Meiosis describes the process of cell division by which gametes are made. In this process, we begin with a cell with double the normal amount of DNA, and end up with 4 non-identical haploid daughter gametes after two divisions.
There are six stages within each of the divisions, namely prophase, prometaphase, metaphase, anaphase, telophase and cytokinesis. In this article, we will look at the stages of meiosis and consider its significance in disease.
In meiosis I, homologous chromosomes are separated into two cells such that there is one chromosome (consisting of two chromatids) per chromosome pair in each daughter cell, i.e. two chromosomes total.
Prior to prophase, chromosomes replicate to form sister chromatids. There are initially four chromatids (c) and two chromosomes (n) for each of the 23 chromosome pairs (4c, 2n). The nuclear envelope disintegrates and the chromosomes begin to condense. Spindle fibres appear which are important for the successful division of the chromosomes.
To further increase genetic diversity, homologous chromosomes exchange small parts of themselves, such that one chromosome contains both maternal and paternal DNA. This process is known as crossing over, and the points at which this occurs on a chromosome are referred to as chiasmata.
Spindle fibres attach to the chromosomes at points along the chromosomes called centromeres. While this is happening, the chromosomes continue to condense.
Maternal and paternal versions of the same chromosome (homologous chromosomes) align along the equator of the cell. A process called independent assortment occurs – this is when maternal and paternal chromosomes line up and randomly align themselves on either side of the equator. This in turn determines which gamete chromosomes are allocated to, which leads to genetic diversity among offspring.
Here, each of the homologous chromosomes is pulled towards opposite poles of the cell as the spindle fibres retract. This equally divides the DNA between the two cells which will be formed.
Telophase I and Cytokinesis I
During telophase I, the nuclear envelope reforms and spindle fibres disappear. In cytokinesis I, the cytoplasm and cell divide resulting in two cells that are technically haploid – there is one chromosome and two chromatids for each chromosome (2c, n).
Prophase II and Prometaphase II
These stages are identical to their counterparts in meiosis I.
In metaphase II, chromosomes line up in single file along the equator of the cell. This is in contrast to metaphase I, where chromosomes line up in homologous pairs.
Next, sister chromatids are pulled to opposite poles of the equator.
This stage is the same as telophase I.
Again, the cytoplasm and cell divide producing 2 non-identical haploid daughter cells. As this is happening in both cells produced by meiosis I, the net product is 4 non-identical haploid daughter cells, each containing one chromosome consisting of one chromatid (1c, 1n). These are fully formed gametes.
Clinical Relevance – Chromosomal abnormalities
Chromosome abnormalities occur in approximately 0.6% of live births, however, they are common in pregnancy losses. Errors in the process of meiosis can lead to abnormalities in either chromosome number or structure.
Abnormalities in chromosome number include aneuploidy, where there is loss or gain of a whole chromosome. This is often due to nondisjunction where there is failed separation of chromosomes during anaphase, so either whole chromosomes (error occurring in meiosis I) or chromatids (error occurring in meiosis II) move to the same pole of the cell. This leaves one gamete short of some genetic information, and the other with additional genetic information.
- Monosomy – one copy of a chromosome, e.g. Turner syndrome (45, X)
- Trisomy – three copies of a chromosome, e.g. Edward’s syndrome (trisomy 18)
Abnormalities in chromosome structure are often due to translocations, where there is an exchange of material between two chromosomes, resulting in an abnormal rearrangement. If there is no gain or loss of genetic material, this is a balanced translocation, however, if the exchange of chromosomal material results in extra or missing genes in a daughter cell, it is known as unbalanced and can have clinical effects.
There are two types of chromosomal translocation. Reciprocal translocations take place when the chromosomes break within the arms of the chromosome and Robertsonian translocations take place when whole chromosomes join end to end.
Anaphase lag can occur when chromosomes are left behind due to defects in the spindle fibres or attachment to chromosomes. This differs from non-disjunction as neither cell receives the chromosome/chromatid, leaving both daughter cells short of genetic information
Clinical Relevance – Down’s syndrome
Down’s syndrome occurs when there is an extra copy of chromosome 21 (trisomy 21). Typical signs and symptoms include muscular hypotonia, a single palmar crease, protruding tongue, congenital heart malformations and distinguishable facies.
95% of cases occur when there are three separate copies of chromosome 21 due to nondisjunction. 4% of cases are secondary to Robertsonian translocation, where a chromosome acquires a large chunk of chromosome 21, effectively leading to three copies. The remaining 1% of cases are due to post-zygotic mosaicism, where non-disjunction occurs in early embryonic development, meaning some cells have 46 chromosomes as usual, while others have trisomy 21. This generally leads to milder symptoms due to the presence of normal cells.