mb constant, and it falls by a factor of about 1 300 across the table.
(c) The values span nearly five orders of magnitude on the size axis (0.58 to 43 000 Mb) and more than two on the gene axis (480 to 100 000); on a linear axis all but the lungfish and wheat would sit in a blob at the origin.
A logarithmic scale spaces equal ratios equally, so every organism is readable. The points would rise steeply from Mycoplasma to the roundworm and then run almost flat from 100 Mb to 43 000 Mb, with wheat above the line.
(d) The conclusion fails on two counts. Bread wheat is a hexaploid: it contains three complete ancestral genomes, so most of its 100 000 genes are three copies of the same 30 000-odd genes — gene copies, not new functions.
And gene number does not measure complexity even between single-genome organisms: the roundworm, with about 1 000 cells, has as many genes as a human, and the lungfish has 14 times the human’s DNA for only half as many genes again.
What differs between organisms is largely how genes are regulated, which lies in non-coding DNA and cannot be read from a count.
(e) Eight organisms, chosen to include extremes (Mycoplasma, lungfish, wheat), is a small and non-random sample of the millions of species; gene counts are also estimates that change as annotation improves, so a “protein-coding gene” is not counted the same way in each organism.
Effect: the flat region from 100 Mb upwards rests on only five points, one of which (wheat) is polyploid, so the rule “gene number saturates near 20 000” is suggested but not established; adding many plants, insects and fish at intermediate sizes would test it.
Probe deeper — exam-style questions
Attempt every question before opening the answer. Marks in brackets show what a full answer is worth.
Place these in order from largest to smallest and state which one is “a section of” the next: nucleotide, chromosome, nucleus, gene, DNA molecule.
Reveal answer
Nucleus → chromosome → DNA molecule → gene → nucleotide [1]; a gene is a section of the DNA molecule, and a nucleotide is one unit of it [1].
One strand of DNA reads G G A T C C T A. Write the complementary strand and state the rule you used.
Reveal answer
C C T A G G A T [1]; complementary base pairing — A always pairs with T and C always pairs with G [1].
Define homologous chromosomes and explain, with reference to alleles, why the two chromosomes of a homologous pair are not necessarily identical.
Reveal answer
A pair of chromosomes of the same size carrying the same genes at the same loci, one inherited from each parent [1]; each gene can exist as alternative forms — alleles — differing in base sequence [1]; the chromosome from the mother may carry one allele at a locus and the one from the father a different allele, making the individual heterozygous there [1].
A student writes “the child inherited the gene for dimples from her father.” Identify the error and rewrite the sentence correctly.
Reveal answer
The error is “gene”: every person has the dimples gene at the same locus; what the father passed on is a particular allele [1]. “The child inherited the dominant allele (D) of the dimples gene from her father” [1].
A bacterium’s single chromosome is 4.6 × 10⁶ base pairs long. Calculate its stretched length in millimetres, and compare it with the 2 μm length of the cell.
Reveal answer
4.6 × 10⁶ × 0.34 × 10⁻⁹ m = 1.56 × 10⁻³ m [1] = 1.6 mm [1].
That is 1.6 × 10⁻³ ÷ 2 × 10⁻⁶ = about 800 times the length of the cell, so even a bacterial chromosome must be tightly coiled to fit [1].
Outline how a karyotype is made from a blood sample and state two things it can reveal and one it cannot.
Reveal answer
White blood cells are cultured, treated with colchicine to arrest them in division with condensed chromosomes, burst on a slide, stained and photographed; the chromosome images are arranged in pairs by size [1]. It reveals the chromosome number (an extra 21 in Down syndrome) and the sex chromosomes (XX or XY) [1]; it cannot reveal a change of one or a few bases within a gene, such as the cystic fibrosis allele [1].
7. A sperm cell contains 3.1 × 10⁹ base pairs of nuclear DNA in a head about 5 μm long. A liver cell, 20 μm across, contains 6.2 × 10⁹. Calculate the DNA length per micrometre of cell size for each, and use the result together with your knowledge of chromosome packing to explain why sperm DNA must be packed differently from the DNA of a working cell.
Reveal answer
Sperm: 3.1 × 10⁹ × 0.34 × 10⁻⁹ = 1.05 m in 5 μm, so 0.21 m per μm [1]; liver: 2.1 m in 20 μm, 0.105 m per μm [1] — the sperm packs twice the DNA per micrometre of cell into a head that also holds almost nothing else [1].
A liver cell keeps its DNA loosely spread so that genes can be read continuously, condensing it only at division; a sperm reads no genes on its journey and needs the smallest, most streamlined head possible, so its DNA is condensed to a near-crystalline state (on special packaging proteins rather than ordinary histones) and unpacked only after fertilisation [1].
8. Mules (63 chromosomes) are almost always sterile, but a mule’s body cells divide normally by mitosis throughout its life. Using what you know about homologous pairs, explain why an odd chromosome number is no problem for mitosis but prevents the formation of gametes, and predict the chromosome number of a “hinny”, the offspring of a male horse (64) and a female donkey (62).
Reveal answer
Mitosis copies each chromosome and separates the two copies; it never needs chromosomes to pair, so 63 unpaired chromosomes are copied and shared out as easily as 46 [1]. Gamete formation (meiosis, Lesson 2) begins by pairing each chromosome with its homologue; a mule has 32 horse chromosomes and 31 donkey chromosomes that do not match, so pairing fails and the gametes formed are unbalanced and non-functional [1] — hence sterility [1].
A hinny receives 32 chromosomes from the horse sperm and 31 from the donkey egg: 63, the same as a mule, and sterile for the same reason [1].
Summary
- One molecule, five magnifications: the nucleus holds chromosomes; a chromosome is supercoiled DNA; a gene is a section of DNA coding for a protein; a nucleotide (phosphate, sugar, base) is one unit of the strand.
- DNA is a double helix of two sugar-phosphate backbones joined by complementary base pairs: A–T and C–G. The base sequence is the code; the pairing is the copying mechanism.
- Human body cells have 46 chromosomes in 23 homologous pairs — one of each pair from each parent, same genes at the same loci — including XX or XY. Gametes carry 23.
- A gene has a locus; its alternative versions are alleles. Homozygous = two identical alleles, heterozygous = two different; genotype is the alleles, phenotype the trait.
- The human genome is 3.1 × 10⁹ base pairs with about 20 000 genes; genome size does not predict gene number or complexity. The Human Genome Project (1990–2003) gave one reference; the 2023 pangenome maps human variation.
Next time → Mitosis and meiosis: how a cell copies 46 chromosomes without losing one, how a gamete ends up with 23, and where the variation between brothers and sisters comes from.