Biological Basis of Life: Cell, DNA Replication, Protein Synthesis, Mutation and Meiosis

1.7 The biological basis of life: The Cell, DNA structure and Replication, Protein Synthesis, Gene, Mutation, Chromosomes and Cell Division

Official Syllabus: Paper I, Unit 1.7

Physical anthropology studies human variation and evolution, and both rest on the molecules of the cell. The sickle-cell gene of India’s tribal belt, the mitochondrial DNA that traces our African origin, the ancient DNA of Neanderthals (Unit 1.6c) and the chromosomal disorders of Unit 9.4 all make sense only once the cell, DNA, genes and cell division are understood. The forces that change gene frequencies are in Unit 1.4b (in brief: mutation supplies new variation, and selection, drift and gene flow sort it); human genetic methods are in Unit 9.

1. The Cell

1.1 Cell theory

In 1665 the English scientist Robert Hooke saw the walls of dead cork and called them “cells”; Antonie van Leeuwenhoek saw living cells in the 1670s; Robert Brown described the nucleus in 1831.

• Cell theory: the German botanist Matthias Schleiden (1838) and the German physiologist Theodor Schwann (1839) proposed that all plants and animals are made of cells; the German pathologist Rudolf Virchow (1855) added that every cell arises from a pre-existing cell (omnis cellula e cellula). The theory makes the cell the unit of structure, function and inheritance: growth, repair and reproduction are all cell division.
• Scale: a human body has roughly 30–37 trillion cells.

1.2 Prokaryotic and eukaryotic cells

Cells come in two basic designs; the key difference is the nucleus and membrane-bound organelles.

Feature	Prokaryotic cell	Eukaryotic cell
Examples	Bacteria, blue-green algae, mycoplasma	Protists, fungi, plants, animals
Nucleus	None; DNA lies free in the cytoplasm	True nucleus with a double envelope
DNA	One circular chromosome, plus plasmids	Several linear chromosomes on histones
Organelles	None bound by membranes	Mitochondria, ER, Golgi, lysosomes
Ribosomes	70S	80S (70S in mitochondria)

The 70S ribosomes and circular DNA inside mitochondria betray their past: in the endosymbiotic theory of the American biologist Lynn Margulis (1967), mitochondria descend from engulfed bacteria.

1.3 The parts of a eukaryotic cell

The table lists the main organelles; the last column shows why each matters to an anthropologist.

Part	Function	Anthropological relevance
Plasma membrane (fluid mosaic model: Seymour Singer and Garth Nicolson, 1972)	Phospholipid bilayer with proteins; controls entry and exit	Carries the ABO and HLA antigens used as genetic markers (Unit 9.6)
Nucleus, with nucleolus	Stores DNA; makes RNA; nucleolus makes ribosomes	Source of nuclear DNA
Ribosomes; endoplasmic reticulum	Ribosomes make proteins; rough ER carries ribosomes, smooth ER makes lipids and steroid hormones	Translation (§4); hormones of growth (Unit 10)
Golgi apparatus (Camillo Golgi, 1898)	Modifies, packages and dispatches proteins; adds sugars	Builds the sugar chains of the ABO antigens
Lysosomes (Christian de Duve, 1955)	Digestive enzymes	Missing enzymes cause storage diseases such as Tay-Sachs
Mitochondria	Aerobic respiration: make energy as ATP	Own mtDNA, inherited from the mother (§9)
Centrosome	Pair of centrioles; organises the spindle	Errors cause aneuploidy (§8)

2. DNA: The Genetic Material and Its Structure

2.1 How DNA was shown to be the genetic material

Each experiment answered one question, which is why they are taught in sequence.

Experiment	Year	What was done	What it proved
Frederick Griffith	1928	Heat-killed virulent pneumonia bacteria transformed harmless live ones	A “transforming principle” carries heredity
Oswald Avery, Colin MacLeod and Maclyn McCarty	1944	Destroyed each type of molecule in turn; only destroying DNA stopped transformation	The principle is DNA
Alfred Hershey and Martha Chase	1952	Labelled virus DNA and protein; only DNA entered bacteria	Viral genes are DNA, not protein
Erwin Chargaff	1950	Measured bases in many species	A = T and G = C

2.2 The double helix

In April 1953 the American James Watson and the British Francis Crick proposed the double helix in Nature, using X-ray photographs by Rosalind Franklin (notably “Photo 51”, 1952) and Maurice Wilkins, and Chargaff’s rules.

• Building block: a nucleotide = phosphate + deoxyribose sugar + base. Bases are purines (double ring: adenine, guanine) or pyrimidines (single ring: cytosine, thymine; RNA has uracil instead of thymine).
• Backbone: sugars and phosphates joined by phosphodiester bonds form the rails; bases point inwards.
• Base pairing: A pairs with T by two hydrogen bonds, G with C by three. A purine always faces a pyrimidine, so every rung has the same width (helix about 2 nm across). The strands are therefore complementary: one fixes the sequence of the other.
• Antiparallel strands: one runs 5′ to 3′ (named after the carbon atoms of the sugar), the other 3′ to 5′, which decides how DNA is copied (§3).
• Dimensions: a right-handed helix with about 10 base pairs per turn, 0.34 nm between pairs and 3.4 nm per turn, with a major and a minor groove in which proteins read the bases.
• Why the structure explains heredity: each strand is a template for copying, the base sequence stores information, and a rare mispairing explains mutation.

2.3 DNA and RNA compared

The differences explain why DNA stores information and RNA works with it.

Feature	DNA	RNA
Sugar	Deoxyribose	Ribose
Bases	A, G, C, T	A, G, C, U
Strands	Double helix	Usually single
Stability	Stable	Short-lived (most mRNA)
Role	Stores information	Carries and uses it: mRNA, tRNA, rRNA

DNA’s double strand makes it chemically stable, which is why bones yield ancient genomes. The human genome has about 3.1 billion base pairs per set of 23 chromosomes and about 20,000 protein-coding genes; only about 1.5 per cent codes for protein, and the DNA of one cell, stretched out, would be about 2 m long.

3. DNA Replication

3.1 Semi-conservative replication

Watson and Crick predicted that each daughter molecule would contain one old and one new strand: semi-conservative replication. The alternatives were conservative (the old helix stays whole beside a wholly new one) and dispersive (old and new pieces mixed).

• The proof: in 1958 Matthew Meselson and Franklin Stahl grew E. coli on heavy nitrogen (¹⁵N), moved it to normal nitrogen (¹⁴N) and separated DNA by density. After one generation all DNA was of intermediate density, ruling out the conservative model; after two, half was intermediate and half light, ruling out the dispersive model (Worked Example 2).
• In chromosomes: J. Herbert Taylor (1957) showed the same in broad-bean root cells using radioactive thymidine.

3.2 The machinery of replication

Copying happens in the S phase of the cell cycle (§8), from many origins of replication (one in E. coli; tens of thousands in a human cell).

Enzyme or protein	What it does
Helicase	Breaks hydrogen bonds and opens the replication fork
Topoisomerase	Relieves the twisting ahead of the fork
Primase	Lays a short RNA primer, since DNA polymerase cannot start a chain
DNA polymerase	Adds nucleotides only to a free 3′ end, so builds 5′ to 3′; also proofreads
DNA ligase	Seals the pieces into one strand

Leading and lagging strands. Because the strands are antiparallel and polymerase works only 5′ to 3′, one new strand (the leading strand) grows continuously towards the fork, while the other (the lagging strand) is made in short pieces, the Okazaki fragments (Reiji and Tsuneko Okazaki, 1968; 1,000–2,000 nucleotides in bacteria, 100–200 in eukaryotes), later joined by ligase.

• Accuracy: proofreading and mismatch repair cut errors to about one in a billion bases; the leftover errors are spontaneous mutations, about 60–70 new in each child (Unit 1.4b).
• Telomeres: the lagging strand cannot be finished at the tip of a linear chromosome, so ends shorten with each division. They are protected by telomeres (TTAGGG repeats), which telomerase extends in germ and stem cells (Elizabeth Blackburn, Carol Greider and Jack Szostak, Nobel Prize 2009). In most body cells telomeres shorten until division stops, part of the explanation of the Hayflick limit (about 50 divisions) and of ageing (Unit 10b).

4. Protein Synthesis and Gene Expression

4.1 From gene to protein

Proteins do the body’s work, and their link to genes was first seen in a human disease. In 1902 the English physician Archibald Garrod noticed that alkaptonuria (black urine) ran in families, often among children of cousin marriages, and behaved as a Mendelian recessive; he called such disorders “inborn errors of metabolism” (Croonian lectures, 1908): a missing enzyme caused by a faulty gene. George Beadle and Edward Tatum (1941) proved the link in the mould Neurospora: “one gene, one enzyme”, later refined to one gene, one polypeptide (one protein chain).

• The central dogma (Francis Crick, 1958): information flows DNA → RNA → protein. Howard Temin and David Baltimore (1970) found the exception, reverse transcriptase, by which RNA viruses such as HIV copy RNA into DNA.

4.2 Transcription: DNA to RNA

• How: in the nucleus, RNA polymerase binds the promoter, a control sequence upstream of the gene (often with a TATA box), unwinds the DNA and reads the template strand 3′ to 5′, building messenger RNA (mRNA) 5′ to 3′ with U opposite A. The mRNA thus matches the other, coding strand, with U for T.
• Processing: the pre-mRNA gets a protective 5′ cap and poly-A tail, and splicing removes non-coding introns and joins exons (split genes, discovered by Phillip Sharp and Richard Roberts, 1977); alternative splicing lets one gene make several proteins.
• Other RNAs: tRNA carries amino acids; rRNA forms the ribosome; microRNAs regulate genes.

4.3 The genetic code

The message is read in codons of three bases: two bases give only 16 combinations, too few for 20 amino acids, while three give 64 (Worked Example 3).

• Deciphering: Marshall Nirenberg and Heinrich Matthaei (1961) found that synthetic RNA of pure U makes a chain of phenylalanine (UUU = Phe); the Indian-born American chemist Har Gobind Khorana decoded the rest with repeating sequences, and Robert Holley solved tRNA structure (Nobel Prize, 1968).
• Properties:
  • Triplet, read from a fixed start; AUG (methionine) starts, UAA, UAG and UGA stop.
  • Degenerate: most amino acids have several codons, usually differing in the third base (Crick’s wobble hypothesis, 1966), so many base changes are silent.
  • Unambiguous: each codon means one amino acid.
  • Non-overlapping and comma-less, so an inserted or deleted base shifts the whole reading frame (§6).
  • Nearly universal, strong evidence of the common origin of life; mitochondria are an exception (UGA = tryptophan).

4.4 Translation: RNA to protein

1. Activation: each amino acid is joined to its own tRNA by an aminoacyl-tRNA synthetase, using ATP; the tRNA’s anticodon pairs with the codon.
2. Initiation: the small ribosomal subunit binds the mRNA at the AUG start codon; the tRNA carrying methionine pairs with it; the large subunit joins.
3. Elongation: the ribosome has three sites: A (arriving tRNA), P (holding the growing chain) and E (exit). A peptide bond joins the chain to each new amino acid (catalysed by the ribosome’s own rRNA), and the ribosome moves one codon along.
4. Termination: at a stop codon a release factor frees the chain, which then folds. Several ribosomes (a polysome) can read one mRNA at once.

4.5 Gene expression and its regulation

A nerve cell and a liver cell carry the same genome but make different proteins. Gene expression is the use of a gene’s information to make its product; regulation decides which genes are expressed, when and how much.

• The operon model: François Jacob and Jacques Monod (1961) showed why bacteria make lactose-digesting enzymes only when lactose is present. In the lac operon, three structural genes share a promoter and an operator; a regulator gene makes a repressor that sits on the operator; lactose (the inducer) pulls the repressor off and the genes switch on. Genes are thus controlled by other genes and the environment.
• In eukaryotes: transcription factors binding enhancers and silencers, and epigenetic marks (DNA methylation, histone modification) that open or close chromatin without changing the sequence.
• Human examples:
  • X-inactivation: one X is silenced in each female cell (Mary Lyon, 1961), visible as the Barr body, so women are mosaics for X-linked genes.
  • Lactase persistence: a regulatory mutation keeps the lactase gene on in adults in many pastoral populations, including in north-west India, a case of gene–culture co-evolution (Unit 1.4a).

5. The Gene

5.1 How the concept developed

The table shows each stage in the idea of the gene and what it added.

Scholar (year)	Concept
Gregor Mendel (1866)	Discrete “factors” (Elemente), one from each parent
Walter Sutton and Theodor Boveri (1902–03)	Factors lie on chromosomes, whose behaviour in meiosis explains Mendel’s laws
Wilhelm Johannsen (1909)	Coined “gene“, “genotype” and “phenotype”
Thomas Hunt Morgan (1910s)	Genes in linear order on chromosomes, like beads; linkage maps
Beadle and Tatum (1941)	One gene, one enzyme
Seymour Benzer (1955–57)	Cistron (unit of function), recon (unit of recombination), muton (unit of mutation)
Sharp and Roberts (1977)	Split genes: exons and introns

The sequence runs from an abstract unit to a physical, regulated segment of DNA: a gene is now defined as a DNA sequence, with its control regions, transcribed into a functional product (protein or RNA).

• Structure: promoter, exons, introns and untranslated ends; a locus is its position, alleles its alternative forms.
• Kinds: structural and regulator genes; housekeeping and tissue-specific genes; pseudogenes (inactive copies, useful as molecular fossils).

5.2 Lethal and sub-lethal genes

• Lethal genes kill before reproductive age. The French geneticist Lucien Cuénot (1905) found that yellow × yellow mice gave 2 yellow : 1 non-yellow, because homozygous yellow embryos die (Worked Example 7).
  • Recessive lethals hide in carriers, as in Tay-Sachs disease (death in early childhood); homozygous achondroplasia is lethal while the heterozygote lives.
  • Dominant lethals persist only if they act late, as in Huntington’s disease, which often begins after children are born.
• Sub-lethal (semi-lethal) genes kill some carriers of the trait before adulthood or shorten life: haemophilia, thalassaemia major, untreated sickle-cell anaemia. Medical care turns them into chronic conditions, which raises the genetic load (Unit 9.3).

5.3 Mendelian and non-Mendelian traits

A Mendelian trait depends on one gene with clear alleles and follows simple ratios; most human traits do not.

	Mendelian (single-gene)	Non-Mendelian
Basis	One locus; dominant or recessive alleles	Many genes and environment, or unusual transmission
Variation	Discontinuous	Often continuous
Examples	ABO and Rh groups, albinism, PTC tasting, sickle-cell anaemia	Stature, skin colour (polygenic); diabetes (multifactorial); mitochondrial traits; genomic imprinting

Mendelian traits make good genetic markers because each genotype can be read directly; popular “race” categories rested instead on polygenic traits such as skin colour (Unit 9.5).

5.4 The thrifty genotype

• The hypothesis: the American geneticist James Neel (1962) asked why diabetes, which harms fitness, is so common. He proposed “thrifty” genes that stored fat efficiently and were favoured in cycles of feast and famine, but became harmful under modern plenty, “rendered detrimental by progress”; the Pima of Arizona were a key example.
• Criticism: famines were rarely severe enough to select so strongly, and no clear thrifty genes have been found; John Speakman (2008) proposed that obesity genes spread by drift instead.
• The thrifty phenotype: Nicholas Hales and David Barker (1992) traced the risk instead to poor nutrition in the womb, which programmes a body for scarcity. Chittaranjan Yajnik and colleagues in Pune described the “thin-fat Indian baby“, small at birth but relatively fat and prone to later diabetes, which fits this developmental view.

6. Mutation

6.1 A mutation in India’s tribal belt

Among many tribal communities of central and western India, people carry a single changed letter in the beta-globin gene on chromosome 11: codon 6 has changed from GAG (glutamic acid) to GTG (valine). With two copies, red cells deform into sickles, block vessels and break down: sickle-cell anaemia. With one copy (the trait), people are mostly healthy and better protected against falciparum malaria, which is why the gene became common where malaria was rife (Anthony Allison, 1954): a balanced polymorphism (Unit 9.3). By July 2026 India’s national mission had carried out over 7.24 crore screenings in tribal areas, finding 2,47,961 patients and 20,35,181 carriers. The case shows the whole chain: a point mutation, a changed protein, a disease and selection.

6.2 Definition and kinds

A mutation is a sudden, heritable change in the genetic material, from one base to a whole chromosome; changes caused by the environment alone and not inherited are modifications. The Dutch botanist Hugo de Vries coined the term (1901); Hermann Muller (1927) showed that X-rays cause mutations; and Salvador Luria and Max Delbrück (1943) proved that mutations arise at random, not in response to need.

Basis	Types	Explanation and example
Cell affected	Somatic / germline	Somatic: only the individual (many cancers); germline: inherited
Size	Point (gene) / chromosomal	One or a few bases / number or structure of chromosomes (Unit 9.4)
Base substitution	Transition / transversion	Purine for purine or pyrimidine for pyrimidine / purine for pyrimidine
Effect on protein	Silent, missense, nonsense, frameshift	Same amino acid; a new one (sickle cell); an early stop; frame shifted by insertion or deletion
Repeat expansion	Dynamic	Three-base repeat grows: CAG in Huntington’s disease
Origin	Spontaneous / induced	Copying errors / mutagens

• Mutagens: physical (X-rays break DNA; heat raises the rate; ultraviolet light fuses neighbouring thymines); chemical (base analogues, alkylating agents such as mustard gas, tobacco smoke); biological (some viruses, transposons).
• Repair: proofreading, mismatch repair and excision repair fix most damage; in xeroderma pigmentosum, a recessive failure of excision repair, sunlight causes skin cancers.

6.3 Single-gene mutation disorders in man

The table lists the best-known single-gene disorders; the last column shows why several are public-health issues in India.

Disorder	Gene (chromosome)	Inheritance	Mutation and note
Sickle-cell anaemia	HBB (11)	Autosomal recessive	Glu → Val; tribal belt of India; national mission
Beta-thalassaemia	HBB (11)	Autosomal recessive	Reduced beta-globin; carrier screening in several Indian communities
Cystic fibrosis	CFTR (7)	Autosomal recessive	Commonest: loss of one amino acid (three bases); frequent in Europeans
Tay-Sachs disease	HEXA (15)	Autosomal recessive	Lysosomal enzyme lost; historically common in Ashkenazi Jews
Phenylketonuria	PAH (12)	Autosomal recessive	Enzyme missing; newborn screening and diet prevent brain damage
Huntington’s disease	HTT (4)	Autosomal dominant	CAG repeat expansion; late onset
Achondroplasia	FGFR3 (4)	Autosomal dominant	Mostly new mutations, often from older fathers
Haemophilia A; G6PD deficiency	F8, G6PD (X)	X-linked recessive	Affect mainly males; G6PD deficiency frequent in some Indian groups

6.4 Implications of mutation in evolution

• The ultimate source of new alleles: recombination reshuffles variation; only mutation creates new versions of genes.
• Neutral and adaptive change: most changes are neutral (Motoo Kimura, Unit 1.4b) and accumulate steadily, the basis of the molecular clock; a few are adaptive, such as lactase persistence and the Denisovan-derived EPAS1 variant for altitude (Unit 1.6c).
• Balanced polymorphism: a gene harmful in double dose is kept when carriers gain (sickle cell and malaria).
• Genetic load: hidden recessive mutations surface more often in consanguineous marriages (Unit 9.3).
• A tracer of history: shared mutations in mitochondrial DNA and the Y chromosome define haplogroups that map human migrations (§9).

7. Chromosomes

7.1 Discovery, number and structure

• History: the German anatomist Wilhelm Waldeyer coined “chromosome” (“coloured body”) in 1888; in 1956 Joe Hin Tjio and Albert Levan counted the human number as 46, not the 48 long assumed.
• Human karyotype: 22 pairs of autosomes and one pair of sex chromosomes: 46,XX in females, 46,XY in males. Gametes are haploid (23, n); body cells diploid (46, 2n).
• Other species: chimpanzee and gorilla have 48. Human chromosome 2 formed by the fusion of two ape chromosomes: its bands match two chimpanzee chromosomes and it keeps a second, inactive centromere and telomere remnants in its middle, direct evidence of common descent.
• Packing: DNA wraps about 147 base pairs around eight histones to form a nucleosome (Roger Kornberg, 1974); further coiling compacts it about 10,000-fold at metaphase.
• Parts: two sister chromatids joined at the centromere (primary constriction), where kinetochores attach the spindle; a short arm (p) and a long arm (q); telomeres at the ends; satellites on acrocentric chromosomes carrying the ribosomal RNA genes that form the nucleolus.
• Euchromatin and heterochromatin: loosely packed, active euchromatin against densely packed, mostly inactive heterochromatin, either permanent (around centromeres, most of the Y) or facultative (the inactive X of the Barr body).

7.2 Types by centromere position

The table lists the four shapes with human examples; humans have no telocentric chromosomes.

Type	Centromere	Human examples
Metacentric	Middle; equal arms	1, 3, 16, 19, 20
Submetacentric	Off-centre	2, 4–12, 17, 18, X
Acrocentric	Near one end; tiny p arm with satellites	13, 14, 15, 21, 22, Y
Telocentric	At the end	None in humans

Two acrocentric chromosomes can fuse at their centromeres (a Robertsonian translocation), which causes some inherited cases of Down syndrome.

7.3 Karyotype

• Method: white blood cells are grown, stopped at metaphase with colchicine (which blocks the spindle), swollen, spread, stained and photographed; chromosomes are arranged in pairs by size and centromere (the Denver groups A–G, 1960).
• Banding: G-banding (Giemsa stain) and Q-banding (quinacrine; Torbjörn Caspersson, 1970) give each chromosome a barcode of bands, so missing, extra or moved segments can be seen.
• Uses: diagnosis of numerical and structural aberrations, prenatal testing and species comparison (Unit 9.4).

8. Cell Division

8.1 The cell cycle

• Phases: interphase, with G1 (growth), S (DNA replication, giving two chromatids per chromosome) and G2 (preparation), then the M phase (division). Cells that stop dividing, such as most nerve cells, rest in G0. Interphase is sometimes called a “resting stage”, but the cell is busy.
• Timing: a cultured human cell divides about every 24 hours, mitosis taking about one hour.
• Control: checkpoints run by cyclins and their kinases (Leland Hartwell, Tim Hunt and Paul Nurse, Nobel 2001) stop the cycle if DNA is damaged; p53, “guardian of the genome”, halts damaged cells. Cancer is division out of control: overactive oncogenes (stuck accelerators) and lost tumour-suppressor genes (failed brakes).

8.2 Mitosis

Mitosis (named by Walther Flemming, 1882) is the equational division of body cells: one cell gives two cells with the same 46 chromosomes.

1. Prophase: chromatin condenses into chromosomes of two chromatids; the nucleolus fades; the spindle forms.
2. Prometaphase: the nuclear envelope breaks down; spindle fibres attach to kinetochores.
3. Metaphase: chromosomes line up on the equator, the best stage for counting them.
4. Anaphase: centromeres split; sister chromatids move to opposite poles.
5. Telophase and cytokinesis: nuclei re-form, ending karyokinesis (nuclear division); the cytoplasm divides by a cleavage furrow (animals) or a cell plate (plants).

Significance: mitosis keeps the chromosome number and genetic content identical, driving growth and repair.

8.3 Meiosis

Meiosis (named by J.B. Farmer and J.E.S. Moore, 1905) is the reduction division that makes gametes: one diploid cell gives four haploid cells through two divisions after one round of DNA replication.

Meiosis I (reductional: homologues separate)

• Prophase I has five stages:
  1. Leptotene: chromosomes condense into long threads.
  2. Zygotene: homologous chromosomes pair (synapsis), held by the synaptonemal complex, forming bivalents.
  3. Pachytene: each bivalent shows four chromatids (a tetrad); crossing over, the exchange of segments between non-sister chromatids, takes place.
  4. Diplotene: the synaptonemal complex dissolves; homologues stay joined at chiasmata, the X-shaped points of exchange. Human oocytes wait here (dictyotene) from before birth until ovulation, sometimes for 40 years or more.
  5. Diakinesis: chromosomes condense fully; chiasmata move to the ends (terminalisation).
• Metaphase I: bivalents line up on the equator, each pair oriented at random.
• Anaphase I: homologues go to opposite poles; sister chromatids stay together.
• Telophase I: two haploid cells; a brief interkinesis follows without DNA replication.

Meiosis II (equational, like mitosis): in each cell centromeres split and sister chromatids separate, giving four haploid cells.

The comparison answers the commonest question on cell division; the decisive rows are pairing, crossing over and what separates at anaphase.

Feature	Mitosis	Meiosis
Where	Body cells	Germ cells in testis and ovary
Divisions	One	Two
Products	Two diploid, identical cells	Four haploid, genetically different cells
Pairing and crossing over	No	Yes (zygotene, pachytene)
Anaphase separates	Sister chromatids	Homologues (I), then chromatids (II)
Purpose	Growth and repair	Gametes; constant number; variation

8.4 The genetic significance of meiosis

• The physical basis of Mendel’s laws (Sutton, 1902–03): segregation is the separation of homologues at anaphase I; independent assortment is the random orientation of bivalents at metaphase I.
• Variation: random orientation alone gives 2²³, about 8.4 million, kinds of gamete per person, and two parents about 70 trillion possible children, before crossing over multiplies the number further (Worked Example 6). This is the raw material of natural selection, and the reason why no two people except identical twins are genetically alike, the basis of DNA fingerprinting.
• Errors: non-disjunction gives gametes with an extra or a missing chromosome: Down syndrome (trisomy 21), Turner (45,X) and Klinefelter (47,XXY) syndromes (Unit 9.4). Most trisomy 21 arises in maternal meiosis I, and its risk rises with maternal age, probably because oocytes wait decades in prophase I.
• Gametogenesis: in spermatogenesis a primary spermatocyte gives four sperm; in oogenesis a primary oocyte gives one ovum and polar bodies; halving here and restoring at fertilisation keeps the number at 46.

9. Nuclear and Mitochondrial DNA

The two genomes differ in almost every respect, and each difference has a use.

Feature	Nuclear DNA	Mitochondrial DNA (mtDNA)
Size	About 3.1 billion base pairs per set	16,569 base pairs
Shape	Linear, in 46 chromosomes with histones	Circular, without histones
Genes	About 20,000 protein-coding	37 (13 proteins, 22 tRNAs, 2 rRNAs)
Copies per cell	Two of each chromosome	Hundreds to thousands
Inheritance	Both parents	Mother only
Recombination	Yes	None
Mutation rate	Lower	About 10 times higher, mainly in the control region

• Why mtDNA suits evolutionary studies: it passes unchanged down the female line, so differences between people arise only from mutations that build up with time, giving one datable family tree.
• Human evolution: the “mitochondrial Eve” study (Rebecca Cann, Mark Stoneking and Allan Wilson, 1987) found the deepest lineages in Africa and traced all living mtDNA to one woman about 200,000 years ago; haplogroups M and N mark the out-of-Africa dispersal, and the Andamanese carry unique, deep M lineages (Kumarasamy Thangaraj and colleagues, 2005); Neanderthal (1997) and Denisovan (2010) mtDNA first showed these were separate lineages (Unit 1.6c).
• Uses and limits: many copies survive in old remains, which helps forensics and ancient DNA; but mtDNA records only the maternal line, so the Y chromosome and whole genomes are needed for the full picture.
• Medicine: mtDNA mutations cause diseases such as Leigh syndrome, passed from a mother to all her children. In mitochondrial donation the nucleus of an affected mother’s egg or embryo is moved into a donor egg with healthy mitochondria; the UK reported eight healthy babies born this way (Newcastle, July 2025).

10. Worked Examples

1. Chargaff’s rules. A DNA sample has 30 per cent adenine. Since A = T, T = 30 per cent; G + C = 100 − 60 = 40, and G = C, so G = C = 20 per cent. Check: purines (A + G = 50) equal pyrimidines (T + C = 50). More G + C means more triple bonds and more heat-stable DNA.

2. Meselson and Stahl. Heavy (¹⁵N) bacteria are moved to light (¹⁴N) medium.

• Generation 1: 2 molecules, both hybrid (100 per cent).
• Generation 2: 4 molecules, 2 hybrid and 2 light (50 per cent).
• Generation 3: 8 molecules, 2 hybrid and 6 light (25 per cent).
• Rule: the two original strands are never lost, so the hybrid fraction after n generations is 2 / 2ⁿ. A conservative model would instead give separate heavy and light bands after generation 1.

3. Why a triplet code? With 4 bases, words of length k number 4^k: 4 for k = 1, 16 for k = 2 (fewer than 20 amino acids) and 64 for k = 3, of which 61 code for amino acids and 3 are stops, so the code is degenerate.

4. From gene to protein. Template DNA (3′ to 5′): TAC CTC TTT ATT → mRNA (5′ to 3′): AUG GAG AAA UAA → Met–Glu–Lys, then stop. The coding strand reads ATG GAG AAA TAA, the mRNA with T for U.

5. One sequence, four mutations. Start with mRNA AUG GAG AAA UGG UAA (Met–Glu–Lys–Trp–stop).

Change	New mRNA	Protein	Type
GAG → GAA	AUG GAA AAA UGG UAA	Met–Glu–Lys–Trp	Silent
GAG → GUG	AUG GUG AAA UGG UAA	Met–Val–Lys–Trp	Missense (the sickle-cell change)
UGG → UGA	AUG GAG AAA UGA	Met–Glu–Lys, then stop	Nonsense
First G of GAG deleted	AUG AGA AAU GGU AA…	Met–Arg–Asn–Gly…	Frameshift

The table shows why frameshifts are usually the most damaging and silent changes harmless: the reading frame matters more than any single letter.

6. Chromosomes and DNA through the cycle (n = 23; C = DNA of one haploid set).

Stage	Chromosomes	Chromatids each	DNA
G1 body cell	46	1	2*C*
G2 (after S phase)	46	2	4*C*
Each daughter of mitosis	46	1	2*C*
Each cell after meiosis I	23	2	2*C*
Each gamete after meiosis II	23	1	1*C*

Independent assortment gives 2²³ = 8,388,608 kinds of gamete per parent, and 2²³ × 2²³, about 7 × 10¹³ (70 trillion), possible children of one couple, before crossing over.

7. A lethal gene. Yellow × yellow mice (Yy × Yy; Cuénot, 1905) should give 1 YY : 2 Yy : 1 yy. YY embryos die, so the living offspring are 2 yellow : 1 non-yellow, in litters about a quarter smaller. The gene is dominant for colour but recessive for lethality; a departure from 3 : 1 reveals it.

Key Terms

Term	Meaning in simple words
Eukaryote	An organism whose cells have a true nucleus
Nucleotide	The unit of DNA or RNA: phosphate, sugar and base
Complementary	Matching by base pairing: A with T (or U), G with C
Semi-conservative replication	Copying in which each new DNA keeps one old strand
Okazaki fragments	Short pieces in which the lagging strand is made
Transcription / translation	Copying DNA into RNA / reading RNA to build a protein
Codon / anticodon	Three mRNA bases for one amino acid / the matching bases on tRNA
Intron / exon	Part of a gene cut out of the RNA / part kept
Operon	A group of bacterial genes switched on and off together
Epigenetic	A change in gene activity without a change in DNA sequence
Lethal gene	A gene that kills before reproductive age
Missense / nonsense / frameshift	A new amino acid / an early stop / a shifted reading frame
Karyotype	A cell’s chromosomes photographed and arranged in pairs
Chiasma	The X-shaped point where homologues exchanged segments
Non-disjunction	Failure of chromosomes to separate in division

Contemporary Developments

• A complete personal genome (August 2026): scientists assembled both parental copies of every chromosome of a reference human genome from telomere to telomere, adding over 900 million DNA letters missing from earlier benchmarks, at about 5,000 dollars (Adam Phillippy and colleagues).
• Base editing in human embryos (June–July 2026): two studies used base editing, which changes a single DNA letter, to edit donated IVF embryos precisely, reopening the debate on germline editing.
• One-shot gene editing for cholesterol (September 2026): a single infusion of a CRISPR therapy switching off the ANGPTL3 gene halved “bad” cholesterol for a year in a first trial of 15 patients (Cleveland Clinic; New England Journal of Medicine).
• India’s sickle-cell drive (July 2026): the National Sickle Cell Anaemia Elimination Mission (launched July 2023) had made over 7.24 crore screenings (Ministry of Tribal Affairs); BIRSA 101, India’s first indigenous CRISPR therapy for sickle-cell disease (CSIR-IGIB), was launched in November 2025, with first trials expected in 2027.

Diagrams to Master

1. Topic map: cell → DNA → replication → protein synthesis → gene → mutation → chromosomes → division.
2. Double helix: backbone, A=T (2 bonds), G≡C (3 bonds), 5′ and 3′ ends, 2 nm, 3.4 nm per turn.
3. Replication fork: helicase, primase, leading strand, Okazaki fragments, ligase.
4. Protein synthesis: transcription → splicing → mRNA → ribosome (A, P, E) → protein.
5. Mutation types: one sequence with silent, missense, nonsense, frameshift.
6. Mitosis and meiosis: 2*n* → two 2*n*; 2*n* → bivalents with chiasmata → four n.

Revision Grid

Scholar	Work (year)	Key idea
Schleiden, Schwann; Virchow	1838–39; 1855	Cell theory
Garrod	1902–08	Inborn errors of metabolism
Avery, MacLeod and McCarty	1944	DNA is the genetic material
Watson and Crick	Nature (1953)	Double helix
Meselson and Stahl	1958	Semi-conservative replication
Crick	1958	Central dogma
Jacob and Monod	1961	Lac operon
Nirenberg, Khorana and Holley	1961–66	Genetic code
Neel	1962	Thrifty genotype
Tjio and Levan	1956	46 human chromosomes
Sharp and Roberts	1977	Split genes
Cann, Stoneking and Wilson	1987	Mitochondrial Eve