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{{Short description|Cell division producing haploid gametes}}
{{About||the figure of speech|Meiosis (figure of speech)|the process whereby cell nuclei divide to produce two copies of themselves|Mitosis|excessive constriction of the pupils|Miosis|the parasitic infestation|Myiasis|muscle inflammation|Myositis}}
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[[File:Meiosis Overview new.svg|thumb|300x300px|In meiosis, the [[chromosome]]s duplicate (during [[interphase]]) and [[homologous chromosome]]s exchange genetic information ([[chromosomal crossover]]) during the first division, called [[meiosis I]]. The daughter cells divide again in [[meiosis II]], splitting up [[sister chromatid]]s to form haploid [[gamete]]s. Two gametes fuse during [[fertilization]], forming a diploid cell ([[zygote]]) with a complete set of paired chromosomes.]]
[[File:Calyculin-A-an-enhancer-of-myosin-speeds-up-anaphase-chromosome-movement-1475-9268-6-1-S1.ogv|thumb|A video of meiosis I in a [[Nephrotoma suturalis|crane fly]] [[spermatocyte]], played back at 120× the recorded speed.]]

'''Meiosis''' ({{IPAc-en|m|aɪ|ˈ|oʊ|s|ɪ|s|audio=en-us-meiosis.ogg}}; {{etymology|grc|''{{wikt-lang|grc|μείωσις}}'' ({{grc-transl|μείωσις}})|lessening}}, (since it is a reductional division)<ref>{{Cite web|date=2019-10-01|title=4.1: Meiosis|url=https://bio.libretexts.org/Courses/University_of_Arkansas_Little_Rock/BIOL3300_Genetics/04%3A_Inheritance/4.01%3A_Meiosis|access-date=2021-05-29|website=Biology LibreTexts|language=en}}</ref><ref>{{Cite web|title=Definition of Reduction division|url=https://www.medicinenet.com/reduction_division/definition.htm|access-date=2021-05-29|website=MedicineNet|language=en}}</ref> is a special type of [[cell division]] of [[germ cells]] in [[Sexual reproduction|sexually-reproducing]] organisms that produces the [[gametes]], the [[sperm]] or [[egg cells]]. It involves two rounds of division that ultimately result in four cells, each with only one copy of each [[chromosome]] ([[haploid]]). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is [[Chromosomal crossover|crossed over]], creating new combinations of code on each chromosome.<ref name="Freeman-2011">{{cite book| vauthors = Freeman S |title=Biological Science|date=2011|publisher=Pearson|location=Hoboken, NY|page=210|edition=6th}}</ref> Later on, during [[fertilisation]], the haploid cells produced by meiosis from a male and a female will fuse to create a [[zygote]], a cell with two copies of each chromosome again.

Errors in meiosis resulting in [[aneuploidy]] (an abnormal number of chromosomes) are the leading known cause of [[miscarriage]] and the most frequent genetic cause of [[developmental disabilities]].<ref>{{cite journal | vauthors = Hassold T, Hunt P | title = To err (meiotically) is human: the genesis of human aneuploidy | journal = Nature Reviews Genetics | volume = 2 | issue = 4 | pages = 280–91 | date = April 2001 | pmid = 11283700 | doi = 10.1038/35066065 | s2cid = 22264575 }}</ref>

In meiosis, [[DNA replication]] is followed by two rounds of cell division to produce four daughter cells, each with half the number of [[chromosome]]s as the original parent cell.<ref name="Freeman-2011" /> 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 phase|G<sub>2</sub>]]-like stage known as meiotic [[prophase]]. During this time, [[homologous chromosome]]s pair with each other and undergo [[genetic recombination]], a programmed process in which DNA may be cut and then repaired, which allows them to exchange some of their [[genetic information]]. A subset of recombination events results in [[chromosomal crossover|crossovers]], which create physical links known as [[Chiasma (genetics)|chiasmata]] (singular: chiasma, for the Greek letter [[Chi (letter)|Chi]], Χ) between the homologous chromosomes. In most organisms, these links can help direct each pair of homologous chromosomes to [[chromosome segregation|segregate]] away from each other during meiosis I, resulting in two [[haploid]] cells that have 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 including 1 pair of sex 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.

Meiosis occurs in all sexually-reproducing single-celled and [[Multicellular organism|multicellular]] organisms (which are all [[eukaryote]]s), including [[animal]]s, [[plant]]s and [[fungi]].<ref name="Letunic I and Bork P">{{cite web|url=http://itol.embl.de/|title=Interactive Tree of Life|year=2006|url-status=live|archive-url=https://web.archive.org/web/20180129083127/http://itol.embl.de/|archive-date=29 January 2018|access-date=23 July 2011|vauthors=Letunic I, Bork P}}</ref><ref name="Bernstein2010">{{cite journal|vauthors=Bernstein H, Bernstein C|year=2010|title=Evolutionary origin of recombination during meiosis|journal=BioScience|volume=60|issue=7|pages=498–505|doi=10.1525/bio.2010.60.7.5|s2cid=86663600}}</ref><ref>{{cite journal|vauthors=Lodé T|date=June 2011|title=Sex is not a solution for reproduction: the libertine bubble theory|journal=BioEssays|volume=33|issue=6|pages=419–22|doi=10.1002/bies.201000125|pmid=21472739|doi-access=free}}</ref> It is an essential process for [[oogenesis]] and [[spermatogenesis]].

==Overview==
Although the process of meiosis is related to the more general cell division process of [[mitosis]], it differs in two important respects:
{| class="wikitable" style="margin: 1em auto 1em auto"
|+align=bottom style="text-align:left;"|
|-
! rowspan=2 style="background: #DDEEFF;" | recombination
| meiosis
| align="center" |  [[Genetic recombination|shuffles the genes]] between the two chromosomes in each pair (one received from each parent), producing lots of recombinant chromosomes with unique genetic combinations in every gamete
|-
| mitosis
| align="center" | occurs only if needed to repair DNA damage;
usually occurs between identical sister chromatids and does not result in genetic changes
|- bgcolor=#ccccff
! colspan=3  style="background:#dddddd;" |  &nbsp;
|-
! rowspan=2 style="background: #DDEEFF;" | chromosome number (ploidy)
| meiosis
| align="center" | produces four genetically unique cells, each with [[haploid|half]] the number of chromosomes as in the parent
|-
| mitosis
| align="center" |produces two genetically identical cells, each with [[Ploidy#Diploid|the same number]] of chromosomes as in the parent
|-
|colspan=12 style="background: #FFFFFF; border-right:1px solid white; border-bottom:1px solid white; border-left:1px solid white;"|
|}

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 genetic information by [[homologous recombination]] often leading to physical connections ([[Chromosomal crossover|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 three small polar bodies. Because of recombination, an individual chromatid can consist of a new combination of maternal and paternal genetic information, 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 [[eukaryote]]s to divide one cell into two identical daughter cells. In some plants, fungi, and [[protist]]s meiosis results in the formation of [[spore]]s: 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 asexually via [[binary fission]].  However, a "sexual" process known as [[horizontal gene transfer]] involves the transfer of DNA from one bacterium or [[archaea|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]] [[egg (biology)|egg]]s in 1876 by the German biologist [[Oscar Hertwig]]. It was described again in 1883, at the level of [[chromosome]]s, 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 [[United States|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" is derived from the Greek word {{lang|grc|μείωσις}}, meaning 'lessening'. It was introduced to biology by [[John Bretland Farmer|J.B. Farmer]] and [[John Edmund Sharrock Moore|J.E.S. Moore]] in 1905, using the idiosyncratic rendering "maiosis":
<blockquote>''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 [[Walther Flemming|Flemming]]''.<ref>{{cite journal |first1=J.B. |last1=Farmer |first2=J.E.S. |last2=Moore |title=On the Maiotic Phase (Reduction Divisions) in Animals and Plants |journal=Quarterly Journal of Microscopical Science |volume=48 |issue=192 |pages=489–558 |date=February 1904 |url=https://www.biodiversitylibrary.org/item/49110#page/511/mode/1up}} as quoted in the [[Oxford English Dictionary]], Third Edition, June 2001, [http://www.oed.com/view/Entry/115952 ''s.v.'']</ref></blockquote>

The spelling was changed to "meiosis" by Koernicke (1905) and by Pantel and De Sinety (1906) to follow the usual conventions for [[Romanization of Greek|transliterating Greek]].<ref>{{cite journal |vauthors=Battaglia E |title=Meiosis and mitosis: a terminological criticism |journal=Annali di Botanica |volume=43 |pages=101–140 |date=1985 |issn= |url=https://books.google.com/books?id=gantAAAAMAAJ}}</ref>

==Phases==

Meiosis is divided into [[meiosis I]] and [[meiosis II]] which are further divided into Karyokinesis I, Cytokinesis I, Karyokinesis II, and Cytokinesis II, respectively. The preparatory steps that lead up to meiosis are identical in pattern and name to interphase of the mitotic cell cycle.<ref>{{Cite web | vauthors = Carter JS | publisher = University of Cincinnati |url=http://biology.clc.uc.edu/courses/bio104/mitosis.htm|title=Mitosis|date=2012-10-27|archive-url=https://web.archive.org/web/20121027084115/http://biology.clc.uc.edu/courses/bio104/mitosis.htm|access-date=2018-02-09|archive-date=2012-10-27}}</ref> [[Interphase]] is divided into three phases:
* [[G1 phase|Growth 1 (G<sub>1</sub>) 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 G<sub>1</sub>, each of the chromosomes consists of a single linear molecule of DNA.
* [[S phase|Synthesis (S) phase]]: The genetic material is replicated; each of the cell's chromosomes duplicates to become two identical [[sister chromatid]]s 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.
* [[G2 phase|Growth 2 (G<sub>2</sub>) phase]]: G<sub>2</sub> phase as seen before mitosis is not present in meiosis. Meiotic prophase corresponds most closely to the G<sub>2</sub> phase of the mitotic cell cycle.

Interphase is followed by meiosis I and then meiosis II. Meiosis I separates replicated homologous chromosomes, 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).

{{wide image|Meiosis Stages.svg|1100px|Diagram of the meiotic phases}}

During meiosis, specific genes are more highly [[Transcription (genetics)|transcribed]].<ref>{{cite journal | vauthors = Zhou A, Pawlowski WP | title = Regulation of meiotic gene expression in plants | journal = Frontiers in Plant Science | volume = 5 | pages = 413 | date = August 2014 | pmid = 25202317 | pmc = 4142721 | doi = 10.3389/fpls.2014.00413 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Jung M, Wells D, Rusch J, Ahmad S, Marchini J, Myers SR, Conrad DF | title = Unified single-cell analysis of testis gene regulation and pathology in five mouse strains | journal = eLife | volume = 8 | pages = e43966 | date = June 2019 | pmid = 31237565 | pmc = 6615865 | doi = 10.7554/eLife.43966 | doi-access = free }}</ref> 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.<ref name="Brar_2012">{{cite journal | vauthors = Brar GA, Yassour M, Friedman N, Regev A, Ingolia NT, Weissman JS | title = High-resolution view of the yeast meiotic program revealed by ribosome profiling | journal = Science | volume = 335 | issue = 6068 | pages = 552–7 | date = February 2012 | pmid = 22194413 | pmc = 3414261 | doi = 10.1126/science.1215110 | bibcode = 2012Sci...335..552B }}</ref>  Thus, both transcriptional and translational controls determine the broad restructuring of meiotic cells needed to carry out meiosis.

===Meiosis I===
Meiosis I segregates [[homologous chromosome]]s, which are joined as tetrads (2n, 4c), producing two haploid cells (n chromosomes, 23 in humans) which each contain chromatid pairs (1n, 2c). 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 (1n, 1c).<ref>{{Harvnb|Freeman|2005|pp=244–45}}</ref>
[[File:Meiosis Prophase I.png|thumb|350px|Meiosis Prophase I in mice. In Leptotene (L), the axial elements (stained by SYCP3) begin to form. In Zygotene (Z), the transverse elements (SYCP1) and central elements of the synaptonemal complex are partially installed (appearing as yellow as they overlap with SYCP3). In Pachytene (P), it is fully installed except on the sex chromosomes. In Diplotene (D), it disassembles revealing chiasmata. CREST marks the centromeres.]]
[[File:Synaptonemal Complex.svg|thumb|350px|Schematic of the synaptonemal complex at different stages of prophase I and the chromosomes arranged as a linear array of loops.]]

====Prophase I====
Prophase I is by far the longest phase of meiosis (lasting 13 out of 14 days in mice<ref>{{cite journal | vauthors = Cohen PE, Pollack SE, Pollard JW | title = Genetic analysis of chromosome pairing, recombination, and cell cycle control during first meiotic prophase in mammals | journal = Endocrine Reviews | volume = 27 | issue = 4 | pages = 398–426 | date = June 2006 | pmid = 16543383 | doi = 10.1210/er.2005-0017 | doi-access = free }}</ref>). During prophase I, homologous maternal and paternal chromosomes pair, [[Synapsis|synapse]], and exchange genetic information (by [[homologous recombination]]), forming at least one crossover per chromosome.<ref>{{cite journal | vauthors = Hunter N | title = Meiotic Recombination: The Essence of Heredity | journal = Cold Spring Harbor Perspectives in Biology | volume = 7 | issue = 12 | pages = a016618 | date = October 2015 | pmid = 26511629 | pmc = 4665078 | doi = 10.1101/cshperspect.a016618 }}</ref> These crossovers become visible as chiasmata (plural; singular [[chiasma (genetics)|chiasma]]).<ref name="Freeman249-502">{{Harvnb|Freeman|2005|pp=249–250}}</ref> This process facilitates stable pairing between homologous chromosomes and hence enables accurate segregation of the chromosomes at the first meiotic division. The paired and replicated chromosomes are called bivalents (two chromosomes) or tetrads (four [[chromatids]]), with one chromosome coming from each parent. Prophase I is divided into a series of substages which are named according to the appearance of chromosomes.

===== Leptotene =====
{{Main|Leptotene stage}}

The first stage of prophase I is the ''leptotene'' stage, also known as ''leptonema'', from Greek words meaning "thin threads".<ref name="Snustad_2008">{{cite book | title=Principles of Genetics | vauthors = Snustad DP, Simmons MJ |date=December 2008 | edition=5th | isbn=978-0-470-38825-9 | publisher=Wiley}}</ref>{{rp|27}} In this stage of prophase I, individual chromosomes—each consisting of two replicated sister chromatids—become "individualized" to form visible strands within the nucleus.<ref name="Snustad_2008"/>{{rp|27}}<ref name="Lewins_Genes_X">{{cite book | title=Lewin's Genes X | edition=10th | vauthors=Krebs JE, Goldstein ES, Kilpatrick ST | isbn=978-0-7637-6632-0 | publisher=Jones & Barlett Learning | date=November 2009 | url-access=registration | url=https://archive.org/details/lewinsgenesx0000unse }}</ref>{{rp|353}} The chromosomes each form a linear array of loops mediated by [[cohesin]], and the lateral elements of the [[synaptonemal complex]] assemble forming an "axial element" from which the loops emanate.<ref name="Zickler-2015">{{cite journal | vauthors = Zickler D, Kleckner N | title = Recombination, Pairing, and Synapsis of Homologs during Meiosis | journal = Cold Spring Harbor Perspectives in Biology | volume = 7 | issue = 6 | pages = a016626 | date = May 2015 | pmid = 25986558 | pmc = 4448610 | doi = 10.1101/cshperspect.a016626 }}</ref> Recombination is initiated in this stage by the enzyme [[Spo11|SPO11]] which creates programmed [[Double-strand breaks|double strand breaks]] (around 300 per meiosis in mice).<ref>{{cite journal | vauthors = Baudat F, de Massy B | title = Regulating double-stranded DNA break repair towards crossover or non-crossover during mammalian meiosis | journal = Chromosome Research | volume = 15 | issue = 5 | pages = 565–77 | date = July 2007 | pmid = 17674146 | doi = 10.1007/s10577-007-1140-3 | s2cid = 26696085 | doi-access = free }}</ref> This process generates single stranded DNA filaments coated by [[RAD51]] and [[DMC1 (gene)|DMC1]] which invade the homologous chromosomes, forming inter-axis bridges, and resulting in the pairing/co-alignment of homologues (to a distance of ~400&nbsp;nm in mice).<ref name="Zickler-2015" /><ref>{{cite journal | vauthors = O'Connor C | title = Meiosis, genetic recombination, and sexual reproduction | journal = Nature Education | date = 2008 | volume = 1 | issue = 1 | pages = 174 | url = https://www.nature.com/scitable/topicpage/meiosis-genetic-recombination-and-sexual-reproduction-210/ }}</ref>

=====Zygotene=====
{{Main|Zygotene}}

Leptotene is followed by the ''zygotene'' stage, also known as ''zygonema'', from Greek words meaning "paired threads",<ref name="Snustad_2008"/>{{rp|27}} which in some organisms is also called the bouquet stage because of the way the telomeres cluster at one end of the nucleus.<ref>{{cite journal | vauthors = Link J, Jantsch V | title = Meiotic chromosomes in motion: a perspective from Mus musculus and Caenorhabditis elegans | journal = Chromosoma | volume = 128 | issue = 3 | pages = 317–330 | date = September 2019 | pmid = 30877366 | pmc = 6823321 | doi = 10.1007/s00412-019-00698-5 }}</ref> In this stage the homologous chromosomes become much more closely (~100&nbsp;nm) and stably paired (a process called synapsis) mediated by the installation of the transverse and central elements of the [[synaptonemal complex]].<ref name="Zickler-2015" /> Synapsis is thought to occur in a zipper-like fashion starting from a recombination nodule. The paired chromosomes are called bivalent or tetrad chromosomes.

=====Pachytene=====
{{Main|Pachytene}}
The ''pachytene'' stage ({{IPAc-en|ˈ|p|æ|k|ɪ|t|iː|n}} {{Respell|PAK|i|teen}}), also known as ''pachynema'', from Greek words meaning "thick threads".<ref name="Snustad_2008" />{{rp|27}} is the stage at which all autosomal chromosomes have synapsed. In this stage homologous recombination, including chromosomal crossover (crossing over), is completed through the repair of the double strand breaks formed in leptotene.<ref name="Zickler-2015" /> Most breaks are repaired without forming crossovers resulting in [[gene conversion]].<ref>{{cite journal | vauthors = Chen JM, Cooper DN, Chuzhanova N, Férec C, Patrinos GP | title = Gene conversion: mechanisms, evolution and human disease | journal = Nature Reviews. Genetics | volume = 8 | issue = 10 | pages = 762–75 | date = October 2007 | pmid = 17846636 | doi = 10.1038/nrg2193 | s2cid = 205484180 }}</ref> However, a subset of breaks (at least one per chromosome) form crossovers between non-sister (homologous) chromosomes resulting in the exchange of genetic information.<ref>{{cite journal | vauthors = Bolcun-Filas E, Handel MA | title = Meiosis: the chromosomal foundation of reproduction | journal = Biology of Reproduction | volume = 99 | issue = 1 | pages = 112–126 | date = July 2018 | pmid = 29385397 | doi = 10.1093/biolre/ioy021 | s2cid = 38589675 | doi-access = free }}</ref>  The exchange of information between the homologous 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 an ordinary light 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",<ref name="Snustad_2008"/>{{rp|30}} the [[synaptonemal complex]] disassembles and homologous chromosomes separate from one another a little. 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 to allow homologous chromosomes to move to opposite poles of the cell.

In human fetal [[oogenesis]], all developing oocytes develop to this stage and are arrested in prophase I before birth.<ref>{{Cite book|title=Thompson & Thompson genetics in medicine | vauthors = Nussbaum RL, McInnes RR, Willard HF, Hamosh A |isbn=978-1437706963|edition=8th|publisher=Elsevier |pages=19|oclc=908336124|date = 2015-05-21}}</ref> This suspended state is referred to as the [[dictyotene|''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".<ref name="Snustad_2008"/>{{rp|30}} 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 [[Nucleolus|nucleoli]] disappear, the [[nuclear membrane]] disintegrates into vesicles, and the [[Spindle apparatus|meiotic spindle]] begins to form.

=====Meiotic spindle formation=====
Unlike mitotic cells, human and mouse oocytes do not have [[centrosome]]s to produce the meiotic spindle. In mice, approximately 80 MicroTubule Organizing Centers (MTOCs) form a sphere in the ooplasm and begin to nucleate microtubules that reach out towards chromosomes, attaching to the chromosomes at the [[kinetochore]]. Over time, the MTOCs merge until two poles have formed, generating a barrel shaped spindle.<ref>{{cite journal | vauthors = Schuh M, Ellenberg J | title = Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes | journal = Cell | volume = 130 | issue = 3 | pages = 484–98 | date = August 2007 | pmid = 17693257 | doi = 10.1016/j.cell.2007.06.025 | s2cid = 5219323 | doi-access = free }}</ref> In human oocytes spindle microtubule nucleation begins on the chromosomes, forming an aster that eventually expands to surround the chromosomes.<ref>{{cite journal | vauthors = Holubcová Z, Blayney M, Elder K, Schuh M | title = Human oocytes. Error-prone chromosome-mediated spindle assembly favors chromosome segregation defects in human oocytes | journal = Science | volume = 348 | issue = 6239 | pages = 1143–7 | date = June 2015 | pmid = 26045437 | pmc = 4477045 | doi = 10.1126/science.aaa9529 | bibcode = 2015Sci...348.1143H }}</ref> Chromosomes then slide along the microtubules towards the equator of the spindle, at which point the chromosome kinetochores form end-on attachments to microtubules.<ref>{{cite journal | vauthors = Kitajima TS, Ohsugi M, Ellenberg J | title = Complete kinetochore tracking reveals error-prone homologous chromosome biorientation in mammalian oocytes | journal = Cell | volume = 146 | issue = 4 | pages = 568–81 | date = August 2011 | pmid = 21854982 | doi = 10.1016/j.cell.2011.07.031 | s2cid = 5637615 | doi-access = free }}</ref>

====Metaphase I====
Homologous pairs move together along the metaphase plate: As ''kinetochore microtubules'' from both spindle poles 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. This attachment is referred to as a bipolar attachment. The physical basis of the [[independent assortment]] of chromosomes is the random orientation of each bivalent along with the metaphase plate, with respect to the orientation of the other bivalents along the same equatorial line.<ref name="Freeman249-502"/> 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 ordinarily requires at least one crossover per chromosome pair in addition to cohesin between sister chromatids (see [[Chromosome segregation]]).

====Anaphase I====
Kinetochore microtubules shorten, pulling homologous chromosomes (which each 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.<ref name="Freeman249-502"/> Unlike in mitosis, only the cohesin from the chromosome arms is degraded while the cohesin surrounding the centromere remains protected by a protein named Shugoshin (Japanese for "guardian spirit"), what prevents the sister chromatids from separating.<ref name="Pierce, Benjamin 2009">Pierce, Benjamin (2009). «Chromosomes and Cell Reproduction». Genetics: A Conceptual Approach, Third Edition. W.H. FREEMAN AND CO. {{ISBN|9780716779285}} P. 32</ref> 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. 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. However, cytokinesis does not fully complete resulting in "cytoplasmic bridges" which enable the cytoplasm to be shared between daughter cells until the end of meiosis II.<ref>{{cite journal | vauthors = Haglund K, Nezis IP, Stenmark H | title = Structure and functions of stable intercellular bridges formed by incomplete cytokinesis during development | journal = Communicative & Integrative Biology | volume = 4 | issue = 1 | pages = 1–9 | date = January 2011 | pmid = 21509167 | pmc = 3073259 | doi = 10.4161/cib.13550 }}</ref> 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 result is the production of four haploid cells (n chromosomes; 23 in humans) from the two haploid cells (with n chromosomes, each consisting of two sister chromatids){{clarify|date=February 2023}} 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 [[kinetochore]]s 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.<ref>{{cite web |url=http://www.phschool.com/science/biology_place/biocoach/meiosis/metaii.html |publisher=Pearson |work=The Biology Place |title=BioCoach Activity: Concept 11: Meiosis II: Metaphase II |access-date=2018-02-10 |archive-url=https://web.archive.org/web/20180228110158/http://www.phschool.com/science/biology_place/biocoach/meiosis/metaii.html |archive-date=2018-02-28 |url-status=live }}</ref>

This is followed by '''anaphase II''', in which the remaining centromeric cohesin, not protected by Shugoshin anymore, is cleaved, allowing the sister chromatids to segregate. The sister chromatids by convention are now called sister chromosomes as they move toward opposing poles.<ref name="Pierce, Benjamin 2009"/>

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 re-form and cleavage or cell plate 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==

===Origin of meiosis===

Meiosis appears to be a fundamental characteristic of [[eukaryote|eukaryotic organisms]] and to have been present early in eukaryotic evolution.  Eukaryotes that were once thought to lack meiotic sex have recently been shown to likely have, or once have had, this capability.  As one example, [[Giardia duodenalis|''Giardia intestinalis'']], a common intestinal parasite, was previously considered to have descended from a lineage that predated the emergence of meiosis and sex. However, ''G. intestinalis'' has now been found to possess a core set of meiotic genes, including five meiosis specific genes.<ref>{{cite journal |vauthors=Ramesh MA, Malik SB, Logsdon JM |title=A phylogenomic inventory of meiotic genes; evidence for sex in Giardia and an early eukaryotic origin of meiosis |journal=Curr Biol |volume=15 |issue=2 |pages=185–91 |date=January 2005 |pmid=15668177 |doi=10.1016/j.cub.2005.01.003 |bibcode=2005CBio...15..185R |doi-access=free }}</ref>  Also evidence for [[genetic recombination|meiotic recombination]], indicative of [[sexual reproduction]], was found in ''G. intestinalis''.<ref>{{cite journal |vauthors=Cooper MA, Adam RD, Worobey M, Sterling CR |title=Population genetics provides evidence for recombination in Giardia |journal=Curr Biol |volume=17 |issue=22 |pages=1984–8 |date=November 2007 |pmid=17980591 |doi=10.1016/j.cub.2007.10.020 |bibcode=2007CBio...17.1984C |doi-access=free }}</ref>  Another example of organisms previously thought to be asexual are parasitic protozoa of the genus ''[[Leishmania]]'', which cause human disease.  However, these organisms were shown to have a sexual cycle consistent with a meiotic process.<ref>{{cite journal |vauthors=Akopyants NS, Kimblin N, Secundino N, Patrick R, Peters N, Lawyer P, Dobson DE, Beverley SM, Sacks DL |title=Demonstration of genetic exchange during cyclical development of Leishmania in the sand fly vector |journal=Science |volume=324 |issue=5924 |pages=265–8 |date=April 2009 |pmid=19359589 |pmc=2729066 |doi=10.1126/science.1169464 |bibcode=2009Sci...324..265A }}</ref>  Although [[amoeba]] were once generally regarded as asexual, evidence has been presented that most lineages are anciently sexual and that the majority of asexual groups probably arose recently and independently.<ref>{{cite journal |vauthors=Lahr DJ, Parfrey LW, Mitchell EA, Katz LA, Lara E |title=The chastity of amoebae: re-evaluating evidence for sex in amoeboid organisms |journal=Proc Biol Sci |volume=278 |issue=1715 |pages=2081–90 |date=July 2011 |pmid=21429931 |pmc=3107637 |doi=10.1098/rspb.2011.0289 }}</ref> Dacks and Rogers<ref>{{cite journal |vauthors=Dacks J, Roger AJ |title=The first sexual lineage and the relevance of facultative sex |journal=J Mol Evol |volume=48 |issue=6 |pages=779–83 |date=June 1999 |pmid=10229582 |doi=10.1007/pl00013156 |bibcode=1999JMolE..48..779D }}</ref> proposed, based on a phylogenetic analysis, that facultative sex was likely present in the common ancestor of eukaryotes.

===Genetic variation===

The new combinations of DNA created during meiosis are a significant source of [[genetic variation]] alongside mutation, resulting in new combinations of [[alleles]], which may be beneficial. Meiosis generates gamete genetic diversity in two ways: (1) [[Law of Independent Assortment]]. The independent orientation of homologous chromosome pairs along the metaphase plate during metaphase I and orientation of sister chromatids in metaphase II, this is the subsequent separation of homologs and sister chromatids during anaphase I and II, it allows a random and independent distribution of chromosomes to each daughter cell (and ultimately to gametes);<ref>{{cite journal | vauthors = Monaghan F, Corcos A | title = On the origins of the Mendelian laws | journal = The Journal of Heredity | volume = 75 | issue = 1 | pages = 67–9 | date = 1984-01-01 | pmid = 6368675 | doi = 10.1093/oxfordjournals.jhered.a109868 }}</ref> and (2) [[Crossing over, genetic|Crossing Over]]. The physical exchange of homologous chromosomal regions by homologous [[Homologous recombination|recombination]] during prophase I results in new combinations of genetic information within chromosomes.<ref>{{cite journal | vauthors = Saleem M, Lamb BC, Nevo E | title = Inherited differences in crossing over and gene conversion frequencies between wild strains of Sordaria fimicola from "Evolution Canyon" | journal = Genetics | volume = 159 | issue = 4 | pages = 1573–93 | date = December 2001 | pmid = 11779798 | pmc = 1461899 | doi = 10.1093/genetics/159.4.1573 }}</ref>  However, such physical exchange does not always occur during meiosis.  In the oocytes of the silkworm ''[[Bombyx mori]]'', meiosis is completely [[chiasma (genetics)|achiasmate]] (lacking crossovers).<ref>{{cite journal |vauthors=Xiang Y, Tsuchiya D, Guo F, Gardner J, McCroskey S, Price A, Tromer EC, Walters JR, Lake CM, Hawley RS |title=A molecular cell biology toolkit for the study of meiosis in the silkworm Bombyx mori |journal=G3 (Bethesda) |volume=13 |issue=5 |pages= |date=May 2023 |pmid=36911915 |pmc=10151401 |doi=10.1093/g3journal/jkad058 |url=}}</ref> Although [[synaptonemal complex]]es are present during the [[pachytene]] stage of meiosis in ''B. mori'', crossing-over [[homologous recombination]] is absent between the paired [[chromosome]]s.<ref>{{cite journal |vauthors=Rasmussen SW |title=The transformation of the Synaptonemal Complex into the 'elimination chromatin' in Bombyx mori oocytes |journal=Chromosoma |volume=60 |issue=3 |pages=205–21 |date=April 1977 |pmid=870294 |doi=10.1007/BF00329771 |url=}}</ref>

===Prophase I arrest===
Female mammals and birds are born possessing all the oocytes needed for future ovulations, and these [[oocyte]]s are arrested at the prophase I stage of meiosis.<ref name = Mira1998>{{cite journal | vauthors = Mira A | title = Why is meiosis arrested? | journal = Journal of Theoretical Biology | volume = 194 | issue = 2 | pages = 275–87 | date = September 1998 | pmid = 9778439 | doi = 10.1006/jtbi.1998.0761 | bibcode = 1998JThBi.194..275M }}</ref>  In humans, as an example, oocytes are formed between three and four months of [[gestation]] within the fetus and are therefore present at birth.  During this prophase I arrested stage ([[dictyate]]), which may last for decades, four copies of the [[genome]] are present in the oocytes. The arrest of ooctyes at the four genome copy stage was proposed to provide the informational redundancy needed to [[DNA repair|repair damage in the DNA]] of the [[germline]].<ref name = Mira1998/>  The repair process used appears to involve [[homologous recombination]]al repair<ref name = Mira1998/><ref name = Stringer2020>{{cite journal | vauthors = Stringer JM, Winship A, Zerafa N, Wakefield M, Hutt K | title = Oocytes can efficiently repair DNA double-strand breaks to restore genetic integrity and protect offspring health | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 117 | issue = 21 | pages = 11513–11522 | date = May 2020 | pmid = 32381741 | pmc = 7260990 | doi = 10.1073/pnas.2001124117 | bibcode = 2020PNAS..11711513S | doi-access = free }}</ref> Prophase I arrested oocytes have a high capability for efficient repair of [[DNA damage (naturally occurring)|DNA damage]], particularly exogenously induced double-strand breaks.<ref name = Stringer2020/>  DNA repair capability appears to be a key quality control mechanism in the female germ line and a critical determinant of [[fertility]].<ref name = Stringer2020/>

===Meiosis as an adaptation for repairing germline DNA===

[[Genetic recombination]] can be viewed as fundamentally a [[DNA repair]] process, and that when it occurs during meiosis it is an adaptation for repairing the [[genome|genomic]] [[DNA]] that is passed on to progeny.<ref>{{cite journal |vauthors=Bernstein H, Byerly HC, Hopf FA, Michod RE |title=Genetic damage, mutation, and the evolution of sex |journal=Science |volume=229 |issue=4719 |pages=1277–81 |date=September 1985 |pmid=3898363 |doi=10.1126/science.3898363 |bibcode=1985Sci...229.1277B }}</ref><ref>{{cite book |vauthors=Bernstein H, Hopf FA, Michod RE |chapter=The Molecular Basis of the Evolution of Sex |title=Molecular Genetics of Development |series=Advances in Genetics |volume=24 |pages=323–70 |date=1987 |pmid=3324702 |doi=10.1016/s0065-2660(08)60012-7 |isbn=978-0-12-017624-3 }}</ref>  Experimental findings indicate that a substantial benefit of meiosis is [[homologous recombination|recombinational repair]] of [[DNA damage (naturally occurring)|DNA damage]] in the [[germline]], as indicated by the following examples.  [[Hydrogen peroxide]] is an agent that causes [[oxidative stress]] leading to oxidative DNA damage.<ref>{{cite journal |vauthors=Slupphaug G, Kavli B, Krokan HE |title=The interacting pathways for prevention and repair of oxidative DNA damage |journal=Mutat Res |volume=531 |issue=1–2 |pages=231–51 |date=October 2003 |pmid=14637258 |doi=10.1016/j.mrfmmm.2003.06.002 |bibcode=2003MRFMM.531..231S }}</ref>  Treatment of the yeast ''[[Schizosaccharomyces pombe]]'' with [[hydrogen peroxide]] increased the frequency of mating and the formation of meiotic spores by 4 to 18-fold.<ref>{{cite journal |vauthors=Bernstein C, Johns V |title=Sexual reproduction as a response to H2O2 damage in Schizosaccharomyces pombe |journal=J Bacteriol |volume=171 |issue=4 |pages=1893–7 |date=April 1989 |pmid=2703462 |pmc=209837 |doi=10.1128/jb.171.4.1893-1897.1989 }}</ref>  ''[[Volvox carteri]]'', a haploid multicellular, facultatively sexual green algae, can be induced by heat shock to reproduce by meiotic sex.<ref>{{cite journal |vauthors=Kirk DL, Kirk MM |title=Heat shock elicits production of sexual inducer in Volvox |journal=Science |volume=231 |issue=4733 |pages=51–4 |date=January 1986 |pmid=3941891 |doi=10.1126/science.3941891 |bibcode=1986Sci...231...51K }}</ref>  This induction can be inhibited by [[antioxidant]]s indicating that the induction of meiotic sex by heat shock is likely mediated by [[oxidative stress]] leading to increased DNA damage.<ref>{{cite journal |vauthors=Nedelcu AM, Marcu O, Michod RE |title=Sex as a response to oxidative stress: a twofold increase in cellular reactive oxygen species activates sex genes |journal=Proc Biol Sci |volume=271 |issue=1548 |pages=1591–6 |date=August 2004 |pmid=15306305 |pmc=1691771 |doi=10.1098/rspb.2004.2747 }}</ref>

==Occurrence==
===In life cycles===
[[Image:gametic meiosis.png|thumb|350px|Diplontic life cycle]]
[[Image:zygotic meiosis.png|thumb|350px|Haplontic life cycle.]]

{{Main|Biological life cycle}}
{{See also|Alternation of generations}}

Meiosis occurs in eukaryotic [[biological life cycle|life cycles]] involving [[sexual reproduction]], consisting of the cyclical process of growth and development by [[mitosis|mitotic]] cell division, production of gametes by meiosis and fertilization.  At certain stages of the life cycle, [[germ cell]]s produce gametes. [[Somatic cell]]s make up the body of the organism and are not involved in gamete production.

Cycling meiosis and fertilization events results in  alternation between haploid and diploid states. The organism phase of the life cycle can occur either during the diploid state (''diplontic'' life cycle), during the haploid state (''haplontic'' life cycle), or both (''haplodiplontic'' life cycle), in which there are two distinct organism phases, one with haploid cells and the other with diploid cells.

In the ''diplontic life cycle'' (with pre-gametic meiosis), as in humans, the organism is multicellular and diploid, grown by mitosis from a diploid cell called the [[zygote]]. The organism's diploid germ-line stem cells undergo meiosis to make haploid gametes (the [[spermatozoa]] in males and [[ovum|ova]] in females), which fertilize to form the zygote. The diploid zygote undergoes repeated cellular division by [[mitosis]] to grow into the organism.

In the ''haplontic life cycle'' (with post-zygotic meiosis), the organism is haploid,  by the proliferation and differentiation of a single haploid cell called the [[gamete]]. Two organisms of opposing sex 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 [[Fungus|fungi]] and many [[protozoa]] utilize the haplontic life cycle. {{citation needed|date=January 2011}}

In the ''haplodiplontic life cycle'' (with sporic or intermediate meiosis), 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 produce a new diploid organism. The haplodiplontic life cycle can be considered a fusion of the diplontic and haplontic life cycles.<ref>{{Cite book|url=https://books.google.com/books?id=dOaODP4Oo5kC&q=The+sporic+life+cycle+can+be+considered+a+fusion+of+the+gametic+and+zygotic+life+cycles&pg=PA121|title=An Introduction to Phycology| vauthors = South GR, Whittick A |date=2009-07-08|publisher=Wiley |isbn=978-1-4443-1420-5}}</ref>{{citation needed|date=January 2011}}

===In plants and animals===
[[File:MitosisAndMeiosis en.png|thumb|upright=1.5|Overview of chromatides' and chromosomes' distribution within the mitotic and meiotic cycle of a male human cell]]
Meiosis occurs in all animals and plants. The 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 instead of gametes. When they germinate, these spores undergo repeated cell division by mitosis, developing into a multicellular haploid [[gametophyte]] generation, which then produces gametes directly (i.e. without further meiosis).

In both animals and plants, the final stage is for the gametes to fuse to form a [[zygote]] in which the original number of chromosomes is restored.<ref>{{cite book| vauthors = Bidlack JE, Jansky S, Stern KR |title=Stern's Introductory Plant Biology|year=2011|publisher=McGraw Hill|isbn=978-0-07-304052-3 |oclc=320895017 |pages=214–29}}</ref>

===In mammals===
In females, meiosis occurs in cells known as [[oocyte]]s (singular: oocyte). Each primary oocyte divides twice in meiosis, unequally in each case. The first division produces a daughter cell, and a much smaller polar body which may or may not undergo a second division. In meiosis II, division of the daughter cell produces a second polar body, and a single haploid cell, which enlarges to become an [[egg cell|ovum]]. Therefore, in females each primary oocyte that undergoes meiosis results in one mature ovum and two or three polar bodies.

There are pauses during meiosis in females. Maturing oocytes are arrested in prophase I of meiosis I and lie dormant within a protective shell of somatic cells called the [[ovarian follicle|follicle]]. At the beginning of each [[menstrual cycle]], [[follicle-stimulating hormone|FSH]] secretion from the anterior pituitary stimulates a few follicles to mature in a process known as [[folliculogenesis]]. During this process, the maturing oocytes resume meiosis and continue until metaphase II of meiosis II, where they are again arrested just before ovulation. If these oocytes are fertilized by sperm, they will resume and complete meiosis. During folliculogenesis in humans, usually one follicle becomes dominant while the others undergo [[Follicular atresia|atresia]]. 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 [[centrosome]]s.<ref>{{cite journal | vauthors = Brunet S, Verlhac MH | title = Positioning to get out of meiosis: the asymmetry of division | journal = Human Reproduction Update | volume = 17 | issue = 1 | pages = 68–75 | year = 2010 | pmid = 20833637 | doi = 10.1093/humupd/dmq044 | s2cid = 13988521 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Rosenbusch B | title = The contradictory information on the distribution of non-disjunction and pre-division in female gametes | journal = Human Reproduction | volume = 21 | issue = 11 | pages = 2739–42 | date = November 2006 | pmid = 16982661 | doi = 10.1093/humrep/del122 | doi-access =  }}</ref>

In males, meiosis occurs during [[spermatogenesis]] in the [[seminiferous tubule]]s of the [[testicle]]s. Meiosis during spermatogenesis is specific to a type of cell called [[spermatocyte]]s, which will later mature to become [[spermatozoon|spermatozoa]]. Meiosis of primordial germ cells happens at the time of puberty, much later than in females. Tissues of the male testis suppress meiosis by degrading retinoic acid, proposed to be 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.<ref>{{cite journal | vauthors = Lin Y, Gill ME, Koubova J, Page DC | title = Germ cell-intrinsic and -extrinsic factors govern meiotic initiation in mouse embryos | journal = Science | volume = 322 | issue = 5908 | pages = 1685–7 | date = December 2008 | pmid = 19074348 | doi = 10.1126/science.1166340 | bibcode = 2008Sci...322.1685L | s2cid = 11261341 }}</ref><ref>{{cite journal | vauthors = Suzuki A, Saga Y | title = Nanos2 suppresses meiosis and promotes male germ cell differentiation | journal = Genes & Development | volume = 22 | issue = 4 | pages = 430–5 | date = February 2008 | pmid = 18281459 | pmc = 2238665 | doi = 10.1101/gad.1612708 }}</ref> Genetic loss-of-function studies on retinoic acid-generating enzymes have shown that retinoic acid is required postnatally to stimulate spermatogonia differentiation which results several days later in spermatocytes undergoing meiosis, however retinoic acid is not required during the time when meiosis initiates.<ref name="Teletin" />

In [[Female#Mammalian females|female mammals]], meiosis begins immediately after primordial germ cells migrate to the ovary in the embryo. Some studies suggest that retinoic acid derived from the primitive kidney (mesonephros) stimulates meiosis in embryonic ovarian oogonia and that tissues of the embryonic male testis suppress meiosis by degrading retinoic acid.<ref name="Bowles">{{cite journal | vauthors = Bowles J, Knight D, Smith C, Wilhelm D, Richman J, Mamiya S, Yashiro K, Chawengsaksophak K, Wilson MJ, Rossant J, Hamada H, Koopman P | title = Retinoid signaling determines germ cell fate in mice | journal = Science | volume = 312 | issue = 5773 | pages = 596–600 | date = April 2006 | pmid = 16574820 | doi = 10.1126/science.1125691 | bibcode = 2006Sci...312..596B | s2cid = 2514848 }}</ref> However, genetic loss-of-function studies on retinoic acid-generating enzymes have shown that retinoic acid is not required for initiation of either female meiosis which occurs during embryogenesis<ref>{{cite journal | vauthors = Kumar S, Chatzi C, Brade T, Cunningham TJ, Zhao X, Duester G | title = Sex-specific timing of meiotic initiation is regulated by Cyp26b1 independent of retinoic acid signalling | journal = Nature Communications | volume = 2 | issue = 1 | pages = 151 | date = January 2011 | pmid = 21224842 | pmc = 3034736 | doi = 10.1038/ncomms1136 | bibcode = 2011NatCo...2..151K }}</ref> or male meiosis which initiates postnatally.<ref name="Teletin">{{cite journal | vauthors = Teletin M, Vernet N, Yu J, Klopfenstein M, Jones JW, Féret B, Kane MA, Ghyselinck NB, Mark M | title = Two functionally redundant sources of retinoic acid secure spermatogonia differentiation in the seminiferous epithelium | journal = Development | volume = 146 | issue = 1 | pages = dev170225 | date = January 2019 | pmid = 30487180 | pmc = 6340151 | doi = 10.1242/dev.170225 }}</ref>

=== Flagellates ===
While the majority of eukaryotes have a two-divisional meiosis (though sometimes [[Chiasma (genetics)|achiasmatic]]), a very rare form, one-divisional meiosis, occurs in some flagellates ([[parabasalid]]s and [[oxymonad]]s) from the gut of the wood-feeding cockroach ''[[Cryptocercus]]''.<ref name="raikov" />

==Role in human genetics and disease==
Recombination among the 23 pairs of human chromosomes is responsible for redistributing not just the actual chromosomes, but also pieces of each of them. There is also an estimated 1.6-fold more recombination in females relative to males. In addition, average, female recombination is higher at the centromeres and male recombination is higher at the telomeres. On average, 1 million bp (1 Mb) correspond to 1 cMorgan (cm = 1% recombination frequency).<ref>{{Cite journal|date=2019-01-01|title=Genome and Gene Structure |journal=Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics|pages=53–77|doi=10.1016/B978-0-12-812537-3.00004-4| vauthors = Hegde MR, Crowley MR |isbn=978-0-12-812537-3|s2cid=92480716 }}</ref> The frequency of cross-overs remain uncertain. In yeast, mouse and human, it has been estimated that ≥200 double-strand breaks (DSBs) are formed per meiotic cell. However, only a subset of DSBs (~5–30% depending on the organism), go on to produce crossovers,<ref>{{Cite journal| vauthors = Hunter N |date=2013-01-01|title=Meiosis |journal=Encyclopedia of Biological Chemistry | edition = 2nd |pages=17–23|doi=10.1016/B978-0-12-378630-2.00474-6|isbn=978-0-12-378631-9}}</ref> which would result in only 1-2 cross-overs per human chromosome.

===Nondisjunction===<!-- This section is linked from [[Klinefelter's syndrome]] -->
{{Main|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
* [[Edwards 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
* [[Jacobs syndrome]] – an extra Y chromosome in males.

The probability of nondisjunction in human oocytes increases with increasing maternal age,<ref>{{cite journal | vauthors = Hassold T, Jacobs P, Kline J, Stein Z, Warburton D | title = Effect of maternal age on autosomal trisomies | journal = Annals of Human Genetics | volume = 44 | issue = 1 | pages = 29–36 | date = July 1980 | pmid = 7198887 | doi = 10.1111/j.1469-1809.1980.tb00943.x | s2cid = 24469567 }}</ref> presumably due to loss of [[cohesin]] over time.<ref>{{cite journal | vauthors = Tsutsumi M, Fujiwara R, Nishizawa H, Ito M, Kogo H, Inagaki H, Ohye T, Kato T, Fujii T, Kurahashi H | title = Age-related decrease of meiotic cohesins in human oocytes | journal = PLOS ONE | volume = 9 | issue = 5 | pages = e96710 | date = May 2014 | pmid = 24806359 | pmc = 4013030 | doi = 10.1371/journal.pone.0096710 | doi-access = free | bibcode = 2014PLoSO...996710T }}</ref>

==Comparison to mitosis==
In order to understand meiosis, a comparison to mitosis is helpful. The table below shows the differences between meiosis and mitosis.<ref>{{cite web|title=How Cells Divide|url=https://www.pbs.org/wgbh/nova/miracle/divi_flash.html|work=PBS|publisher=Public Broadcasting Service|access-date=6 December 2012|archive-url=https://web.archive.org/web/20121101033414/http://www.pbs.org/wgbh/nova/miracle/divi_flash.html|archive-date=1 November 2012|url-status=live}}</ref>
{| class="wikitable"
|-
!  !! 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 || Production of gametes (sex cells) in sexually reproducing eukaryotes with diplont life cycle || Cellular reproduction, growth, repair, asexual reproduction
|-
| Where does it happen? || Almost all eukaryotes (animals, plants, fungi, and [[protist]]s);<ref>{{cite journal | vauthors = Heywood P, Magee PT | title = Meiosis in protists. Some structural and physiological aspects of meiosis in algae, fungi, and protozoa | journal = Bacteriological Reviews | volume = 40 | issue = 1 | pages = 190–240 | date = March 1976 | pmid = 773364 | pmc = 413949 | doi = 10.1128/mmbr.40.1.190-240.1976 }}</ref><ref name = raikov>{{cite journal | vauthors = Raikov IB | year = 1995 | title = Meiosis in protists: recent advances and persisting problems | journal =  European Journal of Protistology| volume = 31 | pages = 1–7 | doi=10.1016/s0932-4739(11)80349-4}}</ref> <br />In gonads, before gametes (in diplontic life cycles); <br />After zygotes (in haplontic); <br />Before spores (in haplodiplontic) || All proliferating cells in all eukaryotes
|-
| Steps || Prophase I, Metaphase I, Anaphase I, Telophase I, <br />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
|-
|}

==Molecular regulation==
{{Expand section|date=August 2020}}

How a cell proceeds to meiotic division in meiotic cell division is not well known. [[Maturation promoting factor|Maturation promoting factor (MPF)]] seemingly have role in  frog Oocyte meiosis. In the fungus [[Schizosaccharomyces pombe|''S. pombe'']]. there is a role of MeiRNA binding protein for entry to meiotic cell division.<ref name="Kimble_2011">{{cite journal | vauthors = Kimble J | title = Molecular regulation of the mitosis/meiosis decision in multicellular organisms | journal = Cold Spring Harbor Perspectives in Biology | volume = 3 | issue = 8 | pages = a002683 | date = August 2011 | pmid = 21646377 | doi = 10.1101/cshperspect.a002683 | pmc = 3140684 }}</ref>

It has been suggested that Yeast CEP1 gene product, that binds centromeric region CDE1, may play a role in chromosome pairing during meiosis-I.<ref name="Honigberg_1993">{{cite journal | vauthors = Honigberg SM, McCarroll RM, Esposito RE | title = Regulatory mechanisms in meiosis | journal = Current Opinion in Cell Biology | volume = 5 | issue = 2 | pages = 219–25 | date = April 1993 | pmid = 8389567 | doi = 10.1016/0955-0674(93)90106-z }}</ref>

Meiotic recombination is mediated through double stranded break, which is catalyzed by Spo11 protein. Also Mre11, Sae2 and Exo1 play role in breakage and recombination. After the breakage happen, recombination take place which is typically homologous. The recombination may go through either a double Holliday junction (dHJ) pathway or synthesis-dependent strand annealing (SDSA). (The second one gives to noncrossover product).<ref name="Lam_2014">{{cite journal | vauthors = Lam I, Keeney S | title = Mechanism and regulation of meiotic recombination initiation | journal = Cold Spring Harbor Perspectives in Biology | volume = 7 | issue = 1 | pages = a016634 | date = October 2014 | pmid = 25324213 | doi = 10.1101/cshperspect.a016634 | pmc = 4292169 }}</ref>

Seemingly there are checkpoints for meiotic cell division too. In S. pombe, Rad proteins, S. pombe Mek1 (with  FHA kinase domain), Cdc25,  Cdc2 and unknown factor is thought to form a checkpoint.<ref name="pmid12482912">{{cite journal | vauthors = Pérez-Hidalgo L, Moreno S, San-Segundo PA | title = Regulation of meiotic progression by the meiosis-specific checkpoint kinase Mek1 in fission yeast | journal = Journal of Cell Science | volume = 116 | issue = Pt 2 | pages = 259–71 | date = January 2003 | pmid = 12482912 | doi = 10.1242/jcs.00232 | hdl = 10261/62904 | s2cid = 14608163 | hdl-access = free }}</ref>

In vertebrate oogenesis, maintained by cytostatic factor (CSF) has role in switching into meiosis-II.<ref name="Honigberg_1993"/>

== See also ==
{{col div|colwidth=30em}}
* [[Fertilisation]]
* [[Coefficient of coincidence]]
* [[DNA repair]]
* [[Oxidative stress]]
* [[Synizesis (biology)]]
* [[Biological life cycle]]
* [[Apomixis]]
* [[Parthenogenesis]]
* [[Alternation of generations]]
* [[Brachymeiosis]]
* [[Mitotic recombination]]
* [[Dikaryon]]
* [[Mating of yeast]]

{{div col end}}

== References ==
{{Reflist|30em}}

===Cited texts===
* {{cite book| vauthors = Freeman S |title=Biological Science|url=https://archive.org/details/biologicalscienc00scot|url-access=registration|year=2005|publisher=Pearson Prentice Hall|location=Upper Saddle River, NJ|isbn=978-0-13-140941-5|edition=3rd}}

== External links ==
{{Commons category}}
* [http://www.johnkyrk.com/meiosis.html Meiosis Flash Animation] {{Webarchive|url=https://web.archive.org/web/20100823065031/http://www.johnkyrk.com/meiosis.html |date=2010-08-23 }}
* [http://www.biology.arizona.edu/Cell_BIO/tutorials/meiosis/page3.html Animations from the U. of Arizona Biology Dept.]
* [https://web.archive.org/web/20140308200250/http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/M/Meiosis.html Meiosis at Kimball's Biology Pages]
* [https://web.archive.org/web/20110925004349/http://www.khanacademy.org/video/phases-of-meiosis?playlist=Biology Khan Academy, video lecture]
* [https://web.archive.org/web/20190215050532/http://www.cellcycleontology.org/ CCO] The Cell-Cycle Ontology
* [http://highered.mcgraw-hill.com/olc/dl/120074/bio19.swf Stages of Meiosis animation]
** [https://www.ibiology.org/cell-biology/overview-of-meiosis/ "Abby Dernburg Seminar: Chromosome Dynamics During Meiosis"]

{{Sex (biology)}}
{{Cell cycle}}
{{Chromosome genetics}}
{{Authority control}}

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