Meiosis

Jurg Kohli, University of Berne, Berne, Switzerland

Edgar Hartsuiker, University of Sussex, Brighton, UK
Meiosis is the process leading to formation of the haploid gametes from diploid cells.
Introduction
The essential feature of sexuality is the bringing together of
the genomes of cells from dierent individuals of a given
species. After mixing their genetic information by breaking
and rejoining DNA molecules (homologous recombina-
tion), at least one complete and functional genome is
established again. Prokaryotic organisms achieve this by a
variety of mechanisms whose common feature is that only
parts of the two input genomes are retained in a single
recombinant genome. Eukaryotes have developed meiosis,
a process allowing for full-length pairing of two parental
genomes, their recombination without loss of genes, and
then segregation of the recombined genetic material into
four cells, each with complete haploid sets of chromo-
somes. Eukaryotes, having many chromosomes, achieve
genome variation also by random assortment of the
parental chromosome sets during meiosis.
The Eukaryotic Life Cycle and Meiosis
The body of a multicellular animal (soma) consists mainly
of diploid cells that do not contribute genetic information
to the progeny. Only cells of the germline undergo meiosis,
andformhaploidgametes inthe sexual organs. Incontrast,
no germline is set apart during the development of the
soma of plants and fungi. They dierentiate sexual organs
from somatic cells. Gametes may be the direct products of
meiosis, or dierentiate after further divisions of the
primary products of meiosis.
Despite pronounceddierences, most eukaryotic species
can be accommodated in a common basic life cycle with a
diploid and a haploid phase (Figure 1). Most eukaryotic
species, in particular multicellular organisms, predomi-
nantly use the diploid phase for formation of the soma. A
tendency for haploid soma is found in some multicellular
eukaryotes (e.g. mycelial fungi) and in some unicellular
eukaryotes (e.g. yeasts and algae). Other species have two
dierent types of soma, one in the haploid, the other in the
diploid phase of their life cycle (e.g. mosses). In a life cycle
involving mainly the haploid phase, the zygote formed by
gamete fusion is the only diploid cell. It undergoes meiosis
without intervening mitotic divisions. In contrast, gametes
are the only haploid cells in species where the life cycle is
predominantly in the diploid phase. In higher plants the
haploid cells resulting from meiosis form a small tissue
within the owers of the diploid plant, producing gametes
and other specialized cells.
The Principal Events in Meiosis
The crucial features specic to meiosis assure that each of
the four resulting cells obtains a haploid set of chromo-
somes. These features involve pairing of homologous
chromosomes, crossover (chiasma) formation, and the
reductional meiosis I division. To achieve this, a number of
meiosis-specic processes and structures have developed
(Figure 2). The following overview of meiotic events may
not fully apply to all eukaryotes (see Variations of
meiosis).
Premeiotic DNA replication and sister
chromatid cohesion
Diploid cells ready to undergo meiosis (meiocytes) are
specically dierentiated. This dierentiation is completed
at the latest in the G
1
phase immediately before premeiotic
DNA replication. As in the S phase of mitotic cells,
cohesion of sister chromatids is established during
premeiotic DNA replication. This is achieved by protein
complexes (cohesins) attaching to a number of sites along
the sister chromatids (Figure 2a, top). In meiosis, sister
chromatid cohesion contributes to proper pairing and
recombination of the chromosomes during prophase. In
addition, sister chromatid cohesion is essential for correct
completion of meiosis I and II.
Prophase I: leptotene, zygotene and
pachytene
After DNA replication, the pairing of homologous
chromosomes is initiated. Typically, homologous chromo-
some pairing occurs in two distinctive steps: chromosome
alignment and then chromosome synapsis. At early
leptotene the chromosomes become visible as threads with
their ends attached to the nuclear envelope. During
leptotene the homologous chromosomes approach each
Article Contents
Introductory article
. Introduction
. The Eukaryotic Life Cycle and Meiosis
. The Principal Events in Meiosis
. Variations of Meiosis andits Study inModel Organisms
. Regulation of Meiosis
. Summary
1 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
other and align in roughly parallel fashion. It is thought
that this alignment results froma number of close contacts
between homologous DNAsequences on the two chromo-
somes. In addition, the axial elements polymerize along
each of the duplicated chromosome (Figure 2b, top). Axial
elements are assumed to organize the sister chromatids for
maintenance of contacts between the homologous DNA
sequences. Knob-like structures, called early recombina-
tion nodules, are found attached to the axial elements.
Early nodules may be involved in the formation of close
contacts. From leptotene onwards the chromosomes
shorten and thicken (chromatin condensation).
After mitosis, the chromosomes are organized in the
Rabl conguration in many species (Figure 2c). The
centromeres of the chromosomes are clustered and located
at the nuclear surface near the centrosome. Early inmeiotic
prophase (leptotene and zygotene) the bouquet congura-
tion is often observed (Figure 2c). In this conguration the
telomeres of the chromosomes are clustered at the nuclear
membrane near the centrosome. It is likely that the
bouquet contributes to homologous chromosome pairing
and formation of the synaptonemal complex (SC, see
Figure 2d). SC formation is initiated early in zygotene and
often starts near to the telomeres. The zippering-up of the
homologous chromosomes occurs by attachment of the
transverse laments to the axial elements. The transverse
laments overlap in the middle between the axial elements.
In the SC, axial elements are also referred to as lateral
elements. The overlap region of the transverse laments is
often visible as the central element running between the
two axial elements and may contain additional proteins.
The formation of the SC is accompanied by resolution of
the bouquet and further condensation of the chromo-
somes. A pair of homologous chromosomes organized by
the SC over their whole length is called a bivalent.
Chromosome synapsis is completed in pachytene. Another
type of recombination nodule is attached to the fully
developed SCs later in pachytene. These late nodules are
larger and occur in lower numbers than the early nodules.
Prophase I: recombination
Pairing of homologous chromosomes is required for
recombination, which occurs at much higher frequencies
during meiosis than in mitotically dividing diploid cells.
Individual recombination events only occur between two
chromatids of dierent parentage within the bivalents.
Two types of recombination events are distinguished in
crosses of strains with heterozygous genetic markers:
conversion and crossover (Figure 3). To describe them, it
is useful torecall that the bivalents consist of a total of eight
DNA single strands making up four DNA double helices.
Before recombination occurs, there are thus two wild-type
chromatids and two mutant chromatids at the hetero-
zygous marker sites (a, b, c in Figure 3). Without
recombination, wild-type ( 1) and mutant ( 2) DNA
sequences segregate 2 1 : 2 2 (DNA double helices) or
4 1 : 4 2 (DNAsingle strands) intothe four haploidnuclei
resulting from meiosis.
Conversions are nonreciprocal transfers of genetic
information from one chromatid to another. One type is
half-chromatid conversion, for example 5 1 : 3 2
segregation (marker b in Figure 3). The recombinant
chromatid carries hybrid DNA at the site of the genetic
marker. In hybrid DNA, normal base pairing (A-Tand G-
C) is absent at the site of heterozygosity. Instead,
mismatches of bases (e.g. A/A) are present. Half-chroma-
tid conversion events are also called postmeiotic segrega-
tion events, since the next DNAreplication will resolve the
hybrid DNA into two dierent chromatids: one with 1,
F
u
sion + Karyoga
m
y
R
e
p
lication + Meio
sis
M
i tosis
R
e
pli catio
n
Diploid phase (2n)
Diploidization
Haploidization
R
e
pli catio
n
M
i tosis
Haploid phase (n)
Figure1 The eukaryotic life cycle. Sexuallyreproducingeukaryotes havea life cycle withalternatingdiploidandhaploidphases. Diploidcells (2n) that
have differentiated to undergo meiosis performtwo divisions after a single round of DNAreplication. The four resulting haploid cells carry the basic set of
chromosomes characteristic for each species (n). The haploid products of meiosis differentiate into gametes directly, or an intervening phase of mitotic
divisions may occur before gamete formation. Twogametes of different matingtype (red versus blue) fuse to a diploidcell, the zygote, whichmay enter a
phase of mitotic divisions, or undergo meiosis directly.
Meiosis
2 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
the other with 2information. The occurrence of post-
meiotic segregation indicates that hybrid DNA is a
frequent, if not obligatory, intermediate of genetic
recombination. It is formed by transfer of a DNA single
strand from one chromatid (donor) to another (acceptor).
An example of full-chromatid conversion is the 6 1 : 2 2
segregation shown for marker b in Figure 3. Most full-
chromatid conversions also seem to result from hybrid
DNA by repair of mismatches to a normal base pair (e.g.
A/A to A-T). Full-chromatid conversion occurs when the
(a)
Sister
chromatids
Cohesins
Centromeres
Synaptonemal
complex
Crossover
Homologous
chromosomes
Axial elements
Early nodule
Late nodule
(b)
Central
element
Rabl Bouquet
(c) Centrosome Telomere Centromere
Recombination
nodule
Chromatin
loops
Central
region
Axial elements (d)
Centromeres
Figure 2 Meiosis. The schematic drawings represent the crucial features of meiosis. In (a) the emphasis is on the fate of the two sets of chromatids
resulting frompremeiotic DNA replication. Each red and blue line represents a double helix of DNA. (b) Schematic representation of the behaviour of
chromosomes as visualized by light and electron microscopy. In (c) the organization of chromosomes in the nucleus after mitosis (Rabl) is compared with
the chromosome configuration during chromosome pairing in early meiotic prophase (Bouquet). (d) The synaptonemal complex. The two axial elements
organize the sister chromatids, and the transverse filaments assure synapsis.
Meiosis
3 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
repair enzymes conserve the DNA sequence of the single
strand that invaded the chromatid during hybrid DNA
formation. Tothe left andright of the site of conversionthe
recipient chromatid remains unchanged. In consequence,
conversion contributes to the variation of genomes, the
basis for evolution by selection. But, in contrast to the
crossovers, conversion events do not assure proper
segregation of chromosomes in the meiotic divisions.
For the observationof crossover events, it is necessary to
followat least two heterozygous markers in genetic crosses
(a andc inFigure3). Whena crossover occurs betweena and
c in the cross a
1
b
1
c
1
a
2
b
2
c
2
, the two reciprocal
recombinants a
1
c
2
and a
2
c
1
are formed. Supercially,
crossovers can be perceived as breakage of the two
chromatids involved, exchange of the free ends, and
reunion to form intact chromatids again. The whole
chromatid parts anking the crossover site are exchanged
(Figures 2a and 3). Crossovers are often, if not always,
associated with conversion of sequences at the point of
breakage and reunion (as shown for marker b in Figure 3).
Thus, mechanistic models assume that conversions and
crossovers originate from the same recombination initia-
tion events.
The formation of hybrid DNA as an intermediate for
crossover and conversion requires that at least single
strands of DNA in the participating chromatids are cut by
endonucleases. However, in the yeast Saccharomyces
cerevisiae DNA double-strand breaks were discovered as
initiating events of meiotic recombination. Whether
double-strand breaks are also the initiation events in other
organisms remains to be investigated. In S. cerevisiae the
double-strand breaks clearly occur before SC formation,
but completed crossovers are only detectable at resolution
of the SC. The double-strand cutting enzyme has been
identied. When it is inactivated by mutation, SC
formation does not occur. When the corresponding genes
are inactivated in Caenorhabditis elegans or in Drosophila
melanogaster, SC formation still occurs. It remains to be
seen whether the SC is required for initiation of recombi-
nation in these organisms.
Evidence suggests that the more frequently observed
early recombination nodules are involved in initiation
leading to conversion events. The late recombination
nodules occurring with lower frequency may be involvedin
maturing a subset of the recombination intermediates to
crossovers. Crossovers are not randomly distributed along
the bivalents. Crossovers close to each other are observed
at lower frequencies than expected from random distribu-
tion, a phenomenon known as crossover interference.
Eukaryotic genomes contain repeated DNA sequences
located on nonhomologous chromosomes. Thus, a check-
ing mechanism of early homologous contacts must exist in
order to avoid crossover formation between DNA
sequence repeats located on nonhomologous chromo-
somes. When such ectopic crossovers are not excluded,
reciprocal translocation of chromosomes occurs fre-
quently, and gametes with defective genomes result.
Ectopic conversion does not lead to chromosome rearran-
gement, and it is observed in appropriate experimental
systems.
Prophase I: diplotene and diakinesis
The transition from pachytene to diplotene involves
degradation of the SC, including the axial elements. As a
consequence the two chromatids of each homologous
chromosome become visible as separate threads. Never-
theless, sister chromatid cohesion is still operative. The
homologous chromosomes belonging toa bivalent are now
held together by microscopically visible cross-shaped
structures, the chiasmata (singular, chiasma). Chiasmata
form at the sites of crossovers (Figure 2a and Figure 2b). At
least one chiasma is required per bivalent to ensure proper
chromosome segregation at meiosis I. Absence of chiasma
formation, as well as absence of sister chromatid cohesion
during prophase I, leads to defective chromosome segrega-
a
+
b
+
c
+
a

a
+
b
+
c
+
a

a
+
b
+
c
+
a

a
+
b
+
c
+
a

5+ : 3
No crossover
6+ : 2
No crossover
6+ : 2
Crossover
Figure3 Recombination. The four chromatids of a bivalent resultingfrom
premeiotic DNA replication are drawn schematically as DNA double
helices. Thus, there are eight DNA single strands. At the three genetic
markers a, b, and c different DNA sequences are present in the two
homologous chromosomes: 1is wild-type sequence, 2is mutant
sequence. Three examples of recombinationproducts areshown. The 51 :
32 tetradfor marker bis the result of half-chromatidconversionleadingto
postmeiotic segregation. The 61 : 22 tetrad for marker b derives from
full-chromatid conversion. The third recombination event is again a 61 :
22 segregation, but in this case associated with a crossover. The flanking
markers a and b have exchanged reciprocally, resulting in a
1
c
2
and a
2
c
1
recombinants.
Meiosis
4 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
tion. The following stage, diakinesis does not dier much
from diplotene, except for increased chromosome con-
densation.
Meiosis I
At the beginning of metaphase I the centrosome divides
and a spindle forms between the two centrosomes now
located at opposite poles of the meiocyte. The bivalents
arrange in the equatorial plane between the spindle poles.
In contrast to mitosis, the centromeres of the homologous
chromosomes do not visibly split during meiosis I division.
Control mechanisms ensure that the two centromeres of
each bivalent are attached to spindle bres connecting to
opposite poles of the spindle. When all the bivalents are
correctly attached and aligned in the metaphase plate, the
spindle starts pulling the members of each bivalent to the
opposite poles. Then, at anaphase I, the cohesion of the
sister chromatids out in the chromosome arms is released.
This allows resolution of the chiasmata, and the homo-
logous chromosomes separate from each other. The two
daughter nuclei forming in the pole regions of the meiosis I
spindle carry haploid sets of chromosomes. For this reason
meiosis I is also called reductional division. Each chromo-
some still consists of two chromatids that are rmly
attached to each other at the centromere. Some of the
chromatid arms are recombinant as a result of the
crossovers (Figure 2a).
Meiosis II
Because it is, in some respects, similar to mitosis, meiosis II
is also called the equational division of meiosis. Unlike
mitotically dividing cells, no DNA replication occurs
before formation of the meiosis II spindles. When the
chromosomes arrange in the metaphase II plates, the
structure of the centromeres is altered in comparison to
meiosis I. As in mitosis, spindle bres from opposite poles
attach to the centromeres of each chromosome. The
centromeres then split to allow transport of the individual
chromatids to the poles. In further contrast to mitotic
metaphase, sister chromatidcohesionout inthe arms of the
chromosomes is absent at metaphase II. Thus, the
mechanisms ensuring proper segregation in meiosis II
may dier from those of mitotic divisions. Proteins have
been identied that are located to the bivalent arms during
prophase I but these relocate to the centromeres before the
reductional division occurs. They persist there up to
metaphase II and are likely to be involved in proper
reorganization and cohesion of the centromeres. The four
primary products of meiosis then dierentiate in various
ways in dierent species.
Variations of Meiosis and its Study in
Model Organisms
For a thorough analysis of all aspects of meiosis, the
existence of well-developed classical and molecular genet-
ics (including genome sequences) is mandatory. The
accessibility of meiocytes for cytological analysis at all
stages, and the opportunity to isolate them in large
numbers is also important.
Yeasts and other fungi
Ascomycetes are uniquely suited for meiosis research.
Meiosis results in four ascospores that are transiently
retained within a membrane, the ascus. In some species an
additional mitosis occurs to form asci with eight spores.
These are resistant to adverse environmental conditions,
act as vehicles for spreading the species, and germinate to
formvegetative cells under suitable growthconditions. The
spores of individual asci can be studied separately (tetrad
or octad analysis), providing information fromcrosses not
accessible in most other eukaryotes. Ascobolus immersus,
Aspergillus nidulans, Neurospora crassa, and Sordaria
brevicollis are species of mycelial fungi with eight-spored
asci. Their analysis was instrumental for establishing
mechanistic models on recombination, and continues to
contribute valuable data.
The unicellular yeasts Saccharomyces cerevisiae and
Schizosaccharomyces pombe are highly suitable model
organisms for the investigation of meiosis, and have been
intensely studied. These form asci with four spores.
Diploid and haploid strains of both yeasts can be
propagated mitotically. S. cerevisiae prefers the diploid
phase for vegetative growth, and meiosis is induced by
starvation for nutrients. All in all, meiosis and recombina-
tion in S. cerevisiae is understood better than in any other
eukaryote. Initiation of recombination (DNA double-
strandbreaks) andintermediates of recombination(hybrid
DNA, Holliday structures), as well as completed recombi-
nation events (conversions and crossovers) are accessible
to physical analysis. Tools exist for the analysis of sister
chromatid cohesion, chromosome pairing, the SC, and
chromosome segregation. A large number of genes
involved in all aspects of meiosis have been identied by
mutational screens. Many more genes are currently
identied in the completed genome sequence, and their
function has been studied by reverse genetics and protein
biochemistry.
The ssion yeast S. pombe uses the haploid phase in its
life cycle. The mating of cells (zygote formation) and the
immediately following meiosis are induced by starvation
for nutrients. In addition, diploid strains can also be
induced to undergo meiosis. An interesting feature of S.
pombe is its small number of chromosomes (n 53). A fully
developed SCis not formed, but laments resembling axial
Meiosis
5 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
elements of other organisms are present and functionally
important. Concomitant absence of a fully developed SC
and of crossover interference has been observed in S.
pombe and in A. nidulans. Thus, full SC formation is not
required for proper recombination and chromosome
segregation in these organisms. In S. pombe the bouquet
structure and extensive nuclear movement is maintained
throughout prophase I.
Multicellular eukaryotes and sexual
dimorphism
Zygotes are formed by two gametes of dierent mating
type (Figure 1). In lower eukaryotes the dierent gametes
are usually morphologically similar. In contrast, the male
and female gametes of animals and plants dier; they are
formed in morphologically dierent sexual organs, and the
processes of male and female meiosis dier as well. In
general, the motile male gametes are of small size, and
produced in large numbers. The nonmotile female gametes
(eggs) are often large, and form in small numbers.
Recombination and meiosis have been studied in a large
number of higher plants, including lily, maize, tomato,
wheat, and other cereals. The four microspores resulting
directly from male meiosis are all functional and undergo
further divisions during formation and outgrowth of the
pollen grains. Two spermcells are formedfromeach pollen
grain. Only one of the four haploid products of female
meiosis survives. It gives rise to eight cells by three rounds
of divisions. One of them becomes the egg cell that is
fertilized by one of the sperm cells. The fertilized egg
develops to become the embryo of the seed. Two other
haploid cells of the female tissue fuse. The resulting diploid
cell is fertilized by the secondspermcell toformthe triploid
endosperm, another component of the seed. Since Arabi-
dopsis thaliana is now the most widely used model plant, it
is rapidly gaining importance for the advanced study of
plant meiosis.
The work on meiosis and recombination in a vast
number of dierent animals is beyond the scope of this
article. Several marine invertebrates, including sea urchins
and starsh, provide unique advantages for analysis of
specic aspects of meiosis, gamete development, and
fertilization, because they produce large numbers of male
and female gametes that are amenable to experiments in
vitro. Oocyte maturation and fertilization are investigated
extensively at cellular and molecular levels in the amphi-
bian Xenopus laevis. Common to animals is the production
of large numbers of sperm that extensively dierentiate
after completion of meiosis to acquire motility and to
reduce cell volume.
A frequent phenomenon in invertebrates and verte-
brates is the long time needed for development of the
mature egg. Germline cells often dierentiate and initiate
meiosis during embryogenesis of the females. But then
progress of meiosis is arrested at prophase I until sexual
maturity is reached. In mammals, this developmental
arrest may last for several decades. Eventually individual
oocytes are released from arrest and mature. After release
of the meiocytes from the prophase I arrest, they grow and
proceed with meiosis to a second arrest at the mature
oocyte stage. Depending on the species, the second arrest
may occur at diakinesis, metaphase I, metaphase II, or
after completion of meiosis II. Release from the second
arrest is triggeredby fertilizationof the egg by sperm. Thus,
female meiosis is completed in many cases only after
fertilization has occurred. One (fertilization at metaphase
II) or two (fertilization at metaphase I) of the resulting
nuclei are discarded by extrusion from the egg as polar
bodies. This peculiar feature means that the fertilizing
sperm may inuence the segregation of female chromo-
somes, namely retention in the egg as opposed to inclusion
in the polar bodies. This phenomenon, meiotic drive,
accounts for distortions of mendelian inheritance.
The nematode Caenorhabditis elegans and the y
Drosophila melanogaster are excellent model organisms for
the study of meiosis. C. elegans with its completely mapped
developmental lineage of all body cells is ideally suited for
the study of germline development, the dierentiation of
meiocytes, and the contribution of somatic cells to these
processes. Spindle bres attach to many sites along the
chromosomes in nematode mitosis (holocentric chromo-
somes). But in meiosis, the chromosome ends serve as
monocentric attachment sites for the microtubules. Cross-
overs are distributed along the whole chromosomes, but the
early events of chromosome pairing depend on sites that are
located toward one end of the chromosomes (homologue
recognition regions). Mutations in dierent genes were
shown to dierentially aect frequency and distribution of
crossovers in dierent chromosomes.
Crossovers were rst discovered and applied to the
genetic mapping of chromosomes in D. melanogaster. A
large collection of mutants and advanced cytological and
reverse genetics methods are at hand. Standard SC
formation and recombination is observed for the large
chromosomes in female meiosis, but not for the smallest
chromosome. In male meiosis, SC formation and recom-
bination are absent for all chromosomes. These ndings
led to the characterization of alternative (achiasmate)
mechanisms ensuring chromosome segregation in male
and female meiosis. They also involve pairing of homo-
logous chromosomes. DNAsequences requiredfor pairing
in male prophase have been recently identied.
The primary mammalian model organism is the mouse.
By obtaining transgenic mice, meiotic phenotypes resulting
from designed mutations can be observed directly. Cytolo-
gical and biochemical analysis of male and female meiosis is
performed on gonad tissues and cell lines from a variety of
mammals. A large number of genes have been identied in
mammalian species, including humans, that are homolo-
gous to genes known to be important for meiosis in the
Meiosis
6 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
model organisms described above. The correlation of newly
identied mammalian genes with sterility and other
reproduction disorders is gaining momentum.
Regulation of Meiosis
The mechanism of meiosis ensures the production of
functional gametes. To this end, regulatory mechanisms
intrinsic to the meiocytes ensure that the programme of
necessary steps is executed properly. These intrinsic
mechanisms also respond to extrinsic factors that originate
from the environment of the meiocytes. In multicellular
organisms, such extrinsic signals could originate from the
somatic cells associated with the meiocytes, or they could
be hormones released from cells far from the gonads.
Intrinsic regulation of meiosis
Successful completionof anevent may initiate the next step
in a given programme, or trigger a step in another of the
meiosis subprogrammes running in parallel. If a step
subject to control is not completed, surveillance mechan-
isms (checkpoints) will inhibit downstream steps. In S.
cerevisiae recombination intermediates must be resolved
for meiosis I to occur. The checkpoint in question shares
proteins with a mitotic checkpoint that controls repair of
damaged DNA as a condition for progress towards
mitosis. A checkpoint in grasshopper spermatocytes is
well characterized. It ensures that progression from
metaphase to anaphase I does not occur unless all the
bivalents are attached stably tomicrotubules connecting to
both poles of the spindle. This checkpoint mechanism
measures the tension applied to the chromosomes by the
pulling spindle.
It is apparent now that the M phase-promoting factor
(MPF), consisting of the proteins Cdc2 and cyclin B, plays
a central role in the control of mitotic and meiotic cell
divisions in all eukaryotes. In fact, MPF was discovered as
a meiosis regulator in Xenopus oocytes. In part, meiotic
regulation mechanisms work through the same signal
transduction pathways that are involved in mitotic events.
Nevertheless, a large number of proteins are expressedonly
in meiosis or in subsequent dierentiation processes, e.g.
ascospore and spermatocyte formation. The investigation
of these regulation processes is being actively pursued in
model organisms and in human cells.
Regulation and gamete formation in
mammals
Proliferation of the germline cells occurs during male and
female gonad development. Some of the cells dierentiate
to become meiocytes, while others undergo programmed
cell death (apoptosis). This may be an additional surveil-
lance mechanismfor elimination of cells no longer suitable
for meiosis. The primary meiocytes are enclosedinlayers of
specically dierentiated somatic cells, the Sertoli cells in
males, and the multilayer granulosa cells in females.
Exchange of signals with these somatic cells is essential
for gamete formation.
Undierentiated male germline cells keep dividing
throughout the adult stage, allowing the continuous
production of large numbers of spermatocytes. Meiosis
occurs in an uninterrupted sequence of events. Only
afterwards does the extensive dierentiationof the primary
meiotic products to mature spermatocytes take place.
Prominent features include the extreme condensation of
DNAwith the help of associated sperm-specic proteins in
the nucleus, and formation of the tail requiring massive
restructuring of the cytoplasm.
In females a xed number of primary meiocytes is
formed, meiosis is initiated, but thenarrestedinprophase I.
Maintenance of this arrest over a long time requires
rigorous control mechanisms. When the primary follicles
are activated, it is the cytoplasmic growth and dierentia-
tion which occurs rst. This leads to accumulation of
macromolecules which are required for the cell divisions
after fertilization. It seems that release from the nuclear
prophase I arrest is triggered by reduction of cyclic
adenosine monophosphate (cAMP) concentration. Acti-
vation of MPF leads to meiosis I, which is followed by the
second arrest before meiosis II. Fertilization triggers
calcium oscillations leading to extrusion of the second
polar body. Inactivation of MPF marks the completion of
meiosis, and is required for initiation of the mitotic
divisions starting embryogenesis.
Summary
Meiosis is essential for the sexual reproduction of eukar-
yotic organisms. Important practical aspects of meiosis
research are the investigation of infertility and other
disorders related to sexual development, as well as the
improvement of breeding methods for animals and plants.
Further Reading
Hecht NB (1998) Molecular mechanisms of male germ cell dierentia-
tion. BioEssays 20: 555561.
Heikinheimo O and Gibbons WE (1998) The molecular mechanisms of
oocyte maturation and early embryonic development are unveiling
newinsights into reproductive medicine. Molecular Human Reproduc-
tion 4: 745756.
John B (1990) Meiosis. Cambridge, UK: Cambridge University Press.
Kleckner N (1996) Meiosis: How could it work? Proceedings of the
National Academy of Sciences of the USA 93: 81678174.
Page AW and Orr-Weaver TL (1997) Stopping and starting the meiotic
cell cycle. Current Opinion in Genetics and Development 7: 2331.
Roeder GS (1997) Meiotic chromosomes: it takes two to tango. Genes
and Development 11: 26002621.
Meiosis
7 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net