Why Brothers and Sisters Never Look Exactly Alike

If eggs and sperm were made by mitosis, each would carry a full set of chromosomes, and the number would double every generation. Meiosis prevents that by halving the chromosome number, and along the way it shuffles genes into new combinations.

This part covers the substages of prophase I, the rest of meiosis I, meiosis II compared with mitosis, and the significance of meiosis.

Prophase I is a long, complex stage in which chromosomes condense, homologous chromosomes pair up through a synaptonemal complex to form bivalents, non-sister chromatids exchange segments by crossing over, and the homologues then separate except at X-shaped chiasmata.

The five substages:

- Leptotene — chromosomes gradually become visible as they condense
- Zygotene — homologous chromosomes start pairing, called synapsis, helped by a synaptonemal complex; each pair is a bivalent, or tetrad
- Pachytene — the four chromatids of each bivalent are clear; recombination nodules mark the sites where crossing over takes place between non-sister chromatids of homologous chromosomes, catalysed by the enzyme recombinase
- Diplotene — the synaptonemal complex dissolves and homologues begin to separate, except at the crossover points, which appear as X-shaped chiasmata
- Diakinesis — chiasmata terminalise, chromosomes are fully condensed, the spindle assembles, and the nucleolus and nuclear envelope disappear

Worked example — count the parts. A bivalent has two homologous chromosomes and four chromatids, so a cell with $10$ bivalents shows $20$ chromosomes and $40$ chromatids at pachytene.

An everyday example. Two friends swapping a few pages between their copies of the same textbook end up with mixed copies — like non-sister chromatids exchanging segments.

The substance. Synapsis begins in zygotene, but crossing over happens in pachytene — the chiasmata of diplotene are its visible result.

In metaphase I bivalents line up at the equator, in anaphase I homologous chromosomes separate to opposite poles while sister chromatids stay joined, and in telophase I two nuclei form, usually followed by cytokinesis into a dyad of cells.

Metaphase I:

- Bivalents align on the equatorial plate
- Spindle fibres from opposite poles attach to the kinetochores of the two homologous chromosomes of each pair

Anaphase I:

- Homologous chromosomes separate and move to opposite poles
- Sister chromatids remain attached at their centromeres

Telophase I:

- The nuclear membrane and nucleolus reappear
- Cytokinesis follows, giving a dyad of cells

Interkinesis. The short gap between the two meiotic divisions. There is no DNA replication in this gap.

Worked example — follow the numbers. A cell with $2n=20$ enters meiosis I. In anaphase I, each pole receives $10$ chromosomes, each still made of two chromatids — so each cell of the dyad has $n=10$.

An everyday example. Partners standing side by side for a three-legged race are then sent to opposite ends of the ground — one of each pair to each end, just as homologues part in anaphase I.

The substance. Meiosis I is the reductional division — the chromosome number halves here, not in meiosis II.

Meiosis II closely resembles mitosis — sister chromatids separate to opposite poles — but it starts from haploid cells, follows no fresh DNA replication, separates chromatids that are no longer identical after crossing over, and ends with four haploid cells instead of two diploid ones.

Stages of meiosis II:

- Prophase II — the nuclear membrane disappears and chromosomes become compact again
- Metaphase II — chromosomes line up at the equator; spindle fibres from opposite poles attach to the kinetochores of sister chromatids
- Anaphase II — the centromere of each chromosome splits, and the chromatids move to opposite poles
- Telophase II — two groups of chromosomes are enclosed by nuclear envelopes; cytokinesis follows, giving a tetrad of cells

Meiosis II versus mitosis:

- Starting cell: haploid versus diploid
- DNA replication just before: none versus in S phase
- Chromatids separated: not identical, because of crossing over, versus identical
- Final outcome: four haploid cells from the whole of meiosis versus two diploid cells

An everyday example. Dealing a stack of paired photocopies into two piles, one copy to each, is like anaphase II separating sister chromatids.

The substance. Meiosis II does not change the chromosome number; like mitosis, it is equational.

Meiosis halves the chromosome number to form haploid cells, so fertilisation restores the diploid number in each generation, and through crossing over and the random sorting of homologues it produces genetic variation, the raw material for evolution.

Constant chromosome number:

$$\text{parent }(2n)\stackrel{\text{meiosis}}{\to }\text{gametes }(n)\stackrel{\text{fertilisation}}{\to }\text{zygote }(2n)$$

Worked example — humans. Body cells have $46$ chromosomes and gametes have $23$, so the zygote has $23+23=46$. Without meiosis, the next generation would have $46+46=92$.

Sources of variation:

- Crossing over in pachytene creates new combinations of genes on a chromosome
- Random alignment of bivalents at metaphase I sends maternal and paternal chromosomes to the poles in many combinations

With $n$ pairs, random sorting alone gives $2^n$ combinations; for humans, $2^{23}=8388608$, about $8.4$ million, before crossing over adds more.

An everyday example. Brothers and sisters born to the same parents look different from one another, because each received a different mix of the parents' chromosomes.

The substance. Variation among offspring is important for evolution, giving natural selection differences to act on.