Asexual vs. Sexual Reproduction (Genetics & Inherited Conditions)
A cell’s genetic blueprint is encoded in genes written in the four-letter alphabet of DNA, which stands for the four nucleotides that make up the strands of DNA: guanine (G), adenine (A), thymine (T), and cytosine (C). Reproduction of this blueprint is an essential property of life. Prokaryotes (cells without nuclei) contain a single chromosome in the form of a circular double helix. They replicate their DNA and reproduce asexually by binary fission. Eukaryotic cells, with two or more pairs of linear, homologous chromosomes in a nucleus, replicate their DNA and reproduce asexually by mitosis. In sexual reproduction in higher organisms, special cells called germ cells are set aside to form gametes by meiosis. During meiosis, the germ cells duplicate their chromosomes and separate the homologs into gametes. After mitosis, new cells have a copy of all of the chromosomes originally present in the parent cell; after meiosis, gametes (sperm or egg) contain only one of each homologous chromosome originally present in the parent cell. Though their chromosomal outcomes are quite different, the cellular events of mitosis and meiosis share many similar features, discussed below mostly in the context of mitosis. The focus here is on when cells replicate their DNA, when they physically divide, and how they partition duplicate sets of genetic information into progeny cells.
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Binary Fission vs. Meiosis, Mitosis, and Cytokinesis (Genetics & Inherited Conditions)
During binary fission, which occurs in prokaryotic cells (cells that have no nucleus—primary bacteria), these small cells grow larger, become pinched in the middle, and eventually produce two new cells. A specific base sequence in the circular bacterial DNA molecule attaches to the cell membrane. When this sequence replicates during DNA synthesis it also attaches to the cell membrane, but on the opposite side of the cell. As the bacterial cell grows and divides, the two DNA attachment points become separated into the progeny cells, ensuring that each gets a copy of the original circular DNA molecule. DNA replication and cell division in prokaryotes are therefore simultaneous processes.
Mitosis (and meiosis) and cytokinesis, by contrast, are processes well separated in time from DNA replication. When first observed in the microscope in the 1880’s, mitosis seemed to be a busy time in the life of a cell. During prophase (the initial phase of mitosis), nuclei seem to disintegrate in a matter of minutes at the same time that chromosomes take shape from nondescript nuclear substance. Spindle fibers form at opposite poles and grow toward the center of the cell. After about thirty minutes, cells are in metaphase. The spindle fibers extend across the cell, attaching to fully formed chromosomes lined up at the metaphase plate in the middle of the cell. Each chromosome is actually composed of two...
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The Cell CycleCell cyclecell division (Genetics & Inherited Conditions)
Early histologists studying mitosis noted that it often took cells about twenty hours to double, implying a long period between successive cell divisions. This period was called interphase, meaning simply “between” the mitotic phases. An interphase also separates the first meiotic division from a prior mitosis, though there is not always an interphase between the first and second meiotic divisions. One might have suspected that cells were not just biding their time between mitoses, but it was only in the middle of the twentieth century that the cell cycle was fully characterized, showing interphase to be a long and very productive time in the life of a cell.
In an elegant experiment, cultured cells were exposed to radioactive thymidine, a DNA precursor. After a few minutes, radioactive DNA was detected in the nuclei of some cells. However, no cells actually in mitosis were radioactive. This meant that DNA is not synthesized during mitosis. Radioactive condensed mitotic chromosomes were detected only four to five hours after cells had been exposed to the radioactive DNA precursor, suggesting that replication had ended four to five hours before the beginning of mitosis. Studies like this eventually revealed the five major intervals of the cell cycle: mitosis, cytokinesis, gap 1 (the G1 phase, a time of cell growth), DNA synthesis (the S phase of DNA synthesis), and gap 2 (the G2 phase, during which a...
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Controlling the Cell Cycle (Genetics & Inherited Conditions)
Sometimes cells receive faulty instructions (for example, from environmental carcinogens) or respond inappropriately to otherwise normal commands from other cells. Cancer is a group of diseases in which normal regulation of the cell cycle has been lost and cells divide out of control. In research published in the 1970’s, cells synchronized in mitosis were mixed with others synchronized in other phases of the cell cycle in the presence of polyethylene glycol (the main ingredient in automobile antifreeze). The antifreeze caused cells to fuse. Right after mixing, chromosomes and a mitotic spindle could be seen alongside an intact nucleus in the fused cells. Later, the intact nucleus broke down and chromosomes condensed. The conclusion from studies like this is that mitosing cells contain a substance that causes nuclear breakdown and chromosome condensation in nonmitosing cells. Similar results were seen when cells in meiosis were fused with nonmeiotic cells. When purified, the substances from meiotic and mitotic cells could be injected into nonmitosing cells, where they caused nuclear breakdown and the appearance of chromosomes from chromatin. The substance was called maturation (or mitosis) promoting factor (MPF). MPF contains one polypetide called cyclin and another called cyclin-dependent kinase (cdk). The kinase enzyme catalyzes transfer of a phosphate to other proteins; it is active only when bound to cyclin—hence...
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Further Reading (Genetics & Inherited Conditions)
Alberts, Bruce, et al. Molecular Biology of the Cell. 5th ed. New York: Garland Science, 2008. This cell biology textbook contains numerous references to cell division.
Baringa, M. “A New Twist to the Cell Cycle.” Science 269, no. 5524 (August 4, 1995): 631-632. Addresses how periodic changes in cyclin concentrations regulate the cell cycle.
Campbell, Neil A., and Jane Reece. Biology. 8th ed. San Francisco: Pearson, Benjamin Cummings, 2008. Includes a detailed account of meiosis in a standard textbook for undergraduate majors.
Karp, Gerald. Cell and Molecular Biology: Concepts and Experiments. 5th ed. Chichester, England: John Wiley and Sons, 2008. Detailed accounts of mitosis and events and regulation of the cell by cyclins and kinases are included in this standard textbook for professionals and undergraduate majors.
Morgan, David O. The Cell Cycle: Principles of Control. London: New Science Press in association with Oxford University Press, 2007. Explains the mechanisms that control cell division, including a description of the phases and main events of the cell cycle, the main model organisms in cell-cycle analysis, cell-cycle control in development, and the failure of controls in cancer.
Murray, A. W., and Tim Hunt. The Cell Cycle: An Introduction. New York: W. H. Freeman, 1993. An informative overview for both students and general...
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Web Sites of Interest (Genetics & Inherited Conditions)
The American Society for Cell Biology, Image and Video Library. http://cellimages.ascb.org. The society’s library has a section with more than twenty images and videos that demonstrate the processes of cell division, growth, and death.
Cells Alive!. http://www.cellsalive.com. Cells Alive! provides interactive visuals that enable users to learn about the structure and function of eukaryotic cells. The site contains individual pages with text and animation that explain the cell cycle, animal cell meiosis, and animal cell mitosis.
Kimball’s Biology Pages. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages. John Kimball, a retired Harvard University biology professor, includes pages about the cell cycle, meiosis, and mitosis in his online cell biology text.
Nova Online, How Cells Divide: Mitosis Versus Meiosis. http://www.pbs.org/wgbh/nova/baby/divide.html. The process of cell division is explained in several formats, including one that uses flash animation technology.
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Cell Division (Encyclopedia of Nursing & Allied Health)
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 information as the original cell. Both processes are accompanied by cytokinesis, the division of the cytoplasm.
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 Down syndrome are due to an error in meiosis that results in an extra chromosome (extra chromosome 21) being present in the fertilized egg. This condition is called trisomy 21. The individual who develops from this egg will have the clinical features of Down syndrome including mental retardation. Trisomy 21, as well as other similar chromosome errors, occurs more often in the pregnancies of women as they get older. For example, older women have a higher risk for miscarriages associated with chromosome errors. They also have a higher risk of giving birth to an infant with trisomy 21 Down syndrome or a similar chromosome abnormality. For this reason, women in their mid-30s or older are usually referred to a geneticist or genetic counselor to learn about prenatal testing options such as amniocentesis and chorionic villus sampling (CVS).
Amniocentesis 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) 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.
Chromosomestructures in the nucleus of a cell that contain a thread of DNA containing the genetic information (genes). Humans have 46 chromosomes in 23 pairs.
Cytoplasmhe portion of the cell that surrounds the nucleus.
DNAeoxyribonucleic acid, the molecule that encodes the genes.
Genetic counselorn 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 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.
Nucleushe membrane-bound body within a cell that contains the chromosomes.
Carlson, Bruce M. Human Embryology and Developmental Biology. 2nd ed. St. Louis: Mosby, 1999.
Endow, Sharyn A., and David M. Glover, eds. Dynamics of Cell Division. New York: Oxford University Press, 1998.
Jorde, Lynn B., et al. Medical Genetics. 2nd ed. New York: Mosby, 1999.
Tortora, Gerard, and Sandra Reynolds Grabowski. Principles of Anatomy and Physiology. 9th ed. New York: HarperCollins, 2000.
The Biology Project. <<a href="http://www.biology.arizona.edu">http://www.biology.arizona.edu>.
Mitosis Animation. <<a href="http://galileo.physiology.uiowwa.edu/animations/mitosis.htm">http://galileo.physiology.uiowwa.edu/animations/mitosis.htm>.
Sallie Boineau Freeman, PhD