Meiosis

Not to be confused with Mitosis, Miosis, Myositis. Note that mitosis is the process by which most cells divide to produce two copies of themselves.

For the figure of speech, see Meiosis (figure of speech).

File:Meiosis Overview.svg

In meiosis, the chromosomes duplicate (during interphase) and homologous chromosomes exchange genetic information (chromosomal crossover) before a first division, called meiosis I. The daughter cells divide again in meiosis II, splitting up sister chromatids to form haploid gametes. Male and female gametes fuse during fertilization, creating a diploid cell with a complete set of paired chromosomes.

A video of meiosis I in a crane-fly spermatocyte, played back at 120× the recorded speed.

Meiosis ⁱ/maɪˈoʊsᵻs/ is a specialized type of cell division that reduces the chromosome number by half. This process occurs in all sexually reproducing single-celled and multicellular eukaryotes, including animals, plants, and fungi. Errors in meiosis resulting in aneuploidy are the leading known cause of miscarriage and the most frequent genetic cause of developmental disabilities.

In meiosis, DNA replication is followed by two rounds of cell division to produce four potential daughter cells, each with half the number of chromosomes as the original parent cell. The two meiotic divisions are known as Meiosis I and Meiosis II. Before meiosis begins, during S phase of the cell cycle, the DNA of each chromosome is replicated so that it consists of two identical sister chromatids, which remain held together through sister chromatid cohesion. This S-phase can be referred to as "premeiotic S-phase" or "meiotic S-phase." Immediately following DNA replication, meiotic cells enter a prolonged G2-like stage known as meiotic prophase. During this time, homologous chromosomes pair with each other and undergo genetic recombination, a programmed process in which DNA is cut and then repaired, which allows them to exchange some of their genetic information. A subset of recombination events results in crossovers, which create physical links known as chiasmata (singular:chiasma, for the Greek letter Chi) between the homologous chromosomes. In most organisms, these links are essential to direct each pair of homologous chromosomes to segregate away from each other during Meiosis I, resulting in two haploid cells that half the number of chromosomes as the parent cell. During Meiosis II, the cohesion between sister chromatids is released and they segregate from one another, as during mitosis. In some cases all four of the meiotic products form gametes such as sperm, spores, or pollen. In female animals, three of the four meiotic products are typically eliminated by extrusion into polar bodies, and only one cell develops to produce an ovum.

Because the number of chromosomes is halved during meiosis, gametes can fuse (i.e. fertilization) to form a diploid zygote that contains two copies of each chromosome, one from each parent. Thus, alternating cycles of meiosis and fertilization enable sexual reproduction, with successive generations maintaining the same number of chromosomes. For example, diploid human cells contain 23 pairs of chromosomes (46 total), half of maternal origin and half of paternal origin. Meiosis produces haploid gametes (ova or sperm) that contain one set of 23 chromosomes. When two gametes (an egg and a sperm) fuse, the resulting zygote is once again diploid, with the mother and father each contributing 23 chromosomes. This same pattern, but not the same number of chromosomes, occurs in all organisms that utilize meiosis.

Overview

While the process of meiosis is related to the more general cell division process of mitosis, it differs in two important respects:

recombination	meiosis	shuffles the genes between the two chromosomes in each pair (one received from each parent), producing recombinant chromosomes with unique genetic combinations in every gamete
	mitosis	occurs only if needed to repair DNA damage; usually occurs between identical sister chromatids and does not result in genetic changes
chromosome number (ploidy)	meiosis	produces four genetically unique cells, each with half the number of chromosomes as in the parent
	mitosis	produces two genetically identical cells, each with the same number of chromosomes as in the parent

Meiosis begins with a diploid cell, which contains two copies of each chromosome, termed homologs. First, the cell undergoes DNA replication, so each homolog now consists of two identical sister chromatids. Then each set of homologs pair with each other and exchange DNA by homologous recombination leading to physical connections (crossovers) between the homologs. In the first meiotic division, the homologs are segregated to separate daughter cells by the spindle apparatus. The cells then proceed to a second division without an intervening round of DNA replication. The sister chromatids are segregated to separate daughter cells to produce a total of four haploid cells. Female animals employ a slight variation on this pattern and produce one large ovum and two small polar bodies. Because of recombination, an individual chromatid can consist of a new combination of maternal and paternal DNA, resulting in offspring that are genetically distinct from either parent. Furthermore, an individual gamete can include an assortment of maternal, paternal, and recombinant chromatids. This genetic diversity resulting from sexual reproduction contributes to the variation in traits upon which natural selection can act.

Meiosis uses many of the same mechanisms as mitosis, the type of cell division used by eukaryotes to divide one cell into two identical daughter cells. In some plants, fungi, and protists meiosis results in the formation of spores: haploid cells that can divide vegetatively without undergoing fertilization. Some eukaryotes, like bdelloid rotifers, do not have the ability to carry out meiosis and have acquired the ability to reproduce by parthenogenesis.

Meiosis does not occur in archaea or bacteria, which generally reproduce via asexual processes such as binary fission. However, a "sexual" process known as horizontal gene transfer involves the transfer of DNA from one bacterium or archaeon to another and recombination of these DNA molecules of different parental origin.

History

Meiosis was discovered and described for the first time in sea urchin eggs in 1876 by the German biologist Oscar Hertwig. It was described again in 1883, at the level of chromosomes, by the Belgian zoologist Edouard Van Beneden, in Ascaris roundworm eggs. The significance of meiosis for reproduction and inheritance, however, was described only in 1890 by German biologist August Weismann, who noted that two cell divisions were necessary to transform one diploid cell into four haploid cells if the number of chromosomes had to be maintained. In 1911 the American geneticist Thomas Hunt Morgan detected crossovers in meiosis in the fruit fly Drosophila melanogaster, which helped to establish that genetic traits are transmitted on chromosomes.

The term meiosis (originally spelled "maiosis") was introduced to biology by J.B. Farmer and J.E.S. Moore in 1905:

We propose to apply the terms Maiosis or Maiotic phase to cover the whole series of nuclear changes included in the two divisions that were designated as Heterotype and Homotype by Flemming.

It is derived from the Greek word μείωσις, meaning 'lessening'.

Occurrence in eukaryotic life cycles

Gametic life cycle.

Zygotic life cycle.

Main article: Biological life cycle

Meiosis occurs in eukaryotic life cycles involving sexual reproduction, consisting of the constant cyclical process of meiosis and fertilization. This takes place alongside normal mitotic cell division. In multicellular organisms, there is an intermediary step between the diploid and haploid transition where the organism grows. At certain stages of the life cycle, germ cells produce gametes. Somatic cells make up the body of the organism and are not involved in gamete production.

Cycling meiosis and fertilization events produces a series of transitions back and forth between alternating haploid and diploid states. The organism phase of the life cycle can occur either during the diploid state (gametic or diploid life cycle), during the haploid state (zygotic or haploid life cycle), or both (sporic or haplodiploid life cycle, in which there are two distinct organism phases, one during the haploid state and the other during the diploid state). In this sense there are three types of life cycles that utilize sexual reproduction, differentiated by the location of the organism phase(s).

In the gametic life cycle or " diplontic life cycle", of which humans are a part, the organism is diploid, grown from a diploid cell called the zygote. The organism's diploid germ-line stem cells undergo meiosis to create haploid gametes (the spermatozoa for males and ova for females), which fertilize to form the zygote. The diploid zygote undergoes repeated cellular division by mitosis to grow into the organism.

In the zygotic life cycle the organism is haploid instead, spawned by the proliferation and differentiation of a single haploid cell called the gamete. Two organisms of opposing gender contribute their haploid gametes to form a diploid zygote. The zygote undergoes meiosis immediately, creating four haploid cells. These cells undergo mitosis to create the organism. Many fungi and many protozoa utilize the zygotic life cycle.

Finally, in the sporic life cycle, the living organism alternates between haploid and diploid states. Consequently, this cycle is also known as the alternation of generations. The diploid organism's germ-line cells undergo meiosis to produce spores. The spores proliferate by mitosis, growing into a haploid organism. The haploid organism's gamete then combines with another haploid organism's gamete, creating the zygote. The zygote undergoes repeated mitosis and differentiation to become a diploid organism again. The sporic life cycle can be considered a fusion of the gametic and zygotic life cycles.

Process

A diagram of the meiotic phases

The preparatory steps that lead up to meiosis are identical in pattern and name to interphase of the mitotic cell cycle.

Interphase is divided into three phases:

• Growth 1 (G₁) phase: In this very active phase, the cell synthesizes its vast array of proteins, including the enzymes and structural proteins it will need for growth. In G₁, each of the chromosomes consists of a single linear molecule of DNA.
• Synthesis (S) phase: The genetic material is replicated; each of the cell's chromosomes duplicates to become two identical sister chromatids attached at a centromere. This replication does not change the ploidy of the cell since the centromere number remains the same. The identical sister chromatids have not yet condensed into the densely packaged chromosomes visible with the light microscope. This will take place during prophase I in meiosis.
• Growth 2 (G₂) phase: G₂ phase as seen before mitosis is not present in meiosis. Meiotic prophase corresponds most closely to the G₂ phase of mitotic cell cycle.

Interphase is followed by meiosis I and then meiosis II. Meiosis I separates homologous chromosome, each still made up of two sister chromatids, into two daughter cells, thus reducing the chromosome number by half. During meiosis II, sister chromatids decouple and the resultant daughter chromosomes are segregated into four daughter cells. For diploid organisms, the daughter cells resulting from meiosis are haploid and contain only one copy of each chromosome. In some species, cells enter a resting phase known as interkinesis between meiosis I and meiosis II.

Meiosis I and II are each divided into prophase, metaphase, anaphase, and telophase stages, similar in purpose to their analogous subphases in the mitotic cell cycle. Therefore, meiosis includes the stages of meiosis I (prophase I, metaphase I, anaphase I, telophase I) and meiosis II (prophase II, metaphase II, anaphase II, telophase II).

Meiosis generates gamete genetic diversity in two ways: (1) the independent orientation of homologous chromosome pairs along the metaphase plate during metaphase I and the subsequent separation of homologs during anaphase I allows a random and independent distribution of chromosomes to each daughter cell (and ultimately to gametes); and (2) physical exchange of homologous chromosomal regions by homologous recombination during prophase I results in new combinations of DNA within chromosomes.

During meiosis, specific genes are more highly transcribed. In addition to strong meiotic stage-specific expression of mRNA, there are also pervasive translational controls (e.g. selective usage of preformed mRNA), regulating the ultimate meiotic stage-specific protein expression of genes during meiosis. Thus, both transcriptional and translational controls determine the broad restructuring of meiotic cells needed to carry out meiosis.

Phases

Meiosis is divided into meiosis I and meiosis II which are further divided into Karyokinesis I and Cytokinesis I & Karyokinesis II and Cytokinesis II respectively.

Meiosis I

Meiosis I segregates homologous chromosomes, producing two haploid cells (n chromosomes, 23 in humans). Because the ploidy is reduced from diploid to haploid, meiosis I is referred to as a reductional division. Meiosis II is an equational division analogous to mitosis, in which the sister chromatids are segregated, creating four haploid daughter cells .

Prophase I

Prophase I is typically the longest phase of meiosis. During prophase I, homologous chromosomes pair and exchange DNA in a process called homologous recombination. This often results in chromosomal crossover. This process is critical for pairing between homologous chromosomes and hence for accurate segregation of the chromosomes at the first meiosis division. The new combinations of DNA created during crossover are a significant source of genetic variation, and result in new combinations of alleles, which may be beneficial. The paired and replicated chromosomes are called bivalents or tetrads, which have two chromosomes and four chromatids, with one chromosome coming from each parent. The process of pairing the homologous chromosomes is called synapsis. At this stage, non-sister chromatids may cross-over at points called chiasmata (plural; singular chiasma). Prophase I has historically been divided into a series of substages which are named according to the appearance of chromosomes.

Leptotene

The first stage of prophase I is the leptotene stage, also known as leptonema, from Greek words meaning "thin threads".In this stage of prophase I, individual chromosomes—each consisting of two sister chromatids—become "individualized" to form visible strands within the nucleus. The two sister chromatids closely associated and are visually indistinguishable from one another. During leptotene, lateral elements of the synaptonemal complex assemble. Leptotene is of very short duration and progressive condensation and coiling of chromosome fibers takes place.

Zygotene

The zygotene stage, also known as zygonema, from Greek words meaning "paired threads", occurs as the chromosomes approximately line up with each other into homologous chromosome pairs. In some organisms, this is called the bouquet stage because of the way the telomeres cluster at one end of the nucleus. At this stage, the synapsis (pairing/coming together) of homologous chromosomes takes place, facilitated by assembly of central element of the synaptonemal complex. Pairing is brought about in a zipper-like fashion and may start at the centromere (procentric), at the chromosome ends (proterminal), or at any other portion (intermediate). Individuals of a pair are equal in length and in position of the centromere. Thus pairing is highly specific and exact. The paired chromosomes are called bivalent or tetrad chromosomes.

Pachytene

The pachytene (pronounced /ˈpækᵻtiːn/ PAK-ə-teen) stage, also known as pachynema, from Greek words meaning "thick threads",. At this point a tetrad of the chromosomes has formed known as a bivalent. This is the stage when chromosomal crossover (crossing over) occurs. Nonsister chromatids of homologous chromosomes may exchange segments over regions of homology. Sex chromosomes, however, are not wholly identical, and only exchange information over a small region of homology. At the sites where exchange happens, chiasmata form. The exchange of information between the non-sister chromatids results in a recombination of information; each chromosome has the complete set of information it had before, and there are no gaps formed as a result of the process. Because the chromosomes cannot be distinguished in the synaptonemal complex, the actual act of crossing over is not perceivable through the microscope, and chiasmata are not visible until the next stage.

Diplotene

During the diplotene stage, also known as diplonema, from Greek words meaning "two threads", the synaptonemal complex degrades and homologous chromosomes separate from one another a little. The chromosomes themselves uncoil a bit, allowing some transcription of DNA. However, the homologous chromosomes of each bivalent remain tightly bound at chiasmata, the regions where crossing-over occurred. The chiasmata remain on the chromosomes until they are severed at the transition to anaphase I.

In mammalian and human fetal oogenesis all developing oocytes develop to this stage and are arrested before birth. This suspended state is referred to as the dictyotene stage or dictyate. It lasts until meiosis is resumed to prepare the oocyte for ovulation, which happens at puberty or even later.

Diakinesis

Chromosomes condense further during the diakinesis stage, from Greek words meaning "moving through". This is the first point in meiosis where the four parts of the tetrads are actually visible. Sites of crossing over entangle together, effectively overlapping, making chiasmata clearly visible. Other than this observation, the rest of the stage closely resembles prometaphase of mitosis; the nucleoli disappear, the nuclear membrane disintegrates into vesicles, and the meiotic spindle begins to form.

Synchronous processes

During these stages, two centrosomes, containing a pair of centrioles in animal cells, migrate to the two poles of the cell. These centrosomes, which were duplicated during S-phase, function as microtubule organizing centers nucleating microtubules, which are essentially cellular ropes and poles. The microtubules invade the nuclear region after the nuclear envelope disintegrates, attaching to the chromosomes at the kinetochore. The kinetochore functions as a motor, pulling the chromosome along the attached microtubule toward the originating centrosome, like a train on a track. There are four kinetochores on each tetrad, but the pair of kinetochores on each sister chromatid fuses and functions as a unit during meiosis I.

Microtubules that attach to the kinetochores are known as kinetochore microtubules. Other microtubules will interact with microtubules from the opposite centrosome: these are called nonkinetochore microtubules or polar microtubules. A third type of microtubules, the aster microtubules, radiates from the centrosome into the cytoplasm or contacts components of the membrane skeleton.

Metaphase I

Homologous pairs move together along the metaphase plate: As kinetochore microtubules from both centrosomes attach to their respective kinetochores, the paired homologous chromosomes align along an equatorial plane that bisects the spindle, due to continuous counterbalancing forces exerted on the bivalents by the microtubules emanating from the two kinetochores of homologous chromosomes. The physical basis of the independent assortment of chromosomes is the random orientation of each bivalent along the metaphase plate, with respect to the orientation of the other bivalents along the same equatorial line. The protein complex cohesin holds sister chromatids together from the time of their replication until anaphase. In mitosis, the force of kinetochore microtubules pulling in opposite directions creates tension. The cell senses this tension and does not progress with anaphase until all the chromosomes are properly bi-oriented. In meiosis, establishing tension requires at least one crossover per chromosome pair in addition to cohesin between sister chromatids.

Anaphase I

Kinetochore microtubules shorten, pulling homologous chromosomes (which consist of a pair of sister chromatids) to opposite poles. Nonkinetochore microtubules lengthen, pushing the centrosomes farther apart. The cell elongates in preparation for division down the center. Unlike in mitosis, only the cohesin from the chromosome arms is degraded while the cohesin surrounding the centromere remains protected. This allows the sister chromatids to remain together while homologs are segregated.

Telophase I

The first meiotic division effectively ends when the chromosomes arrive at the poles. Each daughter cell now has half the number of chromosomes but each chromosome consists of a pair of chromatids. The microtubules that make up the spindle network disappear, and a new nuclear membrane surrounds each haploid set. The chromosomes uncoil back into chromatin. Cytokinesis, the pinching of the cell membrane in animal cells or the formation of the cell wall in plant cells, occurs, completing the creation of two daughter cells. Sister chromatids remain attached during telophase I.

Cells may enter a period of rest known as interkinesis or interphase II. No DNA replication occurs during this stage.

Meiosis II

Meiosis II is the second meiotic division, and usually involves equational segregation, or separation of sister chromatids. Mechanically, the process is similar to mitosis, though its genetic results are fundamentally different. The end result is production of four haploid cells (n chromosomes, 23 in humans) from the two haploid cells (with n chromosomes, each consisting of two sister chromatids) produced in meiosis I. The four main steps of Meiosis II are: Prophase II, Metaphase II, Anaphase II, and Telophase II.

In prophase II we see the disappearance of the nucleoli and the nuclear envelope again as well as the shortening and thickening of the chromatids. Centrosomes move to the polar regions and arrange spindle fibers for the second meiotic division.

In metaphase II, the centromeres contain two kinetochores that attach to spindle fibers from the centrosomes at opposite poles. The new equatorial metaphase plate is rotated by 90 degrees when compared to meiosis I, perpendicular to the previous plate.

This is followed by anaphase II, in which the remaining centromeric cohesin is cleaved allowing the sister chromatids to segregate. The sister chromatids by convention are now called sister chromosomes as they move toward opposing poles.

The process ends with telophase II, which is similar to telophase I, and is marked by decondensation and lengthening of the chromosomes and the disassembly of the spindle. Nuclear envelopes reform and cleavage or cell wall formation eventually produces a total of four daughter cells, each with a haploid set of chromosomes.

Meiosis is now complete and ends up with four new daughter cells.

Origin and function

Main article: Origin and function of meiosis

The origin and function of meiosis are fundamental to understanding the evolution of sexual reproduction in Eukaryotes. There is no current consensus among biologists on the questions of how sex in Eukaryotes arose in evolution, what basic function sexual reproduction serves, and why it is maintained, given the basic two-fold cost of sex. It is clear that it evolved over 1.2 billion years ago, and that almost all species which are descendents of the original sexually reproducing species are still sexual reproducers, including plants, fungi, and animals.

Meiosis is ubiquitous among eukaryotes. It occurs in single-celled organisms such as yeast, as well as in multicellular organisms, such as humans. Eukaryotes arose from prokaryotes more than 1.5 billion years ago, and the earliest eukaryotes were likely single-celled organisms. To understand sex in eukaryotes, it is necessary to understand (1) how meiosis arose in single celled eukaryotes, and (2) the function of meiosis.

Nondisjunction

Main article: Nondisjunction

The normal separation of chromosomes in meiosis I or sister chromatids in meiosis II is termed disjunction. When the segregation is not normal, it is called nondisjunction. This results in the production of gametes which have either too many or too few of a particular chromosome, and is a common mechanism for trisomy or monosomy. Nondisjunction can occur in the meiosis I or meiosis II, phases of cellular reproduction, or during mitosis.

Most monosomic and trisomic human embryos are not viable, but some aneuploidies can be tolerated, such as trisomy for the smallest chromosome, chromosome 21. Phenotypes of these aneuploidies range from severe developmental disorders to asymptomatic. Medical conditions include but are not limited to:

• Down Syndrome - trisomy of chromosome 21
• Patau Syndrome - trisomy of chromosome 13
• Edward Syndrome - trisomy of chromosome 18
• Klinefelter Syndrome - extra X chromosomes in males - i.e. XXY, XXXY, XXXXY, etc.
• Turner Syndrome - lacking of one X chromosome in females - i.e. X0
• Triple X syndrome - an extra X chromosome in females
• XYY Syndrome - an extra Y chromosome in males.

The probability of nondisjunction in human oocytes increases with increasing maternal age, presumably due to loss of cohesin over time.

Meiosis in plants and animals

Meiosis occurs in all animals and plants. The end result, the production of gametes with half the number of chromosomes as the parent cell, is the same, but the detailed process is different. In animals, meiosis produces gametes directly. In land plants and some algae, there is an alternation of generations such that meiosis in the diploid sporophyte generation produces haploid spores. These spores multiply by mitosis, developing into the haploid gametophyte generation, which then gives rise to gametes directly (i.e. without further meiosis). In both animals and plants, the final stage is for the gametes to fuse, restoring the original number of chromosomes.

Meiosis in mammals

In females, meiosis occurs in cells known as oocytes (singular: oocyte). Each oocyte that initiates meiosis divides twice, unequally in each case. The first division produces a daughter cell that will undergo a second division, and a much smaller "polar body" that is extruded from the surface of the cell and does not divide further. Following Meiosis II, a "second polar body" is extruded, and the single remaining haploid cell enlarges to become an ovum. Since the first polar body normally disintegrates rather than dividing again, meiosis in female mammals results in three products, the oocyte and two polar bodies. However, before these divisions occur, these cells stop at the diplotene stage of meiosis I and lie dormant within a protective shell of somatic cells called the follicle. Follicles begin growth at a steady pace in a process known as folliculogenesis, and a small number enter the menstrual cycle. Menstruated oocytes continue meiosis I and arrest at meiosis II until fertilization. The process of meiosis in females occurs during oogenesis, and differs from the typical meiosis in that it features a long period of meiotic arrest known as the dictyate stage and lacks the assistance of centrosomes.

In males, meiosis occurs during spermatogenesis in the seminiferous tubules of the testicles. Meiosis during spermatogenesis is specific to a type of cell called spermatocytes that will later mature to become spermatozoa.

In female mammals, meiosis begins immediately after primordial germ cells migrate to the ovary in the embryo, but in the males, meiosis begins later, at the time of puberty. It is retinoic acid, derived from the primitive kidney (mesonephros) that stimulates meiosis in ovarian oogonia. Tissues of the male testis suppress meiosis by degrading retinoic acid, a stimulator of meiosis. This is overcome at puberty when cells within seminiferous tubules called Sertoli cells start making their own retinoic acid. Sensitivity to retinoic acid is also adjusted by proteins called nanos and DAZL.

Meiosis vs. mitosis

In order to understand meiosis, a comparison to mitosis is helpful. The table below shows the differences between meiosis and mitosis.

	Meiosis	Mitosis
End result	Normally four cells, each with half the number of chromosomes as the parent	Two cells, having the same number of chromosomes as the parent
Function	Sexual reproduction, production of gametes (sex cells)	Cellular reproduction, growth, repair, asexual reproduction
Where does it happen?	Reproductive cells of almost all eukaryotes (animals, plants, fungi, and protists)	All proliferating cells in all eukaryotes
Steps	Prophase I, Metaphase I, Anaphase I, Telophase I, Prophase II, Metaphase II, Anaphase II, Telophase II	Prophase, Prometaphase, Metaphase, Anaphase, Telophase
Genetically same as parent?	No	Yes
Crossing over happens?	Yes, normally occurs between each pair of homologous chromosomes	Very rarely
Pairing of homologous chromosomes?	Yes	No
Cytokinesis	Occurs in Telophase I and Telophase II	Occurs in Telophase
Centromeres split	Does not occur in Anaphase I, but occurs in Anaphase II	Occurs in Anaphase

See also

• Coefficient of coincidence
• DNA repair
• Evolution of sexual reproduction
• Fertilization
• Genetic recombination
• Mitosis
• Oxidative stress
• Synizesis (biology)

External links

• Meiosis Flash Animation
• Animations from the U. of Arizona Biology Dept.
• Meiosis at Kimball's Biology Pages
• Khan Academy, video lecture
• CCO The Cell-Cycle Ontology
• Stages of Meiosis animation
• *"Abby Denburg seminar: Chromosome Dynamics During Meiosis"