12.3: Meiosis

The twenty-three chromosome pairs in humans accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.

Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.

In contrast, meiosis is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.

Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.

Meiosis

Meiosis is composed of two distinctive cell divisions, meiosis I and meiosis II, which are found only in the germline. Through these two divisions, haploid gametes are formed from diploid somatic cells. There is only one replication of the DNA, but there are two divisions of the chromosomes. The first division differs from the second in that there is pairing and recombination between homologous chromosomes resulting in variation in the genetic makeup of the gametes. Segregation of the homologues occurs during the first meiotic (reductional) division, reducing the forty-six chromosomes to twenty-three, one from each homologous pair. The second (equational) division is similar to mitosis with segregation of sister chromatids into daughter cells (figure 12.10).

Figure 12.10: Overview of meiosis.

Meiosis I: Reductional division

Before meiosis, gametic stem cells replicate through mitosis. At the very beginning of meiosis, the last G₁ phase of the diploid stem cells is followed by chromosome replication during S phase and G₂, ending the last somatic interphase. Thus, each cell enters meiosis with two copies of the diploid genome (2n, 2c). At this point, the spermatogonium (male somatic cell) enlarges to become a primary spermatocyte, and the oogonium (female somatic cell) enlarges to become a primary oocyte.

These cells then enter prophase I, which is subdivided into five stages: leptotene, zygotene, pachytene, diplotene, and diakinesis. In female meiosis, there is an additional stage following diplotene called dictyotene in which the oocyte remains from early fetal gestation until ovulation when diakinesis occurs.

Prophase I

During prophase I, homologous chromosomes pair and undergo recombination through crossing over. This is visualized by the presence of X-shaped connections between homologues, called chiasmata, as the homologues begin to repel each other. These chiasmata will aid in the proper segregation of the chromosomes and become more prominent during diplotene. This is where the synaptoneal complex dissolves, allowing for chromosomal condensation to continue and for the repulsion of homologous chromosomes. The separation of the homologous chromosomes causes the chiasmata to appear. Individual chromatids can be visualized during this stage. (The dictyotene stage is unique to female meiosis in which there is a decondensation of chromosomal bivalents. The oocyte remains in this state for many years until follicle maturation and ovulation.)

At diakinesis, chromosomal condensation is completed. The chiasmata on each arm of the chromosomes move distally toward the telomeres. Each bivalent contains four chromatids, and pairs of sister chromatids are linked at the centromeres.

Metaphase I

The spindle forms, and the nuclear membrane disappears. Bivalents align on the metaphase plate still held together by the chiasmata. The centromeres of the two homologous chromosomes are separate, aligning on either side of the equatorial plate.

Anaphase I

Homologous chromosomes separate from each other by final terminalization of the chiasmata. They move to opposite poles, pulled by the centromere, which is attached to spindle fibers.

Telophase I

The chromosomes reach the poles, a nuclear membrane is formed, and cell division occurs. In male meiosis, the cytoplasm is divided equally, and the two resulting cells become secondary spermatocytes. In female meiosis, the division is unequal; most of the cytoplasm is retained in the secondary oocyte, while very little is retained by the first polar body. This period is very brief, and chromosomes move immediately to the second meiotic division. Each cell at this stage is haploid (1n) but with each chromosome formed of sister chromatids (2c). The sister chromatids may be unique due to recombination during the two homologues in prophase I.

Meiosis II: Equational division

This division is similar to mitosis in that individual chromosomes align on the metaphase plate, and sister chromatids separate and move to opposite poles at anaphase. The single copy (1c) of each chromosome is represented by one sister chromatid in the spermatids or mature ova.

Male meiosis

In humans, the male is the heterogametic sex, producing two kinds of normal sperm: 23,X and 23,Y. Spermatogenesis is a constant event beginning at puberty and continuing throughout life to produce four functional spermatids from each primary gametocyte. At puberty, the number of spermatogonia (diploid stem cells) increases. These develop into primary spermatocytes after several mitotic divisions. Each primary spermatocyte undergoes the first meiotic division to become two secondary spermatocytes. These cells then undergo the second meiotic division to become four spermatids of equal size with a haploid set of chromosomes. Spermiogenesis then transforms the spermatids into mature spermatozoa by elimination of the cytoplasm, elongation of the head of the sperm, and formation of a tail. The entire process from the enlargement of the spermatogonium to formation of the mature spermatozoa takes approximately sixty-four days.

Female meiosis

This is in contrast to meiosis in females, which begins before birth and produces only a single type of normal ovum: 23,X. The precursors to the germ cells are oogonia; these increase in number through mitosis, reaching a maximum number of approximately 7 million. Each individual oogonium enlarges to form a primary oocyte, which becomes surrounded by ovarian stromal cells to form a primary follicle. The vast majority of primary oocytes are formed during the third and fourth months of fetal life.

The primary oocyte begins the first meiotic division to become a secondary oocyte with the extrusion of a small polar body as the follicle matures and completes metaphase I with expulsion from the mature follicle at ovulation. The secondary oocyte does not complete the second meiotic division until fertilization, when a second polar body is extruded to form a mature ovum with a haploid set of chromosomes. Thus, each primary oocyte produces one functional gamete, the mature ovum, and three polar bodies. A nuclear membrane forms a pronucleus around the haploid set of maternal chromosomes, while a second pronucleus forms from the haploid set of chromosomes from the sperm head. These two pronuclei then fuse to begin the first mitotic division.

Meiotic pairing

Homologous pairing is unique to meiosis and plays two important roles: genetic recombination and chromosomal stabilization. While it has long been believed that the former is the most important, the latter is now accepted as the primary significance of meiotic recombination. During meiosis I, the pairing of homologues facilitates recombination, which is initiated by programed double-stranded breaks occurring at synaptic initiation sites (SISs). A subset of these breaks will resolve into the formation of the synaptonemal complex. When pairing is completed, synapsis occurs between the homologues, which completes the crossing over event. Each crossover event forms chasmata, which play an analogous role to the centromere and stabilize the maternal and paternal chromosomes. The stabilization of the metaphase chromosomes using this mechanism is key to normal chromosomal alignment and maintenance of an intact genome. Without recombination, the total number of unique gametic combinations of genes for each parent would be just over 8 million. However, crossing over greatly increases the total number of possible gene combinations such that the likelihood of either parent producing identical gametes is vanishingly small.

References and resources

Text

Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.

Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.

Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.

Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics  in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.

Figures

Grey, Kindred, Figure 12.10 Overview of Meiosis. 2021. https://archive.org/details/12.10_202109. CC BY 4.0. Added Meiosis Stages by Ali Zifan. CC BY 4.0. From Wikimedia Commons.