Cell Cycle and Cell Division: Class 11 Biology · Chapter 10

You began as a single cell: a fertilised egg about a tenth of a millimetre across. Today your body holds something like 37 trillion cells, and every one of them descends from that first cell by division. If each division simply doubled the count, about 45 rounds would do it, since $2^{45}\approx 3.5\times {10}^{13}$. Real development is messier, with cells dividing at different rates and many dying on schedule, but the principle stands: an organism is built by cells that grow, copy themselves and split, again and again.

The cell theory you met in Chapter 8 says that new cells arise only from existing cells. This chapter asks how a cell manages that without losing or scrambling its genetic instructions. Two kinds of division answer the question: mitosis, which gives daughter cells genetically matching the parent, and meiosis, which halves the chromosome number to make cells for sexual reproduction.

10.1 Cell Cycle

Before one cell can become two working cells it has three jobs to finish: grow (make more cytoplasm, membranes and organelles), copy its DNA exactly once, and share everything out fairly. Suppose the cell split before replication was complete: a daughter would inherit a broken genome. Suppose it replicated twice: a daughter would get spare copies. So the three jobs run to a timetable, and the timetable itself is set by the cell's own genes.

Notice the asymmetry in the cell cycle. Ask when a cell is adding cytoplasm and the answer is nearly always; ask when it is copying DNA and the answer is only in one window, called S. Division then has to deliver one copy of every chromosome to each daughter nucleus (Fig. 10.1).

10.1.1 Phases of Cell Cycle

Cycle lengths vary enormously. A yeast cell can get round in about 90 minutes; human cells growing in a culture dish take about a day; and different kinds of cells in one body keep very different schedules.

Watch a cultured human cell in a time-lapse film and it seems to do little for most of a day, then splits in about an hour. That hour is M phase (mitosis phase). The long stretch from the end of one M phase to the start of the next is interphase. With about 23 of the 24 hours spent there, interphase takes up more than 95 % of the cycle.

M phase has two parts of its own. First the nucleus divides, and the separated daughter chromosomes are gathered into two new nuclei: this is karyokinesis (Greek karyon, kernel or nucleus, and kinesis, movement). Usually the cytoplasm is then cut in two, which is cytokinesis (cyto-, cell).

That apparent idleness earned interphase the old nickname resting phase. The name misleads: interphase is the preparation, when the cell grows and replicates its DNA in a set order. It has three sub-phases:

• G1 (gap 1): grow first. A newly formed daughter cell is small. Working at full metabolic speed, it builds proteins, organelles and cytoplasm, while its DNA stays exactly as it is: no replication yet.
• S (synthesis): copy the genome. Every DNA molecule is replicated once, taking the cell from 2C to 4C. Centromeres are not doubled, so the cell still has 2n chromosomes, each now a pair of sister chromatids. In an animal cell the centriole is copied in the cytoplasm at the same time.
• G2 (gap 2): stock up for mitosis. Growth goes on, and the cell makes the proteins that division will need.

Two different counts are in play here, so keep them apart. C stands for the amount of DNA in one haploid set of chromosomes, so a diploid nucleus in G1 holds 2C. n counts chromosomes, and a chromosome is counted by its centromere. Replication doubles C, but it adds no centromeres, so it leaves the chromosome count unchanged (Fig. 10.2).

Leaving the cycle: the quiescent stage (G0)

A surgeon can remove part of a person's liver and the organ grows back, yet beforehand its cells were hardly dividing at all. Where were they? Parked outside the cycle. Some cells, like the muscle cells of an adult heart, seem never to divide again; many others wait until the body needs them, for example to replace cells lost through injury or death.

The parking place is the quiescent stage, G0, which a cell enters by exiting the cycle from G1. Parked does not mean switched off: a G0 liver cell goes on making proteins, storing glycogen and cleaning the blood. It just stops multiplying until the organism's needs call it back.

Which cells can divide by mitosis? In plants, haploid and diploid cells alike, as their alternating generations show. Animals are stricter: mitosis is normally confined to diploid somatic (body) cells. The male honey bee breaks the rule, because it grows from an unfertilised egg and so is built entirely of haploid cells, all produced by mitosis.

10.2 M Phase

Biologists cut karyokinesis into four named stages, prophase, metaphase, anaphase and telophase, but the cell never pauses. The stages are like frames picked from a continuous film: one blurs into the next, and where you draw each line is partly a matter of convenience (Fig. 10.3).

Over that hour almost every part of the cell is reorganised. Chromatin packs into compact chromosomes, the nuclear envelope and several organelles break down, a spindle assembles, and then everything is rebuilt twice over, once in each daughter. Each daughter ends with exactly the parent's chromosome number, which is why mitosis is called an equational division.

10.2.1 Prophase

Think of two copies of a long necklace tangled together in a drawer: that is how each chromosome's DNA lies after S and G2. Both copies exist, but you cannot pick them out. Prophase begins when the cell starts to coil and fold this chromatin, and packing it tightly is also what untangles it. Each chromosome emerges as a short, thick body whose two chromatids can be told apart (Fig. 10.4).

Meanwhile a second preparation runs in the cytoplasm. The two centrosomes made in S drift apart towards opposite ends of the cell, each wrapped in a starburst of radiating microtubules called an aster. Spindle fibres grow between them, and the whole assembly, two asters plus the spindle, is the mitotic apparatus.

By the end of prophase, a cell seen under the microscope shows:

• compact chromosomes, each made of two chromatids joined at the centromere;
• two centrosomes moving to, or already at, opposite poles, each with its aster;
• no Golgi complex, endoplasmic reticulum, nucleolus or nuclear envelope.

10.2.2 Metaphase

If you want to photograph chromosomes, metaphase is your moment. They are as condensed as they will ever be, they lie spread out in the cytoplasm, and no nuclear envelope gets in the way, because its complete breakdown is exactly what marks the start of this stage. Their shape, size and number are easiest to study now.

Picture a tug-of-war on every chromosome. The ropes are spindle fibres and the handles are kinetochores, small discs on the surface of the centromere, one belonging to each sister chromatid and facing opposite ways. Once fibres from one pole grip one handle and fibres from the other pole grip the other, the pulls balance only when the chromosome sits midway between the poles. So the chromosomes settle, side by side, on a single plane across the spindle's equator: the metaphase plate.

So if every chromosome is tethered from both sides and the whole set sits in one line across the cell's middle, you are looking at metaphase.

10.2.3 Anaphase

The signal to start anaphase reaches every chromosome at once: all the centromeres split together. From that moment each former chromatid counts as a chromosome in its own right, a daughter chromosome, and it is towed to the pole its kinetochore faces. The kinetochore leads and the arms follow passively, bending each moving chromosome into a V or J whose point aims at the pole.

A quick test: two matching groups of chromosomes moving apart, with no nuclear envelopes yet, means anaphase.

10.2.4 Telophase

Telophase, the last stage of karyokinesis, runs prophase backwards. At each pole the chromosomes crowd together and unwind into chromatin, losing their separate outlines. A nuclear envelope is rebuilt around each crowd, giving two daughter nuclei, and the nucleolus, Golgi complex and endoplasmic reticulum, which vanished in prophase, return.

10.2.5 Cytokinesis

Karyokinesis leaves two nuclei inside one cell. The division is complete only when the cytoplasm is split too, by cytokinesis. Animal and plant cells do this in opposite directions (Fig. 10.5).

An animal cell divides the way you might cut a ball of dough with a loop of thread: it tightens a ring around its middle. The ring, made of actin and myosin filaments just under the flexible plasma membrane, contracts and draws the membrane inwards as a cleavage furrow, until the cell is pinched into two.

A plant cell, boxed in by a wall that barely stretches, cannot be squeezed in two. It partitions itself from within instead. A cell plate forms midway between the daughter nuclei and spreads sideways until its edges fuse with the old walls. This plate is the future middle lamella, the cementing layer between the walls of the two new neighbours.

Each daughter must also leave with its share of mitochondria and plastids. These organelles cannot be assembled from scratch: they grow and divide by themselves, so every new cell has to inherit some.

Cytokinesis does not always follow karyokinesis. When nuclei keep dividing but the cytoplasm does not, the result is a single mass of cytoplasm with many nuclei, a syncytium. You have tasted one: the water of a tender coconut is liquid endosperm, a cytoplasm with many free nuclei and no cell walls between them.

10.3 Significance of Mitosis

Mitosis, the equational division, mostly happens in diploid cells. It is not limited to them, though: haploid cells of certain lower plants, and of social insects such as bees, divide the same way. Wherever it happens its defining result is the same, two daughter cells with the parent's chromosome number and the same genetic information. That one property makes mitosis useful in several ways:

• Growth. A multicellular body grows chiefly by adding cells: a zygote becomes an embryo and then an adult through repeated mitosis.
• Restoring the nucleo-cytoplasmic ratio. As a cell grows, its cytoplasm increases while its nucleus does not keep pace, so one nucleus must control an ever larger volume. Dividing restores the balance between nucleus and cytoplasm (Fig. 10.6).
• Repair and replacement. The outermost skin cells, the cells lining the gut and blood cells wear out constantly, and mitosis supplies fresh ones; a wound heals the same way.
• Lifelong growth of plants. Meristems keep dividing by mitosis: the apical meristems at root and shoot tips lengthen the plant, and the lateral meristems (cambium) thicken it, so plants grow throughout their lives.

10.4 Meiosis

Sexual reproduction joins two gametes. If each gamete carried a full diploid set, the chromosome number would double every generation: 46 in your parents, 92 in you, 184 in your children. Nature avoids this with a special division that halves the chromosome number when gametes are made. That division is meiosis. It takes place only in specialised diploid cells and produces haploid daughter cells.

Picture a life cycle as a loop with two switches. One switch, meiosis, flips the cells from diploid to haploid; the other, fertilisation, flips them back. Plants and animals both throw the first switch while making gametes, during gametogenesis.11In flowering plants meiosis first makes haploid spores (microspores and megaspores), which then produce the gametes by mitosis. Class 12, Chapter 1 follows this in detail.

Meiosis in four numbers:

• 1 round of DNA replication, in the S phase before meiosis starts, so every chromosome enters meiosis I as two sister chromatids;
• 2 divisions in a row, meiosis I and meiosis II, with no replication between them;
• 2 homologues per pairing: maternal and paternal copies of each chromosome pair up and swap segments between their non-sister chromatids;
• 4 haploid cells at the end of meiosis II.

Each division runs through the familiar four stages, tagged I or II: prophase I, metaphase I, anaphase I and telophase I in the first division, and prophase II, metaphase II, anaphase II and telophase II in the second (Fig. 10.7).

10.4.1 Meiosis I

Prophase I is long and eventful, far more so than the prophase of mitosis. By watching what the chromosomes do, cytologists divide it into five sub-stages: leptotene, zygotene, pachytene, diplotene and diakinesis (Fig. 10.8). The Greek roots help you remember them: lepto- thin, zygo- yoked, pachy- thick, diplo- double, and dia-kinesis moving apart.

Leptotene. The nucleus fills with fine threads: chromosomes condensed just enough to be seen with a light microscope, and growing more compact as the stage goes on.

Zygotene. Each chromosome seeks out its partner, the homologue inherited from the other parent, and the two zip together side by side. The zipping is synapsis, and the zip itself, visible only with an electron microscope, is a ladder of proteins called the synaptonemal complex. A zipped pair counts as one unit, a bivalent; it is also called a tetrad, though its four chromatids only become easy to see in pachytene.

Pachytene. This is the long, busy stage; leptotene and zygotene are brief by comparison. The bivalent now plainly shows its four chromatids, two per homologue. Here and there small dense recombination nodules sit on the pair, and each marks a crossing over: one maternal and one paternal chromatid (non-sister chromatids) break at the same point and rejoin each other's pieces. An enzyme, recombinase, carries out this cut-and-rejoin. Because the swapped pieces carry different versions of genes, crossing over recombines the genetic material of the two homologues. The exchanges are finished by the end of pachytene, and the homologues are left tied together wherever one happened.

Diplotene. The protein zip comes undone and the two homologues start to drift apart. They cannot separate completely, because they are still tied wherever crossing over occurred; each tie shows up as an X, a chiasma (plural chiasmata). Diplotene is not always brief: in the egg-forming cells (oocytes) of some vertebrates it stretches over months or even years. A human oocyte reaches diplotene before the girl is born and stays there until shortly before that egg is ovulated, many years later.

Diakinesis. Now the chiasmata slip along the arms towards the chromosome ends, a movement called terminalisation, while the chromosomes reach maximum compaction. The cell clears the way for division: the nucleolus disappears, the nuclear envelope breaks down and a meiotic spindle forms to pull the homologues apart. Diakinesis therefore runs straight into metaphase I.

Metaphase I. The bivalents line up on the equatorial plate. Spindle microtubules coming from the two poles attach to the kinetochores of the two homologous chromosomes, one homologue to each pole (Fig. 10.9). Compare mitosis, where it is the two sister chromatids of one chromosome that are tied to opposite poles.

Anaphase I. Now whole homologues are pulled apart, one of each pair to each pole. No centromere splits, so every departing chromosome keeps both its sister chromatids, and the chromosome count at each pole is halved. This is the step that makes meiosis a reduction division.

Telophase I. Two new nuclei form, each with its nucleolus, and the cell usually divides to give a two-celled dyad. The chromosomes relax a little, but they stay far more compact than in an interphase nucleus.

Between the two divisions comes interkinesis, usually brief. Unlike interphase it has no S phase, so the DNA is not copied again, and this is what lets meiosis II halve the DNA content once more. Prophase II, which follows, is short and simple compared with prophase I.

10.4.2 Meiosis II

Meiosis II is a mitosis-like division of both cells of the dyad (Fig. 10.10):

• Prophase II. There is hardly a pause: prophase II starts right after the first cytokinesis, often while the chromosomes are still partly condensed. They compact fully again, and the nuclear membrane has vanished by the end of this stage.
• Metaphase II. The chromosomes gather at the equator of a new spindle, and the kinetochore of each sister chromatid is captured by microtubules from the pole it faces.
• Anaphase II. All the centromeres split at once, releasing the sister chromatids. Each is pulled to its pole as the microtubules attached to its kinetochore shorten.
• Telophase II. Nuclear envelopes form around the four groups of chromosomes, and cytokinesis turns the two cells into a tetrad of four haploid cells.

10.5 Significance of Meiosis

Here is a puzzle. How can a division that halves the chromosome number be the reason a species' chromosome number never changes? Add fertilisation and the puzzle resolves: n from the egg plus n from the sperm restores 2n in every zygote. Meiosis is therefore exactly what keeps the chromosome number constant across the generations of a sexually reproducing species; without it the number would double each time.

Meiosis also shuffles genes, so each generation of a population is more varied than straight copying would make it. Crossing over in pachytene creates chromatids with new mixtures of maternal and paternal genes. At metaphase I each bivalent also lines up independently of the others, so a gamete may receive any mixture of maternal and paternal homologues (Fig. 10.12). Random fertilisation then brings together two such gametes. Variation is the raw material of evolution; Class 12, Chapter 4 explores its genetics.