Meiosis or Reduction division

The term Meiosis is derived from Greek word ‘meio’ which means lessen and was coined by J B Farmer
and J.E.S. Mooree in 1905. Meiosis is a special type of cell division (reduction division) for sexual
reproduction in eukaryotes such as animals, plants and fungi, resulting in four daughter cells each with
half the number of chromosomes that of the parents. In this division the number of sets of chromosomes
reduced to half the original number, typically from two sets (diploid) to one set (haploid). It occurs in
meiocytes eg. germ (sex) cells or in gonads (testes and ovaries) during gamete formation. Meiosis
preceded by duplication of chromosomes which is followed by meiosis I and meiosis II.

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 worms’ 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 observed
crossover in Drosophila melanogaster meiosis and provided the first genetic evidence that genes are
transmitted on chromosomes.
Meiosis (Gr. Meiouni = to reduce; sis = process) has been reported for the first time by J. B. Farmer and J.B
Moore (1905).

MPF Promotes Maturation of Oocytes and Mitosis in Somatic Cells

The process of oocyte maturation, from G2-arrested oocyte to the egg arrested in metaphase of meiosis II,
can be studied in vitro by surgically removing G2-arrested oocytes from the ovary of an adult female frog
Xenopus laevis and treating them with progesterone. When cytoplasm from eggs arrested in metaphase of
meiosis II is microinjected into G2-arrested oocytes, the oocytes mature into eggs in the absence of
progesterone. This system not only led to the initial identification of a factor in egg cytoplasm that
stimulates maturation of oocytes in vitro in the absence of progesterone but also provided an assay for this
factor, called maturation-promoting factor (MPF). MPF turned out to be the key factor that regulates the
initiation of mitosis in all eukaryotic cells.

Figure 13-5. In vitro maturation of Xenopus oocytes and assay of maturation-promoting factor (MPF)
(a) Treatment of G2-arrested Xenopus oocytes with progesterone stimulates them to proceed through
meiosis I, interphase, and the first half of meiosis II before arresting in the metaphase of meiosis II. Three
pairs of duplicated homologous chromosomes (blue) connected to mitotic spindle microtubules (red) are
shown schematically to represent metaphase cells. After addition of sperm and fertilization, fertilized eggs
complete meiosis II. The resulting haploid egg nucleus fuses with the haploid sperm nucleus to produce a
diploid zygote, which undergoes the first of 12 synchronous early embryonic cleavages. (b) When cytoplasm
from unfertilized eggs arrested in metaphase of meiosis II is injected into G2-arrested oocytes, the oocytes
mature into eggs in the absence of progesterone. This process can be repeated multiple times without further
addition of progesterone. [See Y. Masui and C. L. Markert, 1971, J. Exp. Zool. 177:129.]

Using the microinjection system to assay MPF activity at different times during oocyte maturation in vitro,
researchers found that untreated G2-arrested oocytes have low levels of MPF activity; treatment with
progesterone induces MPF activity as the cells enter meiosis I. As the cells enter the interphase between
meiosis I and II, MPF activity falls; it then rises as the cells enter meiosis II and are arrested. Following
fertilization, MPF activity falls again until the zygote (fertilized egg) enters the first mitosis of embryonic
development. All the cells in early frog embryos undergo 12 synchronous cycles of mitosis. Throughout
these cycles MPF activity is low in the interphase periods between mitoses and then rises as the cells enter
mitosis.
Although initially discovered in frogs, MPF activity has been found in mitotic cells from all species assayed.
For example, cultured mammalian cells can be arrested in mitosis by treatment with compounds (e.g.,
colchicine) that inhibit assembly of microtubules. When cytoplasm from such mitotically arrested
mammalian cells was injected into G2- arrested Xenopus oocytes, the oocytes matured into eggs; that is, the
mammalian somatic mitotic cells contained a cytosolic factor that exhibited frog MPF activity. This finding
suggested that MPF controls the entry of mammalian somatic cells into mitosis as well as the entry of frog
oocytes into meiosis. When cytoplasm from mitotically arrested mammalian somatic cells was injected into
interphase cells, the interphase cells entered mitosis; that is, their nuclear membranes broke down into small
vesicles and their chromosomes condensed. Thus MPF is the diffusible factor, first revealed in cell-fusion
experiments that promotes entry of cells into mitosis. Conveniently, the acronym MPF also can stand for
mitosis-promoting factor, a name that denotes the more general activity of this factor.

Because the assay for MPF is cumbersome, several years passed before MPF was purified by column
chromatography and the MPF proteins were characterized. MPF is in fact one of the heterodimeric
complexes composed of a cyclin and cyclin-dependent protein kinase (Cdk) now known to regulate the
cell cycle. Each MPF subunit was recognized through different experimental approaches.

Meiosis
Meiotic division occurs in two stages, meiosis I and meiosis II.
Meiosis I: The first stage begins with a diploid cell that has two copies of each type of chromosome, one
from each the mother and father, called homologous chromosomes. All homologous chromosomes pair up
and may exchange genetic material with each other in a process called crossing over. Each pair then
separates as two haploid cells are formed, each with one chromosome from every homologous pair.
Meiosis II: In the second stage, each chromosome splits into two, with each half, called a sister chromatid,
being separated into two new cells, which are still haploid. Therefore from each original cell, four
genetically distinct haploid cells are produced. These cells can mature into gametes.

MEIOSIS I
In Meiosis I, the pairs of homologous chromosomes, made up of two sister chromatids are split into two
cells. The resulting daughter cells contain one entire haploid set of chromosomes. The first meiotic division
reduces the ploidy of original cell. It produces two haploid cells. Hence meiosis-I is referred to as a
reductional division.
Meiosis I consists of four stages namely, Prophase I (Leptotene, Zygotene, Pachytene, Diplotene,Diakinesis),
Metaphase I, Anaphase I and Telophase I.

Prophase I
It is the first and longest stage of meiosis I. During prophase I, chromosomal cross over occurs resulting in
homologous recombination whereby DNA is exchanged between homologous chromosomes.
Homologous recombination of DNA which occurs in Meiosis I, results in significant genetic variations. It
includes 5 sub stages as follows,
Leptotene
The first stage of prophaseI 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—change from the diffuse state they exist in during the cell’s period of growth and gene
expression, and condense into visible strands within the nucleus. However the two sister chromatids are still
so tightly bound that they are indistinguishable from one another. During leptotene, lateral elements of the
synaptonemal complex assemble. The synaptonemal complex (SC) is a protein structure that forms between
homologous chromosomes (two pairs of sister chromatids) during meiosis and is thought to mediate
chromosome pairing, synapsis, and recombination. 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. 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 stage, also known as pachynema, from Greek words meaning "thick threads", 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 in anaphase I.
In human fetal oogenesis all developing oocytes develop to this stage and stop before birth. This suspended
state is referred to as the dictyotene stage and remains so until puberty.
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. During diakinesis the chiasma
moves from the centromere towards the end of the chromosomes and the intermediate chiasmata diminish.
This type of movement of the chiasmata is known as terminalization.
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.
Metaphase I
Homologous pairs move together along the metaphase plate: As kinetochore microtubules from both
centrioles attach to their respective kinetochores, the 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.

Anaphase I
Kinetochore (bipolar spindles) microtubules shorten, severing the recombination nodules and pulling
homologous chromosomes apart. Since each chromosome has only one functional unit of a pair of
kinetochores, whole chromosomes are pulled toward opposing poles, forming two haploid sets. Each
chromosome still contains a pair of sister chromatids. During this time disjunction occurs, which is one of
the processes leading to genetic diversity as each chromosome can end up in either of the daughter cells.
Nonkinetochore microtubules lengthen, pushing the centrioles farther apart. The cell elongates in
preparation for division down the center.

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.
Crossing over and independent assortment are responsible variability during meiosis. Crossing overs
between homologous chromosomes cause the reassortment of genes in individual chromosome. Independent
assortment of maternal and paternal homologs is occurred during the metaphase of first meiotic division. It
produces 2n different haploid gametes of an organism with n chromosomes.
MeiosisII
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. Centrioles divide and 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 (centrioles) at each pole. 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, where the centromeres are cleaved, allowing microtubules attached to the
kinetochores to pull the sister chromatids apart. 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 uncoiling and
lengthening of the chromosomes and the disappearance of the spindle. The endoplasmic reticulum forms the
nuclear envelope around the chromosomes and the nucleolus reappears due to synthesis of ribosomal RNA
(rRNA) by ribosomal DNA (rDNA) and also due to accumulation of ribosomal proteins.
After the karyokinesis, in each haploid meiotic cell, the cytokinesis occurs and, thus, four haploid cells are
resulted. These cells have different types of chromosomes due to the crossing over in the prophase I.
Meiosis is now complete and ends up with four new daughter cells.

SIGNIFICANCE OF MEIOSIS
Adapting to the constant changing environment and ability to colonize in new environments are the keys for
the long-term survival of a species. To attain these goals it is necessary for the offsprings to be different
from their parents and also different from each other. Meiotic cell division helps in achieving these
objectives in the following ways:
Maintain constant chromosome number
Sexual reproduction involves production of special sex cells called gametes, which further fuse together to
produce a new organism. In this case each gamete must contain half the number of chromosomes of the
parent. It is therefore essential that a reductional division occurs at this stage of the life cycle of the sexually
reproducing organisms.
Thus, meiosis helps in maintaining constant chromosome number. Consequently from a diploid cell, haploid
gametes are produced which in turn unite to form a diploid zygote cell.
Recombination of genes
During Prophase I of Meiosis, equivalent portions of homologous chromosomes are exchanged and in this
way new genetic recombination are produced. Genetic recombination is essential to the process of evolution.
The varied stock of individuals produced as a result of meiosis permit natural selection of best suited species.
Creation of genetic variation
During Metaphase I of Meiosis, pairs of homologous chromosomes randomly arrange themselves on the
equatorial plate. Though each one of the pair determines the same general features, they differ in detailed
features. The random distribution and consequent independent assortment of these chromosomes produces
new genetic combinations.