Genetics, Meiosis

Cellular

The genome is encoded by the chemical sequence of DNA nucleotides within human cells. If stretched from end to end, the DNA in 1 cell would span about 3 meters. To fit into each cell, DNA is condensed by proteins to create chromatin, a complex of DNA and proteins. Somatic human cells contain 23 paired chromosomes, or 46 total chromosomes. The number 46 is considered the diploid number (2n), whereas 23 is considered the haploid number (1n), or half the diploid number.[6][7]

Function

Meiosis is important for generating genetic diversity within a species. Meiosis accomplishes genomic diversity primarily through 2 processes: independent assortment and crossing over (recombination). The Law of Independent Assortment states that the random orientation of homologous chromosome pairs during metaphase 1 allows for the production of gametes with many different assortments of homologous chromosomes. For example, tetrads containing chromosomes 1A and 1B, and 2A and 2B, can produce 4 different combinations in daughter cells: 1A2A, 1A2B, 1B2A, and 1B2B. With 46 chromosomes in the human diploid cell, about 8 million different variations can be produced. Crossing over is a phenomenon that occurs during prophase 1. When homologous chromosomes come together to form tetrads, the arms of the chromatids can exchange segments at random, creating many more possibilities for genetic variation in gametes.

Mechanism

The cell cycle has 2 parts: interphase and mitosis or meiosis. Interphase can be further subdivided into growth 1 (G1), synthesis (S), and growth 2 (G2). During the G phases, the cell grows by producing various proteins, and during the S phase, DNA is replicated so that each chromosome contains 2 identical sister chromatids (c). Mitosis contains 4 phases: prophase, metaphase, anaphase, and telophase.

Mitosis

• Prophase: The nuclear envelope breaks down. The chromatin condenses into chromosomes.
• Metaphase: The chromosomes line up along the metaphase plate. Microtubules originating from the centrosomes at the 2 opposite poles of the cell attach to the kinetochores of each chromosome.
• Anaphase: Chromatids separate and are pulled by microtubules to opposite ends of the cell.
• Telophase:  The chromosomes gather at the poles of the cell, and the cell divides through cytokinesis, forming 2 daughter cells. The nuclear envelope reappears, the spindle apparatus disappears, and the chromosomes decondense back into chromatin.

The cell can now enter interphase, during which it grows and replicates its DNA in preparation for division. Meiosis proceeds through 2 rounds of cell division, with specialized mechanisms that ultimately produce haploid cells rather than diploid cells. In sperm cells, the male gametes, meiosis proceeds in the following manner:

Meiosis I

• Prophase I: The nuclear envelope breaks down. The chromatin condenses into chromosomes. Homologous chromosomes containing the 2 chromatids come together to form tetrads, joining at their centromeres (2n 4c). Crossing over occurs during this phase, creating genetic variation.
• Metaphase I: The tetrads line up along the metaphase plate. Microtubules originating from the centrosomes at the 2 opposite poles of the cell attach to the kinetochores of each chromosome.
• Anaphase I: Homologous chromosomes are separated by the microtubules to opposite poles of the cell.
• Telophase I: The chromosomes gather at the poles of the cell, and the cell divides through cytokinesis, forming 2 daughter cells (1n 2c). The nuclear envelope reappears, the spindle apparatus disappears, and the chromosomes decondense back into chromatin.

Interkinesis/Interphase II 

A brief pause occurs between each round of meiosis, allowing the cell to replenish proteins; however, no S phase occurs.

Meiosis II

• Prophase II: In each of the daughter cells, a new spindle apparatus forms, the nuclear envelope breaks down, and the chromatin condenses into chromosomes again.
• Metaphase II: The chromosomes line up along the metaphase plate. Microtubules originating from the centrosomes at the 2 opposite poles of the cell attach to the kinetochores of each chromosome.
• Anaphase II: Sister chromatids separate and are pulled by the microtubules to opposite poles of the cell.
• Telophase II: The chromosomes gather at the 2 poles of the cell, and the cell divides through cytokinesis, forming 2 daughter cells (1n 1c) from each of the 2 cells from meiosis I. The nuclear envelope reappears, the spindle apparatus disappears, and the chromosomes decondense back into chromatin.

In egg cells, the female gametes, meiosis follows the same general phases with only a slight variation. During telophase I, the cytoplasm divides unequally, creating a larger daughter cell and a smaller polar body. The polar body and the daughter cell both then enter meiosis II. In telophase II, the cytoplasm of the daughter cell again divides unequally and creates a daughter cell and another polar body. In addition, the polar body from meiosis I divides, forming 2 smaller polar bodies. After meiosis is completed, 1 daughter cell (1n, 1c) and 3 polar bodies (1n, 1c) remain. The polar bodies disintegrate because they lack sufficient cytoplasm and proteins to survive as gametes.

Clinical Significance

Clinically, errors in meiosis can create many potentially life-threatening outcomes. The most common error of meiosis is nondisjunction, which occurs when chromatids fail to separate during either anaphase I or anaphase II, creating imbalances in the number of chromosomes in each daughter cell. Most imbalances are incompatible with life, but some can result in viable offspring with a spectrum of developmental disorders. These medical conditions include Down syndrome, Patau syndrome, Edwards syndrome, Klinefelter syndrome, Turner syndrome, triple X syndrome, and XYY syndrome.