The process by which a cell distributes its genetic material (DNA) and cytoplasm to daughter cells.
In higher organisms including humans, there are two types of cell division, mitosis and meiosis. Strictly speaking, mitosis and meiosis refer to division of the DNA and associated materials in the nucleus of the cell. In mitosis, the cells produced by division have exactly the same genetic information as the original cell, while in meiosis the cells produced by division have only half the genetic
Mitosis produces two daughter cells, each of which has the same genetic information as the parent cell. The entire process includes a series of precise steps to insure that the genetic material is accurately duplicated and distributed. The life of a cell is generally made up of two parts, interphase and mitosis. During interphase, DNA synthesis occurs. Since the process uses the original DNA as a template, the copy is exact (or nearly exact if mutations occur). After a pause, the cell then enters mitosis. Although the lifespan of a cell varies in length depending on the cell type, mitosis itself usually takes about one to two hours and involves four stages: prophase, metaphase, anaphase, and telophase.
PROPHASE. During prophase, the chromosomes, which contain the DNA, condense in length and become visible under a microscope. Humans have 23 chromosome pairs, for a total of 46 chromosomes. Since DNA duplication has already occurred, each of the 46 chromosomes at this stage is present in two copies referred to as sister chromatids. The two sister chromatids of a pair are attached to each other at a point called the centromere. As the chromosomes condense, the membrane surrounding the nucleus disappears, and fibers appear, which come together to form a spindle within the cell. The spindle has two opposite poles and a mid-section, the equatorial plate.
METAPHASE. At the beginning of metaphase, the chromosomes line up individually on the equatorial plate. Fibers emanating from the poles of the spindle attach to the centromeres of the sister chromatids. One member of each pair of sister chromatids is attached to a spindle fiber that radiates from one pole, and the other is attached to a fiber that radiates from the opposite pole.
ANAPHASE. After all chromosomes (92 sister chromatids in 46 pairs) have aligned on the equatorial plane of the spindle, the centromere of each chromosome splits, and the fibers begin to contract. One sister chromatid of each pair is pulled to one pole of the spindle and the other is pulled to the opposite pole.
TELOPHASE. Separate membranes form around the chromosome sets at each pole to form two nuclei. The chromosomes elongate and the spindle disappears. Cytokinesis then occurs, resulting in two daughter cells each with 46 chromosomes and roughly half the cytoplasm of the parent cell.
Function and role in human health
Mitosis is the process by which a single human zygote (fertilized egg cell) becomes a complex organism consisting of over 100 trillion cells. During the lifetime of an individual, mitosis continues. In some tissues such as epithelium (skin, mucous membranes), mitosis actively occurs to replace cells and repair damage. Other cell types such as nerve cells do not readily undergo mitosis after a certain point in development. Thus the capacity for mitosis is programmed into each cell type and is cell- specific. In addition, there are many molecules within the body that can influence cell division. Scientists are just beginning to learn about some of these and their possible roles in human health. For example, cancer occurs when the normal pattern of cell division within a tissue or organ is disrupted, and the cells begin to repeatedly undergo mitosis. Changes within the cell as well as external influences can play a part in disrupting the normal control of mitosis.
Meiosis is a special type of cell division that, in higher organisms, occurs only in cells of the ovaries or testes. Within these organs, cells destined to become eggs and sperm undergo meiosis in order to halve the amount of DNA that will be packaged into an egg or sperm. As with all the other cells in the body, these precursor cells are diploid; that is, they have the full complement of 46 chromosomes (23 pairs). Whereas mitosis creates two diploid cells from one existing diploid cell, meiosis results in eggs and sperm that have only one member of each pair of chromosome. Thus these cells, collectively known as germ cells, have only 23 chromosomes and are said to be haploid. At fertilization, the union of one egg and one sperm produces a diploid zygote (fertilized egg) with 46 chromosomes, half from the mother and half from the father. This zygote then begins the many mitotic divisions that will take it from a single cell to a complex, fully differentiated organism.
The steps in meiosis are similar in many ways to those in mitosis, but there are several important differences. One obvious distinction is that, unlike mitosis which includes only one division of the nucleus and cytoplasm, meiosis is actually composed of two divisions, meiosis I and meiosis II. As in a mitotic division, DNA duplication occurs during interphase before meiosis so that the cells begin meiosis I with double the diploid amount of DNA (92 sister chromatids).
MEIOSIS I PROPHASE. Prophase of meiosis I (prophase I) includes several significant features. As the chromosomes condense, chromosome pairing occurs. This is an important phenomenon that occurs only during
meiosis. Higher organisms receive half of their genetic material from their mother and half from their father; that is, one set of chromosomes is maternal in origin and the other set is paternal. During interphase of a cell cycle, as well as during mitotic divisions, these various chromosomes from the maternal and paternal sets do not associate in pairs. Pairing only occurs in prophase of meiosis I. This pairing brings the same chromosome from the mother and father together in close association. This pairing is essential for the important step that happens next.
A process of crossing over occurs between the maternal and paternal member of each chromosome pair. These crossover points, which can be seen through the microscope, are the places where maternal and paternal chromosomes have exchanged sections of genetic material in a process known as recombination. This essential step occurs during meiosis and serves to recombine the genetic material an individual received from their mother and father. That individual can then pass on new combinations of the genes from their parents to their offspring. This greatly increases the possible combinations of genetic traits and helps create diversity in the offspring. At the end of prophase, recombination is complete and the chromosome pairs, still attached at their cross-over points, move to the equatorial plate of the spindle that is beginning to form.
In females the process of meiosis begins while the individual herself is still an embryo. The eggs within that early embryo complete prophase I up to a certain point and then go into an arrested state. Eggs only begin to be released from that arrest many years later after a woman has reached puberty. Each month as one egg is ovulated (released from the ovary), meiosis resumes.
MEIOSIS I METAPHASE. During metaphase I, the 23 chromosome pairs line up on the equatorial plate of the spindle with one member of each pair attached by a spindle fiber to one pole and the other member attached to the other pole. At this point the two members of a pair (each of which is itself composed of a pair of sister chromatids) are being held together only at the anchor points created by the cross-overs. When all chromosome pairs are prop- erly aligned on the equatorial plate of the spindle, the anchors release and anaphase I begins.
MEIOSIS I ANAPHASE. During this stage, the two members of a chromosome pair travel to opposite spindle poles. Unlike anaphase of mitosis, the centromeres do not separate. Thus, each chromosome at a pole is composed of a pair of sister chromatids attached at their centromeres. An important point to understand is that the pairs of chromosomes do not line up on the spindle with all of the individual's mother's chromosomes pointing toward one pole and the father's pointing to the other. The alignment is random, so the function of meiosis I is similar to the shuffling of a deck of cards before dealing a hand. The half set of 23 chromosomes that collects at one spindle pole during anaphase will have chromosomes, and thus genetic information, from both the individual's mother and father. This is another way in which
meiosis increases diversity in the offspring. When the Austrian monk Gregor Mendel put forth his principles of heredity in 1865, the process of meiosis had not been discovered. However, scientists later came to realize that the inheritance pattern Mendel described for specific traits such as color and shape in the garden pea, were due to the events of the first meiotic division.
MEIOSIS I TELOPHASE. At the poles, a separate nuclear membrane forms around each haploid chromosome set and cytokinesis occurs, resulting into two daughter cells. In females, cytokinesis produces one large cell with the bulk of the cytoplasm, and one very small cell, the first polar body. The larger cell proceeds to meiosis II. In males, cytoplasmic division is equal and both cells enter meiosis II. Because meiosis I has reduced the diploid number of 46 chromosomes to 23, meiosis I is often referred to as the reduction division.
MEIOSIS II INTERPHASE. Unlike in mitosis, there is no further DNA duplication and interphase is brief.
MEIOSIS II PROPHASE. The nuclear membrane breaks down and a new spindle begins to form.
MEIOSIS II METAPHASE. The haploid set of 23 chromosomes, each consisting of a pair of sister chromatids, moves to the equatorial plate of the spindle. Fibers from the two poles attach at each centromere pair and exert tension to align the chromosomes.
MEIOSIS II ANAPHASE. The centromeres separate, and the sister chromatids are pulled to opposite poles. In this regard meiosis II is very similar to mitosis. In females, anaphase II is triggered by the sperm entering the recently ovulated egg.
MEIOSIS II TELOPHASE. The chromosomes begin to de-condense, a nuclear membrane forms around each set, and cytokinesis occurs. In sperm, cytokinesis is again equal and the result is the production of four haploid spermatids, which will go through a process of maturation to become sperm. In males, there is no arrest of meiosis and the entire meiotic process takes about 60 days. In females, meiosis II produces a small second polar body containing one set of chromosomes and a small amount of cytoplasm. The majority of the cytoplasm together with the other set of chromosomes comprises the ovum (mature egg). Since a sperm has already penetrated the envelope of the egg, all that remains is for the haploid chromosome sets from the egg and sperm to merge to produce the diploid zygote.
Common diseases and disorders
In humans, errors in chromosome division occur frequently during meiosis. Although these errors can take place either during the formation of the egg or the sperm, most errors occur during meiosis in the female for reasons that are not yet clearly understood. If mistakes occur during meiosis, eggs and sperm can be formed with either too many or too few chromosome. Fertilization then results in a fertilized egg than has less than or more than 46 chromosomes, a situation with major health consequences. For example, roughly 20% of all clinically recognized pregnancies result in miscarriage. Half of these are due to an extra or missing chromosome(s) in the developing embryo. Among live births, one in 150 infants has some type of chromosome abnormality. One of the more common is Down syndrome. Most cases of
Amniocentesis—A procedure performed around the fourth month of pregnancy in which a needle is inserted through a woman's abdomen into her uterus to draw out a small sample of the amniotic fluid from around the baby. Fetal cells in the fluid can be used to check the chromosome make-up of the baby.
Chorionic villus sampling (CVS)—A procedure used for prenatal diagnosis at eight to 10 weeks gestation. Under ultrasound guidance a needle is inserted either through the mother's vagina or abdominal wall and a sample of cells is collected from around the early embryo. These cells can be used to study the chromosomes of the fetus.
Chromosomes—Structures in the nucleus of a cell that contain a thread of DNA containing the genetic information (genes). Humans have 46 chromosomes in 23 pairs.
Cytoplasm—The portion of the cell that surrounds the nucleus.
DNA—Deoxyribonucleic acid, the molecule that encodes the genes.
Genetic counselor—An individual, usually with an advanced degree and board certification, who specializes in assessing genetic risk and informing patients about these risks and the options for dealing with them.
Geneticist—A individual with an advanced degree (MS, MD, PhD) in genetics. Human geneticists and medical geneticists specialize in genetic issues pertaining to humans. Many geneticists are certified by specialty boards.
Nucleus—The membrane-bound body within a cell that contains the chromosomes.
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Sallie Boineau Freeman, PhD