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Meiosis

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Meiosis
Maj A Hultén, University of Warwick, Coventry, UK
Based in part on the previous version of this Encyclopedia of Life Sciences
(ELS) article, Meiosis by Charles Tease and Maj A Hultén.
Meiosis is a specialised type of cell division, the principal
function of which is to produce spores/gametes (sperm
and eggs in mammals) that have the haploid number of
chromosomes. In humans, this represents a reduction
from 46 (23 pairs) to 23 chromosomes (one complete set)
in sperm and eggs. The normal somatic number of 46
chromosomes is restored at fertilisation. The most com-
plex part of meiosis (prophase I) involves intimate pairing
and synapsis of the homologous chromosomes followed
by reciprocal recombination/crossing-over/chiasma for-
mation. In most organisms, chiasma formation is obliga-
tory to allow the regular segregation of the (rearranged)
homologues at the first (reductional) division (anaphase
I). In mammals, there are substantial differences between
the two sexes as regards the meiotic process. Mammalian
female prophase I takes place during foetal development,
and the second meiotic cell division is not completed until
after fertilisation. In sharp contrast, mammalian male
meiosis does not start until puberty and is continuous
throughout life.
Introduction
Meiosis consists of one round of deoxyribonucleic acid
(DNA) replication followed by two nuclear divisions. The
two divisions (meiosis I and II) are divided into the same
stages (prophase, metaphase, anaphase and telophase) as
mitosis (Table 1 and Figure 1). The most complex part of
ELS subject area: Cell Biology
How to cite:
Hultén, Maj A (September 2010) Meiosis. In: Encyclopedia of Life
Sciences (ELS). John Wiley & Sons, Ltd: Chichester.
DOI: 10.1002/9780470015902.a0005772.pub2
ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net
Advanced article
Article Contents
. Introduction
. Chromosome Pairing of Homologous Parental
Chromosomes at Meiosis I
. Tools for Identification of Meiosis-specific Chromosome
Structures
. An Integrated Molecular and Cytogenetic Model of the
Crossing-over Process
. Chromosome Segregation
. Consequences of Abnormal Meiosis
Online posting date: 15th September 2010
meiosis occurs during prophase of the first meiotic division
(prophase I). Prophase I is conventionally subdivided into
five stages (leptotene, zygotene, pachytene, diplotene and
diakinesis) that reflect variation in chromosome organisa-
tion and behaviour during this period (Table 1).
Meiosis I has three crucial features that distinguish it
from mitosis: homologous chromosome pairing, reciprocal
recombination (also called crossing-over and chiasma
formation) and importantly a two-step release of sister
chromatid cohesion that allows the segregation of the
homologues on the first meiotic spindle, followed by the
separation of sister chromatids during meiosis II. For ease
of description, these aspects of chromosome behaviour are
presented separately. However, it is important to remem-
ber that they are interdependent events. Thus, the process
of chromosome pairing, reciprocal recombination/cross-
ing-over/chiasma formation are very intimately connected,
and correct segregation of homologous chromosomes at
the first meiotic division can only be accomplished after
successful recombinatorial processes having taken place
beforehand, that is, at meiosis I prophase.
Completion of reciprocal recombination/crossing-over
between parental half chromosomes (chromatids), toge-
ther with sister chromatid cohesion, leads to the formation
of chiasmata. Chiasmata bind homologous chromosomes
physically together to allow the chromosome pair (biva-
lent) to orientate at metaphase I such that the chromosome
movement centres (kinetochores located at the centro-
meres) are facing opposite spindle poles. This mech-
anistically favourable position is of vital importance for
proper kinetochore attachment to opposite spindles, pro-
moting regular chromosome segregation at the subsequent
anaphase I (Figure 1).
It is also important to note the three-dimensional (3D)
configurations of bivalents at metaphase I. This means that
sister chromatids (bound together by cohesin proteins) are
all strictly positioned in the equatorial plate, facilitating
cleavage and transportation of the individual (recombined)
chromosomes to opposite poles, once sister chromatid
cohesion along chromosome arms lapses at the onset of
anaphase I (Figure 1). This type of reductional segregation is
allowed because sister chromatid cohesion is actively
1
 Meiosis

Table 1 Prophase I: stages and landmark events of chromosome behaviour

Stage Description
Leptotene Chromatin condensation begins and the chromosomes first become visible as long, extended thread-
like structures. As part of this condensation process, the chromosomes form a proteinaceous core
(axial element) composed of cohesion proteins and two synaptonemal complex proteins, SYCP2 and
SYCP3. The telomeres (the DNA–protein complexes that cap the ends of all chromosomes) bind to
the nuclear membrane and begin to localise within a limited area of the membrane (‘bouquet’
formation)
Zygotene The transition from leptotene to zygotene is marked by the start of chromosome pairing. The central
core of the synaptonemal complex is formed by the protein SYCP1. Synapsis generally initiates from
chromosome ends. DNA repair proteins, such as RAD51 and DMC1, decorate unpaired axes until
synapsis is complete (see Figure 4)
Pachytene By convention, zygotene ends and pachytene commences at the point when maximal synapsis is
achieved. Intermediate recombination structures mature into crossovers in this stage. The positions of
exchange are marked by foci of the mismatch repair protein MLH1 (see Figure 6)
Diplotene Transition to the diplotene stage is signalled by the lapsing of homologous chromosome pairing, a
process termed desynapsis. Human foetal oocytes arrest in diplotene and remain in this stage until
shortly before ovulation
Diakinesis Desynapsis is complete and the bivalents are held together only at the points of reciprocal
recombination/crossing-over, now visible as chiasmata. The chromosomes continue to condense

protected around the centromeric regions of sister chro-
matids. The orientation of paternal and maternal homo-
logues at the metaphase I plate is random. Therefore,
although each cell produced by meiosis contains only one
of each homologue, the number of possible combinations
of maternal and paternal homologues is 2n, where n is the
haploid number of chromosomes. The random assortment
of homologues at the metaphase I stage produces in
humans 223 (8 388 608) different combinations of chromo-
somes. An additional important mechanism for genetic
diversity in offspring is based on the reciprocal recombin-
ation that has taken place between their grandparental
chromosomes during meiosis in ovaries and testes of their
parents (Figure 1). Bearing in mind that the segregation of
sister chromatids at anaphase II is also random, each child
is expected to be genetically unique.
Chromosome Pairing of Homologous
Parental Chromosomes at Meiosis I
Homologous chromosomes are usually located in separate
regions of the premeiotic nucleus. Chromosomes, there-
fore, need to move actively around the nucleus to search for
and identify their homologous partner. Meiotic chromo-
some pairing takes place at the leptotene and zygotene
stages and is by definition completed at the pachytene
stage. It is generally considered to be a two-phase process
(Figure 2, Figure 3, Figure 4, Figure 5, Figure 6 and Figure 7).
First, homologous chromosomes (or chromosomal seg-
ments) become aligned with chromosome ends attached to
the nuclear membrane. Currently, it is not clear how dis-
tance recognition of homology is achieved to enable this
alignment, although in fungi, animals and plants, there
appears to exist both an early recombination-independent
and DNA double-strand break (DSB)-dependent com-
ponents (Zickler, 2006). It seems possible that in humans
this alignment is mediated by repetitive DNA sequences
such as the so-called minisatellites. Second, after alignment
of homologous chromosomes (or chromosomal segments),
the chromosomes associate intimately in a process termed
synapsis (Figure 4; Barlow et al., 1997). Synapsis is mediated
by a meiosis-specific proteinaceous structure, the synap-
tonemal complex (SC) (review in Page and Hawley, 2004).
There is some evidence that the initial phase of synapsis at
early pachytene is limited to regions of chromosome
homology (homosynapsis), but this restriction may ease
later to allow some non-homologous synapsis (hetero-
synapsis). This change in synaptic behaviour is most easily
identified in cases where there are heterozygosities for
chromosome rearrangements, such as in translocations
and inversions (Figure 3; Saadallah and Hultén, 1986).
Meiotic homologous chromosome pairing and crossover
formation in ovaries of mammals take place during foetal
development (Lyrakou et al., 2002; Perheentupa and
Huhtaniemi, 2009). In contrast, this is a lifelong process
ongoing from puberty in the testes (Perheentupa and
Huhtaniemi, 2009).
Tools for Identification of
Meiosis-specific Chromosome Structures
Chromosome preparations made in the traditional way
(by hypotonic pretreatment and Carnoy fixation) from,
for example, biopsies of mice and human testis allow

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Metaphase I Anaphase I
Telophase II Metaphase II
Figure 1 Chromosome behaviour in the later stages of meiosis. After
diakinesis, the bivalents attach to spindle microtubules and orient in a
monopolar fashion at metaphase I. When orientation is complete, the
cohesin complex proteins that bind sister chromatids are removed (except
at the kinetochores), releasing the chiasmata and allowing the
chromosomes to be pulled to the spindle poles at anaphase I. The
chromosomes reorient on the metaphase II spindle, and the chromatids
separate and move to opposite spindle poles. The net result is the
formation of cells containing a haploid, unreplicated genome. See also
Figure 7a as regards the reciprocal recombination/crossing-over/chiasma
formation taking place at prophase I of meiosis.
identification of numerous sperm-producing cells (sperm-
atocytes) at the meiotic pairing stage of prophase I, as well
as much more rarely cells at the metaphase I and metaphase
II stages. Interestingly, human prophase chromosomes at
the fully synapsed stage (pachytene) show ‘spontaneous’
banding patterns (so-called chromomeres) following block
staining by Giemsa, for example. This banding pattern
corresponds perfectly to the G-banding on mitotic
chromosomes as seen in ordinary lymphocyte preparations
following trypsin treatment and used in clinical cyto-
genetics service laboratories. In 1956, it was discovered that
following surface spreading, electron microscopy (EM)
analysis would allow the detailed visualisation of the dif-
ferent components of this pairing structure, termed the
synaptonemal complex (Moses, 1956). Subsequently, it
was found that immunofluorescence (IF) analysis, apply-
ing various antibodies against proteins identified as com-
ponents of the SC, provided much more detailed
information on the organisation of the SC than that
obtained by EM analysis alone (examples in Figure 4 and
Figure 6). Most researchers have since applied the IF
ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net
Meiosis
Chromatin
LE CE
Kinetochore
(a)
Chromatin
Cohesin
axis
Transverse
fibrils Lateral
(central (axial)
element) element
(b)
(c)
Figure 2 (a) Electron microscopy (EM) image of a single synaptonemal
complex (SC). The tripartite structure of the SC is evident. The structure
comprises two lateral elements (LEs) each of 50 nm and a central region of
100 nm. A thin central element (CE) can be seen within the central region.
(b) Cartoon to show the relationship of the chromatin to the axial cores
formed by the cohesin complex proteins and the LEs of the SC. Two SC
proteins (SYCP2 and SYCP3) are present in the LEs. These are large proteins
that associate with the cohesin complex holding sister chromatids together.
The drawing shows the cohesin constitution of the LE separately, but it is to
be noted that there is no indication that there are in fact two layers making
up the LE. Only one protein, SYCP1, has so far been isolated from the
central region. The C-terminal domain of this protein has been shown to
bind to the chromosomal axes. The central part of the protein is a coiled
coil and stretches out into the central region of the SC. The protein does
not traverse the whole central region but overlaps and associates, at the
N-terminal domain, with SYCP1 fibrils stretching out from the opposite
lateral element. This overlapped region appears to be largely responsible for
the central element. (c) EM of an SC stained to show recombination
nodules (arrows). (a) and (c) courtesy of N. Sadaallah.
technology alone and only a few groups have used both EM
and IF for the analysis of SCs on the same material of testes
or ovaries (Barlow and Hultén, 1997); and there is so far no
report applying all three approaches including prepar-
ations made in the traditional way by hypotonic pretreat-
ment and Carnoy fixation. See also: Chromosomal Bands
and Sequence Features; Karyotype Analysis and Chromo-
some Banding
EM analysis of SCs
The SC was first identified by EM analysis of surface-
spread pachytene spermatocytes, using silver or phospho-
tungstic acid (PTA) staining (Moses, 1956). It appears as a
tripartite ribbon of proteins running along the axes of
3
 Meiosis

(a) (b)

Figure 3 Electron microscopy (EM) pictures of synaptonemal complexes (SCs) at the pachytene stage showing so-called excrescences of unpaired
chromosome segments. (a) Unpaired chromosome segments within inverted segment of chromosome 13 show excrescences. The nucleolar organising
region (NOR) has been broken into two separate parts (N) in the formation of the inversion. (b) Interlocked SC where the unpaired segments show the same
excrescences as the unpaired segments of the XY bivalent, marked X and Y. Only a very small part of the short arms of the X and Y are synapsed. Courtesy of
N. Sadaallah.

Figure 4 Immunofluorescence microscopy (IM) picture of human spermatocyte at the zygotene stage illustrating the RAD51 foci. (a) Labelling with
anti-hRAD51 (white) and sera GS (centromeres, red) show numerous RAD51 foci, some indicated by arrows. (b) Same picture as in (a) but with anti-A1
(anti-lateral element, white) superimposed, illustrating how the RAD51 foci have disappeared along the segments of two bivalents, where synapsis has been
successful, but remain within the interstitial unpaired segment (green and white arrows in (a) and (b) and white arrow in insert). Reproduced from Barlow
et al. (1997), with permission from Nature Publishing Group.

paired chromosomes (Figure 2). Any unpaired segments
show so-called excrescences (Figure 3; Saadallah and
Hultén, 1986), indicative of aggregation of proteins that
would disappear following synapsis, including the histone
2 variant AX (gH2AX), the radiation sensitive 51 (RAD51)
and the disrupted meiotic cDNA 1 (DMC1) proteins. SC
lengths at pachytene vary considerably between human
sperm-producing (spermatocyte) and egg-producing
(oocyte) cells: in spermatocytes, the total length per cell is
approximately 260 mm, whereas in oocytes, it exceeds

4 ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net
 Meiosis

5 3
3 5
3 5
5 3
SPO11
Double-strand break

MRE11/RAD50/NBS1
Strand resection

RPA, RAD51, DMC-1

Single end invasion

Second end capture

MSH4/MSH5

Double Holliday
junction

MLH3/MLH1, GEN1

Crossover
formation

Figure 5 Double-strand break (DSB) model of recombination (see Kirkpatrick, 1999). Cutting of strands in opposite orientation at each junction
(arrowhead) produces a crossover.

520 mm (Wallace and Hultén, 1985; Tease and Hultén,
2004). In both sexes, a limited part of each chromosome is
associated with the SC and, therefore, in intimate contact
with the homologous regions on its partner chromosome.
Most of the chromosome is instead present as chromatin
loops surrounding the SC and is not involved in the
complex interactions between two parental chromatids,
leading up to reciprocal recombination/crossing-over/chi-
asma formation. However, recombination is thought to be
initiated by the formation of DSBs in the DNA loops. Then
these breaks are brought to the chromosome axis where
they are further processed to allow meiotic recombination.
As far as is known, there are no specific DNA sequences
localised within the central region of the SC, but this DNA
tends to be more AT (adenosine, thymidine) rich than the
genome at large.
Electron microscope investigations also identified small
structures, termed recombination nodules, associated with
SC formation. These nodules are categorised as early
recombination nodules (ENs), transformed nodules (TNs)
or late recombination nodules (LNs) (Moens et al., 2007).
This discrimination is based on the time of appearance of
the recombination nodules and presumptions regarding
function. ENs are associated with synapsing chromosomal
axes. They are generally small and ellipsoid and are
assumed to be involved in homology testing between
aligned chromosomal segments. TNs are formed from ENs
through the acquisition of various DNA repair proteins.
These nodules are associated with SC extension as part of
the progression of synapsis. LNs are present following
synapsis (Figure 2c; Saadallah and Hultén, 1986). They can
vary in appearance from round structures to bar-like

ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net 5
 Meiosis
(a)
(b)
(c)
Figure 6 Detecting the positions of crossovers at pachytene using the
DNA mismatch repair protein, MLH1. The cells have been stained using
antibodies against SYCP3 (red), MLH1 (yellow) and, in the spermatocyte,
the kinetochore (blue). (a) Normal pachytene spermatocyte. (b) Normal
pachytene oocyte. There are obvious differences between the spermatocyte
and the oocyte: the SCs are much longer in the oocyte; there are more
MLH1 foci in the oocyte; MLH1 foci tend to be positioned closer to the
telomeres in the spermatocyte. (c) Pachytene oocyte showing failure of
pairing affecting some chromosomes (arrows). MLH1 foci are present on
synapsed chromosome pairs (arrowheads).
6 ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net
objects straddling the SC and are believed to be involved
in the final part of the sequence of events leading up to
reciprocal recombination. ENs occur in larger numbers
than LNs, typically at least an order of magnitude higher. It
is generally held that LNs evolve from a subset of ENs.
Immunofluorescence analysis of the
structural components of the SC
The first meiotic proteins visualised are the components of
the cohesin complex, which holds sister chromatids toge-
ther, that is the structural maintenance of chromosome 1b
(SMC1b), the recombination 8 (REC8) and the stromaline
3 (STAG3) proteins (Prieto et al., 2004). The proteins
appear as punctuated foci in preleptotene cells. During
leptotene, these signals organise into fibrillar patterns and
proteins that make up the SC appear. The cohesins attach
to the chromatin and become sandwiched within the axial
elements and the proteins forming the remaining part of the
SC scaffold (Figure 2). Three major SC proteins that form
the basis for the SC structure have been identified to date
(Table 2). Two of these, SYCP2 (synaptonemal complex
protein 2) and SYCP3 are located at the axes of chromo-
somes as they condense during early prophase I, forming
the axial/lateral elements of the SC. SYCP2 and SYCP3
appear to associate with (or are loaded on to) the cohesin
protein complex that binds together sister chromatids fol-
lowing DNA replication (Figure 2b). The third protein,
SYCP1, is present in the central region of the SC. SYCP1 is
a long filamentous protein. Its C-terminal end binds to the
lateral element, with the N-terminal region pointing into
the central region. N-terminal regions from opposite lateral
elements associate centrally to hold the SC together (Figure
2b). More recently, other components of the central elem-
ent have been identified in mammals: SC central element
(SYCE) 1 and 2 plus FKBP6 (FK506 binding protein 6).
Immunofluorescence analysis of XY
behaviour at prophase I
IF analysis has allowed detailed information to be obtained
on the behaviour of aspects of specialised meiotic
chromosome pairing. For example, in human spermato-
cytes, the heteromorphic sex chromosomes undergo a
different schedule of synapsis from the autosomes (Arm-
strong et al., 1994). This pattern of behaviour may be
predicated on the need to maintain the X in a genetically
inactive state during meiosis. The X- and Y-chromosomes
share a relatively small region of homology (approximately
2.6 Mb in length) at the distal ends of their short arms (the
‘pseudoautosomal’ region, PAR). They also have a much
smaller (approximately 0.23 Mb) PAR of homology at the
ends of the long arms. Synapsis initiates at the short-arm
PAR in early pachytene and goes beyond the region of
homology occasionally to include the entire short arm.
However, this heterosynapsis is not long lasting and the
chromosomes begin to separate (desynapse). By mid-
pachytene, the chromosomes are associated only at their
 Meiosis

x x 1

3
XY
(a) (b)

(c) (d)

Figure 7 (a) Cartoon illustrating how the configurations in (b) are achieved by bivalents with one or two chiasmata. Two chromosome pairs are shown, in
each case one homologue is coloured blue, the other red. A reciprocal recombination/crossover between a blue and a red chromatid generates an exchange
that is visible as a cross-configuration/chiasma in the metaphase I bivalent. The acrocentric chromosome pair has a single reciprocal recombination/
crossover/chiasma and produces a rod bivalent at metaphase I; the metacentric has two reciprocal recombinations/crossovers/chiasmata and produces a ring
bivalent. (b) Metaphase I spermatocyte. Pairs of homologous chromosomes are held together by variable numbers of chiasmata. Bivalents with 1, 2 or 3
chiasmata are indicated, as is the XY-chromosome pair. (c) Metaphase II spermatocyte. The chromatids of each chromosome (arrowheads) are held together
only at the centromeres (arrow). (d) Metaphase I spermatocyte from a man with an abnormally low number of chiasmata. In contrast to (b), bivalents
(arrows) have only one or two chiasmata; additionally, a number of chromosome pairs have failed to form crossovers and are present as univalents
(arrowheads).

Table 2 Major components of the mammalian synaptonemal complex and cohesin complex
Axial/lateral element Transverse filament Central element Cohesin core
SYCP2 SYCP1 TEX12 STAG3
SYCP3 SYCE1 SMC1b
SYCE2 REC8

very distal tips of their short arms. In approximately half of
early pachytene cells, the regions of homology of the long
arms also associate. The sex chromosomes undergo con-
siderable morphological changes during pachytene, even-
tually forming a highly differentiated condensed ‘sex
vesicle’ in late pachytene. This unusual pattern of synapsis
and chromosome differentiation provides a reliable means
to subdivide pachytene in the human male, and thereby can
be exploited to distinguish early to late pachytene cells
when examining meiotic behaviour of autosomes. The
X-chromosome pair in human prophase I oocytes does not
show any difference in behaviour from the autosomes.
An Integrated Molecular and
Cytogenetic Model of the
Crossing-over Process
The currently accepted molecular model of crossing-over
is the DSB repair (DSBR) model (Kirkpatrick, 1999).The
DSBR pathway relies on double Holliday junction (dHJ)
formation and resolution to produce crossovers (Figure 5).
This includes DNA breaks initiated at an early stage of
meiosis (leptotene) followed by reciprocal recombination
between parental chromatids, which is completed during

ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net 7
 Meiosis
Table 3 Timing and possible functions of some DNA repair proteins that associate with chromosome cores during leptotene,
zygotene and pachytene stages of prophase I
Protein Stages present
SPO11 (sporulation) Leptotene to zygotene
RAD51 Leptotene to pachytene
DMC1 (disrupted meiotic cDNA) Leptotene to pachytene
RPA (replication protein A) Zygotene to pachytene
BLM (Bloom syndrome mutated Leptotene to pachytene
helicase)
MSH 4/5 (MutS homologue) Zygotene to pachytene
MLH1 (MutL homologue) Zygotene to diplotene
MLH3 Pachytene
GEN1 Pachytene
the following zygotene and pachytene stages (Table 1). This
model is primarily based on experiments in bacteria and
yeast, but is likely to be equally relevant to higher organ-
isms, including humans (Sung and Klein, 2006; West,
2009). An expanding array of DNA repair proteins have
been identified as playing a role in the recombination
process of crossing-over (Table 3).
SPO11 induces double-strand breaks at the
leptotene stage
DSBs appear to be an essential prerequisite to homology
testing between parental chromosomes, which involves the
initial stages of recombination between closely aligned but
not yet synapsed chromosomes. Synapsis thus requires the
formation of DSBs in the chromatin through the action of
the topoisomerase II-related protein SPO11 (sporulation
gene 11) during leptotene. An endonuclease then nicks the
DNA close to the DSB liberating SPO11 attached to a short
oligo nucleotide (Keeney and Neale, 2006). By this action,
the first bases of single-stranded DNA (ssDNA) overhangs
are formed. They are extended by a combination of activ-
ities involving exonucleases and helicases.
Numerous DSBs are formed at leptotene and it is widely
accepted that the appearance of g-H2AX, a variant histone
phosphorylated at serine 139, is a suitable marker for their
presence (Redon et al., 2002). Foci of g-H2AX can be
detected by immuno-cytohistochemistry. These foci dis-
appear following synapsis but remain visible along the
length of any unpaired lateral element (including the
unpaired parts of the XY bivalent). The g-H2AX foci are
8 ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net
Role
Produces DSBs, essential for synapsis
RecA homologue that binds to
single-stranded DNA; possible role in
early steps of recombination by
mediating single end invasion
RecA homologue that binds to
single-stranded DNA; colocalises
with Rad51
Binds to single-stranded DNA,
possibly involved in early steps of
recombination
Helicase, colocalises with RPA,
possibly functions in recombination
Required for chromosome pairing; in
yeast, interacts with MLH1 to control
crossing-over
Required for crossing-over
Involved in DNA mismatch repair
Required for resolving of Holliday
junctions
thus likely constituents of the excrescences of unpaired
lateral elements of the SC seen by EM (Figure 3; Saadallah
and Hultén, 1986). The majority of these DSBs will not go
on to become involved in crossing-over; instead, the
invading strand is displaced and reanneals with the other
side of the DSB. This is known as synthesis-dependent
strand annealing and can produce gene conversion events,
involving transition of DNA nucleotides between maternal
and paternal chromosomes. It is likely that the numerous
DSBs constitute sites of potential crossovers reflected as
the type of hotspots described by the model proposed by
sperm experimentation. This model implies that there are
so-called crossover hotspots of around 1–2 kb with inter-
vals of lower recombination frequency within the adjacent
90–125 kb (review in Kauppi et al., 2009; Hastings et al.,
2009; Stankiewics and Lupski, 2010). It is important to
note, however, that only a small proportion of these will be
selected for crossover formation, as described in the fol-
lowing text.
MRE11 is required for recombination
initiation
In addition to SPO11, a number of other proteins are
required for DSB formation and recombination initiation.
The best studied of these accessory proteins are the MRX
and MRN complexes. The MRN complex, composed of
the meiotic recombination 11 (MRE11), the RAD50 and
the Nijmegem breakage syndrome 1 (NBS1) proteins
localises to sites of DNA damage where it plays a role in
genome maintenance (Rupnik et al., 2010). MRE11 has

multiple functions including 3’ to 5’ double-strand (ds) and
single-strand (ss) DNA exonuclease and ssDNA endonu-
clease activities (Borde, 2007); RAD50 contains Zn2+-
binding hooks that allow dimerisation, and the formation
of a flexible bridge that can cross a DSB gap or link sister
chromatids together. Combined with MRE11 and NBS1
dimers, the complex can be tethered to DNA.
During meiosis, the MRX complex is required for
SPO11-mediated DSB formation. The MRN complex is
also believed to be involved in recombination initiation,
specifically 5’ to 3’ exonucleolytic resection. The exact
mechanism for this is unknown but it has been suggested
that the MRN complex recruits and controls other exo-
nuclease activity. These exonucleases degrade the ends of
the DSB to produce ssDNA overhangs.
RAD51 and DMC1 promote DNA strand
invasion
Following strand resection, the ssDNA overhangs are then
available for binding by RAD51 and DMC1, which pro-
mote strand invasion of a chromatid from the homologous
chromosome (Figure 4; Barlow et al., 1997; Keeney and
Neale, 2006). Stable, homologous strand invasion dis-
places the homologous strand to form a displacement loop,
which is subsequently available for capture by the invading
homologue thus forming a mature dHJ. The RAD51/
DMC1 recombinases thus promote reciprocal strand
exchange between parental chromatids and lead to intim-
ate pairing and synapsis of the lateral elements of the SC.
This zipping-up process of homologous chromosomes at
the zygotene stage most often starts near the ends of
chromosomes and progresses towards the middle. In some
organisms, recombination sites fated to become crossovers
are thought to act as sites of synaptonemal complex (SC)
initiation (Lynn et al., 2007). When full synapsis is
achieved, the pachytene stage has been reached.
Studies have indicated that RAD51 and DMC1 are
components of ENs as identified by EM analysis (Moens
et al., 2007). RAD51 and DMC1 are homologues of the
bacterial RecA (recombinational DNA repair gene A)
protein, which is involved in homologous recombination
and repair of DNA damage. IF analysis has illustrated how
RAD51 is initially deposited as discrete foci on one or other
of the unsynapsed lateral elements of the SC. These foci
disappear once synapsis is established but remain in any
unsynapsed regions (including the unsynapsed regions of
XY) and are likely to represent parts of the SC excrescences
seen by EM (Figure 3; Saadallah and Hultén, 1986).
Apparently, the appearance and disappearance of RAD51
is a rapid process as the RAD51 foci can be seen to have
come and gone within the same synapsing bivalent during
zygotene (Figure 4; Barlow et al., 1997).
In most organisms studied in this respect, the number of
DNA DSBs is much greater than the observed number of
crossovers. Thus, many initial recombination events are
not resolved as a crossover. Equally, most of the RAD51/
DMC1-containing ENs are not involved in reciprocal
ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net
Meiosis
recombination as part of the ongoing crossover and chiasma
formation process. A subset (approximately 50 in human
males, 70 in human females) is resolved as crossovers while
the remainder is resolved as gene conversion events, thus
contributing to the genetic diversity in offspring. See also:
Genetic Mapping: Comparison of Direct and Indirect
Approaches; Genetic Maps: Direct Meiotic Analysis
Digestion and unwinding DNA by a number
of additional proteins
Following on from the formation of a displacement loop,
the joined DNA molecules must be arranged and held in
the correct conformation for dHJ formation. It is believed
that the components of the TNs, identified by EM analysis
of the SC, are responsible for this although the exact
mechanism of action is unknown. These proteins include
endonucleases for digesting DNA and also helicases such
as BLM (Bloom Syndrome) for unwinding DNA. BLM is
of particular importance as the C-terminal domain can
interact with a number of proteins, including MLH1 (mutL
homologue 1), which may represent a method for recom-
bination nodule progression towards finalising the cross-
over process (see later discussion).
Other components of the TNs have been confirmed as
RPA (replication protein A), MSH4 (mutS homologue 4)
plus various topoisomerases. RPA is a heterotrimeric
protein complex, which can bind to ssDNA. RPA associ-
ates with chromosome cores of synapsing homologues and
overlaps with RAD51 in timing of appearance. BLM is a
DNA helicase that is capable of unzipping dsDNA. All
eukaryotes studied so far also encode homologues of the
baterial mismatch repair (MMR) proteins, MutL and
MutS (methyl-directed mismatch repair proteins). The two
meiosis-specific MutS homologues MSH4 and MSH5
function together as a heterodimer to facilitate the for-
mation of reciprocal recombination/crossing-over/chi-
asmata formation. The MSH4–MSH5 dimer is not
involved in MMR but is believed to function as a sliding
clamp capable of stabilising Holliday junctions.
Finalising the crossing-over process by the
action of MLH3/MLH1 and GEN1
There are also several MutL homologues in eukaryotes.
The DNA MMR protein MLH1 and the meiosis-specific
MLH3 have been shown to be present in the LNs as rec-
ognised by EM, marking foci of crossovers (Figure 2; see
also Saadallah and Hultén, 1986). Therefore, the selected
sites of crossover formation can be identified at pachytene
by IF staining for the presence of the DNA MMR proteins,
MLH1 and MLH3. The presence of MLH1 as discrete foci
along the SC in human spermatocytes and oocytes is
illustrated in Figure 6. These foci mimic the numbers and
distributions of reciprocal recombination sites and chi-
asmata (see later discussion). Recently, another protein,
GEN1, functioning in resolving the Holliday junctions has
9
 Meiosis
(a) (b)
Figure 8 Human spermatocyte at the metaphase I stages (a) and (b), where the chiasmata have been highlighted (middle) and oocyte at the metaphase I
stage, revised from Yuncken (1968). Note the difficulty in identifying the chiasmata in the oocyte in comparison to the spermatocyte. (a) Reproduced from
Hultén et al. (1970), with permission and (b) from Yuncken (1968), with permission from S. Kargel AG, Basel.
been discovered (review in West, 2009). See also: Mismatch
Repair Genes
Chiasma(ta)
The position of crossover events becomes cytogenetically
apparent as a bivalent condenses during diplotene and
diakinesis (Figure 7a and Figure 8). Sister chromatids remain
tightly associated (due to the sister chromatid cohesion
complex) proximally and distally to the crossover giving
rise to a cytogenetically visible structure called chiasma
(plural chiasmata). Chiasma numbers and positions can be
analysed in metaphase I spermatocytes (Figure 7b). Chi-
asmata provide a reliable means of determining the rate of
crossing-over at both the genomic and the chromosomal
levels in the human male (Laurie and Hultén, 1985; Hultén,
1994). See also: Genetic Maps: Direct Meiotic Analysis
Unfortunately, this type of analysis has so far not been
possible in human females (Figure 8). Female meiosis arrests
at the diplotene stage in foetal ovaries, at which time
chromosomes are long and slender, and it is exceedingly
difficult to differentiate twists from chiasmata at this stage.
Metaphase I takes place just before ovulation, usually
within a single oocyte at a time. This scarcity of material for
study has precluded the direct approach for studying pat-
terns of meiotic reciprocal recombination and crossing-
over in human females by analysis of chiasmata at the
metaphase I stage. However, these types of studies have
been performed in mice, using hormone stimulation and
in vitro culture of oocytes (Hultén et al., 1995; Lawrie et al.,
1995). See also: Genetic Mapping: Comparison of Direct
and Indirect Approaches; Genetic Maps: Direct Meiotic
Analysis
Crossovers are non-randomly distributed with regard to
both numbers per chromosome pair and positions along
chromosome arms. Each bivalent receives at least one
exchange (the so-called obligate crossover). Additional
crossovers (up to four or five per bivalent) are more likely the
longer the individual bivalents are at the stage when crossing-
over is finalised, that is, the pachytene stage. The positions of
10 ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net
XY
crossovers along chromosome arms reflect at least two fac-
tors: preferential formation in certain chromosomal seg-
ments and positive crossover interference, a process by which
the presence of a crossover reduces the probability of a sec-
ond crossover being formed nearby. The former is exempli-
fied by the high rate of chiasma formation close to
chromosome ends in human spermatocytes (Figure 6a and
Figure 7b). The influence of interference is most easily seen
when two or more chiasmata are present along a chromo-
some arm. Adjacent chiasmata rarely form close to one
another but are more usually separated by a comparatively
large chromosome length. Currently, the mechanism of
interference is unclear (review in Stahl and Housworth,
2009; Martinez-Perez and Colaiacovo, 2009).
A third factor that affects the number and position of
crossovers is the presence of mechanisms that favour the
repair of DNA DSBs as non-crossover events. For
example, mice and yeast mutants lacking the BLM helicase
display an increased number of chiasmata between hom-
ologous chromosomes (Holloway et al., 2010).
Sex differences in frequency and position of
crossing-over/chiasmata
Human males with normal fertility show remarkably little
interindividual variation in numbers of chiasmata, with an
average of approximately 50 per spermatocyte (range 43–60
per cell) (Hultén, 1974; Laurie and Hultén, 1985). Analysis of
MLH1 foci at pachytene has produced a similar estimate of
crossover frequency in spermatocytes (Barlow and Hultén,
1998; Lynn et al., 2002; Sun et al., 2004; Martin, 2008).
Numbers of crossovers, as estimated from MLH1 foci, is
higher in oocytes prepared from foetal ovaries. Initial MLH1
analysis has suggested an average of approximately 70
crossovers per oocyte at pachytene, with a larger intercell
variability (range 40–100) than in spermatocytes (Barlow
and Hultén, 1998). Subsequent studies have confirmed the
occurrence of a large variation in crossover frequency
between individual oocytes (Tease et al., 2002; Lenzi et al.,

2005; Cheng et al., 2009). It is likely that some of this variation
is due to underestimation of the crossover frequency when
counting MLH1 foci due to the temporary nature of their
appearance. The higher rate of recombination in oocytes is
most probably related to the considerable difference in
pachytene chromosome length described earlier (Tease et al.,
2006). The female genome has a longer physical platform for
establishment of reciprocal recombination/crossing-over/
chiasmata than the male. Not only do the two sexes show a
significant variation in recombination frequency, but they
also display differences in distribution (Tease et al., 2002). In
spermatocytes, the MLH1 foci/chiasmata are often located
very close to the ends of the chromosomal axes. In oocytes,
MLH1 foci are located more interstitially (away from
chromosome ends) and only very rarely positioned so near to
telomeric segments as in spermatocytes (compare Figure 6a
and b). Indirect family linkage analyses, tracing DNA
markers between generations, have similarly identified this
intersex variation in numbers and distributions of cross-
overs (Lynn et al., 2004). See also: Genetic Mapping:
Comparison of Direct and Indirect Approaches; Genetic
Maps: Direct Meiotic Analysis
Chromosome Segregation
At metaphase I, the pairs of homologous chromosomes
(bivalents) attach to spindle microtubules and move to the
spindle equator in preparation for nuclear division. At the
first meiotic division, sister kinetochores (microtubule-
attaching segments of the centromeres) act as a single unit
and orient in a monopolar fashion (both attached to the same
pole of microtubules). This is due to the fact that sister
chromatid cohesion is actively protected around centromeric
regions during meiosis I, which is quite distinct from mitosis
where the kinetochores of sister chromatids orient to
opposite spindle poles. See also: Chromosomes during Cell
Division; Kinetochore: Structure, Function and Evolution;
Mitosis: Chromosome Segregation and Stability
The chiasmata in each bivalent act as anchors to hold the
pairs of homologues together during the orientation pro-
cess within the equatorial plate of metaphase I cells. Evi-
dence from experimental organisms shows that incorrect
orientation, or failure to attach to spindle microtubules,
can switch on a signalling pathway that results in cell div-
ision arrest until the chromosomes successfully interact
with the spindle (Nicklas, 1997). It is presumed that a
similar mechanism exists in human spermatocytes. There is
some doubt as to whether it is as sensitive (or possibly even
present) in human oocytes.
The cohesin protein complex is present at the kine-
tochore of meiotic chromosomes (Suja and Barbero, 2009).
Three meiosis-specific variants of cohesin components
have been identified: STAG3, SMC1b and REC8 (Table 2).
Sister chromatid cohesion is released from chromosomes
by the action of the separase enzyme, ESP1 (extra spindle
pole bodies 1), at the metaphase to anaphase I transition.
Centromeric cohesion is protected by the Shugoshin (SGO)
ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net
Meiosis
family of proteins until anaphase II, at which time REC8 is
cleaved by separase. The presence and retention of cohesin
proteins is crucial for monopolar orientation of sister
kinetochores (both attached to the same pole) at metaphase
I and the remaining centromeric cohesion allows the
chromatids to align at metaphase II.
A programmed lapse of sister chromatid cohesin along
chromosomal arms results in the loss of the crossover
associations holding the homologous chromosomes toge-
ther. The homologues are then able to move to opposite
spindle poles as the microtubules shorten. The resulting
daughter nuclei, therefore, obtain half of the chromosome
complement (Figure 7c). It is important to note that
maternally and paternally inherited homologues assort at
random at anaphase I. The resulting daughter cells,
therefore, contain a haploid chromosome set different from
that contributed by maternal and paternal germ cells. It is
also important to remember that the chromatids of each
chromosome are now no longer identical because of
reciprocal recombination (see Figure 1). These two pro-
cesses of random assortment and meiotic recombination
contribute to genetic variation in offspring.
In oocytes, the cytoplasmic division at anaphase I, tak-
ing place before ovulation, is highly unequal, producing a
large secondary oocyte and a residual, minute cell termed
the first polar body. The polar body ceases meiosis and
the chromosomes begin to degenerate. Oocytes arrest at
metaphase II and are ovulated at this stage. They are
stimulated to complete meiosis only after fertilisation. In
spermatocytes, the products of the first meiotic division are
equal in size and both go on to complete meiosis II.
Chromosome condensation resumes very shortly after
anaphase I, and the chromosomes soon orient on the
metaphase II spindle. During the second meiotic division,
the release of cohesion along all chromosomal regions
allows the segregation of the sister chromatids. Although
this second meiotic division has much in common with a
mitotic division, the daughter nuclei that are produced are
not identical – due to reciprocal recombination at prophase
I and due to the random orientation and assortment of
bivalents at anaphase I.
Once chromosome orientation is complete (and following
fertilisation in the case of oocytes), centromere cohesion lapses
and the spindle microtubules pull each chromatid to the poles
at anaphase II. Meiosis is now complete. The resulting cells
in male meiosis are termed spermatids. They undergo very
considerable morphological changes in the process of forming
spermatozoa (spermiogenesis). In female meiosis, cytoplasmic
division at anaphase II is again very unequal producing a
second small polar body. The egg nucleus decondenses to
form the female pronucleus of the zygote. See also: Mitosis:
Chromosome Segregation and Stability
Consequences of Abnormal Meiosis
Meiosis is a surprisingly error-prone process in humans
and thereby has a significant adverse impact on human
11
 Meiosis
reproduction (review in Hultén et al., 2010a). Meiotic
errors can result in infertility and are also responsible for
generating the genetically imbalanced gametes that pro-
duce aneuploid conceptions. Errors of meiotic chromo-
some behaviour are the single largest contributor to
genetically determined congenital abnormalities and
mental impairment affecting live-born children.
Chromosome pairing and recombination
errors
All aspects of meiotic chromosome behaviour are error
prone. For example, over 30% of human pachytene
oocytes may show some form of chromosome pairing
anomaly (Tease et al., 2006). Commonly, homologous
chromosomes fail to pair, a phenomenon termed asynapsis
(Figure 6c). In yeast, anomalies of chromosome pairing can
trigger cell checkpoints resulting in arrest of cell develop-
ment and ultimately cell death. It seems likely a similar
phenomenon occurs in human germ cells. If this mech-
anism is present, then any increase in the already high
proportion of foetal oocytes with pairing errors could
result in depletion of the germ cell population and lead to
the premature onset of menopause in women. Similarly,
meiotic pairing errors in spermatocytes could result in an
insufficiency of sperm production in men. A reduction in
germ cell population would be far more detrimental in
human females because they produce just 300–400 mature
oocytes in a lifetime compared with 300–400 million sperm
produced daily in human males.
Incorrect alignment (unequal synapsis) of homologues
in conjunction with reciprocal recombination/crossing-
over may generate a large variety of deletions and dupli-
cations that can cause genetic disease in offspring. It should
be noted, however, that some of this type of non-homolo-
gous recombination (NAHR) is also thought to contribute
to the large amount of DNA copy number variation (CNV)
that is now known to exist in the normal population (review
in Hastings et al., 2009; Sharp, 2009; Stankiewics and
Lupski, 2010).
Failure of crossing-over in fully synapsed chromosome
pairs results in the presence of unpaired chromosomes
(univalents) at metaphase I (Figure 7d). This phenomenon is
termed desynapsis. The lack of a chiasmate association
means that homologous chromosomes may segregate at
random with respect to one another, with a resulting
marked increase in the rate of aneuploid gametes, which are
imbalanced as regards chromosome copy numbers. Any
unpaired chromosomes at metaphase I may undergo a so-
called predivision, that is, chromatids separate (as in
mitosis) leading to extra and missing chromatids in
daughter cells (see Hultén et al., 2008, 2010b).
In spermatocytes, there is evidence that failure of
crossing-over can result in the developmental arrest of the
cells at early prophase and at metaphase I; these cells may
then be lost through either necrotic or apoptotic pathways.
Investigation of testicular biopsies from men attending
infertility clinics have shown an increased likelihood of
12 ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net
meiotic errors such as a significantly reduced number of
MLH1 foci at the pachytene stage of prophase I or chiasma
frequency at metaphase I (Hultén et al., 1970; review in
Martin, 2008).
Non-disjunction
Chromosome abnormalities occur at a much higher level in
humans than in any other species. More than 50–60% of
clinically recognised pregnancies have some form of
chromosome abnormality (Vanneste et al., 2009; Hultén
et al., 2010a). Monosomies and most trisomies are nor-
mally eliminated early in gestation because they are gen-
erally incompatible with normal development. Sex
chromosome monosomy (45, X) is the only monosomic
condition that may proceed to term. The consequences of
trisomy are less severe for the sex chromosomes compared
with the autosomes, and therefore, these are more common
among live births.
Analyses of the chromosome complements of sperm-
atozoa have shown that malsegregation (non-disjunction)
of chromosomes is normally uncommon (review in Martin,
2008). Current estimates indicate a rate of approximately
2% aneuploid spermatozoa. Paternal non-disjunction only
accounts for approximately 10% of all autosomal trisomies
but certain autosomal trisomies (e.g. 2 and 8) have an
increased incidence of paternally derived cases. Paternal
errors contribute more frequently to sex chromosome
aneuploidy and account for approximately 10% of 47,
XXX females; 50% of 47, XXY; all 47, XYY males and
80% of 45, X females. Recent studies have indicated that
infertile men attending reproductive clinics for collection of
sperm for intracytoplasmic sperm injection (ICSI) tend to
have increased rates of aneuploidy in their sperm.
The rate of aneuploid sperm is elevated in men carrying
structural chromosome rearrangements. For example, in
men with reciprocal translocations, the proportion of gen-
etically imbalanced sperm may reach 60–70%. Homolo-
gous chromosome synapsis involving all four chromatids
leads to a quadrivalent at metaphase I. The proportion of
chromosomally unbalanced sperm generated is dependent
on the way the quadrivalent segregates at anaphase I.
Commonly a chiasma is in an unusual position, between the
centromere and the break point (the interstitial segment).
Even the most normal (alternate) segregation pattern (where
the normal and translocated chromosomes segregate to
opposite poles) will then give rise to unbalanced sperm. It
should in this context be noted that this complication means
that it is not possible from the proportion of sperm with
normal, balanced and unbalanced chromosomes to differ-
entiate between alternate anaphase I segregation with a
chiasma in the interstitial segment and adjacent segregation
without a chiasma in this particular position (Goldman and
Hultén, 1993; Armstrong and Hultén, 1998).
Human oocytes have a higher predisposition for
chromosome segregation errors than spermatocytes. Over
90% of conceptions with autosomal aneuploidy such as
trisomy 21 associated with Down syndrome are the result

of chromosome non-disjunction in oocytes. Indirect gen-
etic analysis has indicated that abnormal patterns of
crossover distribution, that is, failure of crossing-over or
formation of exchanges very close to the centromere or
telomere, may increase the risk of chromosome non-dis-
junction in oocytes. It is not yet clear why, for some
chromosome pairs, bivalents with particular chiasma dis-
tributions should be at increased risk of malsegregation.
The only factor that is known unequivocally to influence
the rate of non-disjunction is maternal age. Although many
hypotheses have been advanced to explain the increased
risk on chromosome segregation errors with age, it is fair to
say that our understanding of this phenomenon remains
very incomplete. One possibility is the accumulation of pre-
existing trisomy 21 oocytes during development from
foetal life to adulthood (Hultén et al., 2008, 2010b). We
have documented that trisomy 21 mosaicism is common in
foetal ovaries, obtained from termination of pregnancy for
a non-medical/social reason (Hultén et al., 2008). We have
further suggested that contrary to current dogma, the
maternal age effect is due to obligatory, secondary, non-
disjunction of trisomy 21 oocytes that have accumulated
during development, involving a reduction in numbers
from a prenatal maximum of 7 million to the 300–400
selected for maturation to ovulation in adulthood (Hultén
et al., 2010b). See also: Meiosis and Mitosis: Molecular
Control of Chromosome Separation
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Further Reading
Alsheimer M (2009) The dance floor of meiosis: evolutionary
conservation of nuclear envelope attachment and dynamics of
meiotic telomeres. Genome Dynamics 5: 81–93.
de Boer E, Lhuissier FG and Heyting C (2009) Cytological
analysis of interference in mouse meiosis. Methods in Molecular
Biology 558: 355–382.
Burgoyne PS, Mahadevaiah SK and Turner JM (2009) The
consequences of asynapsis for mammalian meiosis. Nature
Reviews. Genetics 10(3): 207–216.
Handel MA and Schimenti JC (2010) Genetics of mammalian
meiosis: regulation, dynamics and impact on fertility. Nature
Reviews of Genetics 11: 124–136.
Harrison CJ, Alvey E and Henderson IR (2010) Meiosis in
flowering plants and other green organisms. Journal of
Experimental Botany 61: 2863–2875.
Inagaki A, Schoenmakers S and Baarends WM (2010) DNA
double strand break repair, chromosome synapsis and
transcriptional silencing in meiosis. Epigenetics 5: 255–266.
Khil PP and Camerini Otero RD (2009) Variation in patterns of
human meiotic recombination. Genome Dynamics 5: 117–127.
Neale MJ and Keeney S (2006) Clarifying the mechanics of
DNA strand exchange in meiotic recombination. Nature 442:
153–158.
Sasaki M, Lange J and Keeney S (2010) Genome destabilization
by homologous recombination in the germ line. Nature Reviews
in Molecular Cell Biology 11: 182–195.
Sherthan H (2009) Analysis of telomere dynamics in mouse
spermatogenesis. Methods in Molecular Biology 558: 383–399.
Susiarjo M, Rubio C and Hunt P (2009) Analyzing mammalian
female meiosis. Methods in Molecular Biology 558: 339–335.
Yang F and Wang PJ (2009) The mammalian synaptonemal
complex: a scaffold and beyond. Genome Dynamics 5: 69–80.
Yin S, Sun XF, Schatten H and Sun QY (2008) Molecular insights
into mechanisms regulating faithful chromosome separation in
female meiosis. Cell Cycle 7(19): 2997–3005.