1The idea in one paragraph

Every cell comes from a cell that divided. Before a eukaryotic cell divides, it copies its DNA, so each chromosome becomes two identical chromatids. Then it divides its nucleus. Mitosis separates the two chromatids of every chromosome, one to each end of the cell, so the two new nuclei are genetically identical to the old one; that is how a body grows and repairs itself. Meiosis divides the nucleus twice: first it separates the matching pairs of chromosomes, then the chromatids, so four nuclei are made, each with half the chromosome number and each with a different mix of the parent's alleles; that is how cells that will become gametes are made. Finally cytokinesis splits the cytoplasm. At HL you learn how a cell decides when to divide, and what happens when that decision goes wrong: cancer.

2Where new cells come from

In every living organism, new cells are made by cell division: a parent cell (often called the mother cell) divides to form two daughter cells. There is no other source.

In a eukaryote, division is two events, in a fixed order.

1. Nuclear division. The nucleus divides, by mitosis or by meiosis, so that each daughter will have a nucleus.
2. Cell division, or cytokinesis. The cytoplasm, with its organelles, is split between the daughters.

The order matters. If the cytoplasm were split before the nucleus had divided, one daughter would get the nucleus and the other would get none. An anucleate cell has no genes to direct protein synthesis and cannot divide again.

3Cytokinesis: splitting the cytoplasm

Cytokinesis is the division of the cytoplasm of a parent cell between the daughter cells. It usually begins as nuclear division ends. Animal and plant cells do it in opposite directions, and Figure 1 shows why.

In an animal cell, a ring of contractile proteins, actin and myosin, forms just inside the plasma membrane around the equator of the cell. The ring tightens, like a drawstring, pulling the membrane inwards to form a cleavage furrow. The furrow deepens until the membrane meets in the middle and fuses, pinching the cell in two.

In a plant cell, a drawstring cannot work: the rigid cell wall cannot be pulled inwards. Instead, vesicles from the Golgi apparatus, carrying wall materials, gather at the equator. They fuse with each other to form a flat cell plate that grows outwards until it meets the existing wall. The membranes of the vesicles become the new plasma membranes of the two daughters, and their contents become the new cell wall between them.

Animal cells divide from the outside in, by a contracting ring. Plant cells divide from the inside out, by fusing vesicles.

4Equal and unequal cytokinesis

Usually cytokinesis is equal: the two daughters get about the same volume of cytoplasm. But not always.

Whatever the split, each daughter must receive at least one mitochondrion, and a plant cell at least one chloroplast. These organelles cannot be built from scratch. New ones are made only by the growth and division of existing ones, so a daughter cell that got none could never have any. Organelles that the cell can assemble itself, such as ribosomes, need not be shared out so carefully.

Figure 2 shows two cases of unequal cytokinesis.

Oogenesis in humans. When an egg cell is being made, both divisions of meiosis are followed by very unequal cytokinesis. One daughter keeps nearly all the cytoplasm, with its food reserves and organelles, and becomes the egg. The other, a polar body, receives a nucleus and little else, and it degenerates. The point is to put as much cytoplasm as possible into one cell, because the egg must support the embryo in its first days.

Budding in yeast. Yeast (a unicellular fungus) reproduces asexually by growing a small outgrowth, a bud. The nucleus divides by mitosis and one nucleus moves into the bud, which then pinches off as a small daughter cell. The parent keeps most of the cytoplasm and can bud again.

5Two kinds of nuclear division, two jobs

Mitosis maintains the chromosome number and the genome. Meiosis halves the chromosome number and generates genetic diversity. Every other difference follows from those two sentences.

6Before either division: replicate, condense, move

DNA replication comes first. In both mitosis and meiosis, the DNA of every chromosome has already been copied during interphase. After replication, each chromosome consists of two DNA molecules, called sister chromatids. They are identical, because replication is semi-conservative and base pairing is accurate. They are held together, most tightly at a region called the centromere, until anaphase, when they are finally separated. Figure 3 follows one chromosome through this.

Condensation. An uncoiled chromosome is a DNA molecule several centimetres long in a nucleus a few micrometres across. Moved in that state, it would tangle and break. So before division, chromosomes condense: the DNA, already wrapped round histone proteins in nucleosomes, is coiled and coiled again, a process called supercoiling. The chromosome becomes thousands of times shorter and much thicker, and only then is it visible with a light microscope. Condensation is shared by mitosis and meiosis.

Movement. Chromosomes are moved by the spindle, a structure of microtubules: long protein fibres that grow out from each end, or pole, of the cell. Microtubules attach to each chromosome at its centromere. Microtubule motors, proteins that use energy from ATP to move along microtubules, together with the shortening of the microtubules themselves, pull the chromosomes or chromatids towards the poles. The same machinery works in both divisions.

7The phases of mitosis

Mitosis is one continuous process, divided into four phases so it can be described. Figure 4 shows a cell with four chromosomes (2n = 4): a long pair and a short pair, one of each pair from each parent.

Prophase. The chromosomes condense and become visible as two sister chromatids joined at a centromere. Spindle microtubules begin to grow. At the end of prophase the nuclear membrane breaks down, so the spindle can reach the chromosomes.

Metaphase. Microtubules from both poles attach to the centromere of every chromosome, one sister chromatid facing each pole. The chromosomes are pulled into a single line across the equator of the cell.

Anaphase. The centromeres divide and the sister chromatids separate. Each chromatid is now a chromosome in its own right. The spindle microtubules pull them to opposite poles, centromere first, so the arms trail behind in a V shape.

Telophase. A complete set of chromosomes arrives at each pole. A nuclear membrane forms around each set, and the chromosomes uncoil. Cytokinesis usually follows.

Why are the two nuclei identical? Because every chromosome was replicated to give two identical chromatids, and in anaphase the two chromatids of every chromosome went to opposite poles. Each pole therefore receives exactly one copy of every chromosome: the same number, and the same genes, as the parent cell.

A trap: interphase is not a phase of mitosis. It is the period between divisions, when the cell grows and copies its DNA. Mitosis is prophase to telophase only.

8Identifying the phases in a micrograph

The guide expects you to name the phase of a cell in a drawing and in a real micrograph. The standard material is a root tip, squashed and stained so that the chromosomes show dark. Near the tip, cells are dividing all the time. Figure 5 is a drawing of such a field of view.

Use this sequence of questions on each cell.

So in Figure 5: A is prophase, B is metaphase, C is anaphase, D is telophase and E is interphase. Notice how few cells are dividing. Most cells in any tissue are in interphase at any moment, because interphase is by far the longest part of a cell's life. At HL you turn exactly this observation into a number (section 16).

9Meiosis: a reduction division

A diploid nucleus (2n) has two sets of chromosomes, one from each parent, so its chromosomes come in homologous pairs: two chromosomes with the same genes in the same positions, though not necessarily the same alleles. A haploid nucleus (n) has one set: one chromosome of each type. A human body cell is diploid, 2n = 46; a human gamete is haploid, n = 23.

Meiosis is a reduction division: one diploid nucleus divides twice to make four haploid nuclei. Figure 6 follows a cell with 2n = 4.

There are two rounds of segregation (separation), and they separate different things.

Meiosis I: homologous chromosomes are separated. In prophase I, the homologous chromosomes pair up, side by side, to form a bivalent (two chromosomes, four chromatids). In metaphase I the bivalents line up on the equator. In anaphase I, one chromosome of each pair goes to each pole, and the centromeres do not divide: each chromosome still has its two chromatids. Each new nucleus has one of each type of chromosome, so it is already haploid. This is the reduction.

Meiosis II: sister chromatids are separated. Each of the two haploid cells now divides much as in mitosis. Chromosomes line up, centromeres divide, and sister chromatids go to opposite poles. The result is four haploid nuclei, each with one chromatid of each chromosome type.

Why a sexual life cycle needs meiosis. Sexual reproduction joins two gametes at fertilisation. If gametes were diploid, the zygote would have four sets of chromosomes, the next generation eight, and so on, doubling each time. Meiosis halves the number once per generation and fertilisation doubles it once, so the chromosome number of the species stays constant. D3.1 builds the whole life cycle on this.

10Non-disjunction and Down syndrome

Meiosis can go wrong. In non-disjunction, a pair of homologous chromosomes fails to separate in anaphase I, or a pair of sister chromatids fails to separate in anaphase II. Both go to the same pole. Figure 7 follows chromosome 21.

One resulting gamete has two copies of chromosome 21 (n + 1, 24 chromosomes) and another has none (n − 1, 22). If the gamete with an extra copy is fertilised by a normal gamete, the zygote has three copies of chromosome 21 and 47 chromosomes in total. Every cell of the body that develops from it carries this trisomy 21, and the result is Down syndrome, with characteristic physical features and some degree of learning disability.

Non-disjunction can happen in either parent, but it happens most often during egg formation, and its likelihood rises with the age of the mother.

11Meiosis as a source of variation

Meiosis does not just halve the chromosomes. It shuffles them, in two ways. Figure 8 shows both.

Random orientation of bivalents. In metaphase I, each bivalent lines up on the equator with either homologue facing either pole. Which way one bivalent faces has no effect on the others. In Figure 8(a), with two bivalents, there are two arrangements and four possible combinations of chromosomes in the gametes. In general, with n pairs of chromosomes, the number of combinations is 2ⁿ.

Crossing over. In prophase I, while homologous chromosomes are paired, a chromatid of one can break and exchange a matching section with a non-sister chromatid of the other, at a point called a chiasma. The chromatids that result carry new combinations of alleles on one chromosome, as in Figure 8(b): alleles A and b now travel together, which neither parent's chromosome had. These recombinant chromatids are why even the same chromosome is rarely passed on unchanged.

Together, and with the random choice of which two gametes meet at fertilisation, these make every offspring of sexual reproduction genetically unique, which is the variation natural selection acts on.