Editing Meiosis (section)

==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).

<div class="skin-invert-image">{{wide image|Meiosis Stages.svg|1100px|Diagram of the meiotic phases}}</div>

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''', the disappearance of the nucleoli and the [[nuclear envelope]] is seen 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.