Crossing Over Prevents Homologous Chromosomes From Separating During Meiosis I

How is the same process responsible for genetic recombination and multifariousness as well the cause of aneuploidy? Agreement the steps of meiosis is essential to learning how errors occur.

Organisms that reproduce sexually are idea to have an advantage over organisms that reproduce asexually, because novel combinations of
are possible in each generation. Furthermore, with few exceptions, each individual in a
of sexually reproducing organisms has a distinct genetic limerick. We have
to thank for this diverseness.

Meiosis, from the Greek word
meioun, meaning “to make minor,” refers to the specialized procedure by which germ cells divide to produce
gametes. Because the
number of a
remains the aforementioned from i generation to the next, the chromosome number of germ cells must be reduced by half during meiosis. To accomplish this feat, meiosis, unlike
mitosis, involves a single circular of
Deoxyribonucleic acid
followed past ii rounds of
division (Figure 1). Meiosis too differs from mitosis in that it involves a process known as
recombination, during which chromosomes exchange segments with one another. Every bit a effect, the gametes produced during meiosis are genetically unique.

Researchers’ initial understanding of meiosis was based upon conscientious observations of chromosome behavior using light microscopes. Then, in the 1950s, electron microscopy provided scientists with a glimpse of the intricate structures formed when chromosomes recombine. More recently, researchers have been able to identify some of the molecular players in meiosis from biochemical analyses of meiotic chromosomes and from genetic studies of meiosis-specific mutants.

Meiosis Is a Highly Regulated Process

A schematic diagram shows key events in mitosis and meiosis during the development cycles of male and female sex cells in humans. During fetal development, cells undergo a period of mitotic proliferation. In females, the cells enter meiosis, followed by meiotic arrest. Cells exit meiotic arrest and are either lost before birth or undergo follicle formation after birth. After puberty, these cells are either ovulated each month, one at a time, or becomes atretic. During fetal development in males, proliferating cells enter mitotic arrest. After birth, they enter a second period of mitotic proliferation. After puberty, the cells undergo meiotic divisions to produce sperm cells.

Meiosis represents a survival machinery for some simple eukaryotes such every bit
yeast. When weather are favorable, yeast reproduce asexually by mitosis. When nutrients become limited, notwithstanding, yeast enter meiosis. The commitment to meiosis enhances the
that the side by side generation will survive, because genetic recombination during meiosis generates 4 reproductive spores per jail cell, each of which has a novel
genotype. The entry of yeast into meiosis is a highly regulated process that involves pregnant changes in factor
et al., 2008). By analyzing yeast mutants that are unable to complete the various events of meiosis, investigators have been able to identify some of the molecules involved in this complex process. These controls have been strongly conserved during
development, and so such yeast experiments have provided valuable insight into meiosis in multicellular organisms as well.

In most multicellular organisms, meiosis is restricted to germ cells that are set aside in early
development. The germ cells reside in specialized environments provided by the gonads, or
sexual practice
organs. Within the gonads, the germ cells proliferate by mitosis until they receive the right signals to enter meiosis.

In mammals, the timing of meiosis differs greatly betwixt males and females (Figure 2). Male person germ cells, or spermatogonia, do non enter meiosis until subsequently puberty. Fifty-fifty then, only limited numbers of spermatogonia enter meiosis at whatever one time, such that adult males retain a puddle of actively dividing spermatogonia that acts as a stem cell population. On the other hand, meiosis occurs with quite different kinetics in mammalian females. Female person germ cells, or oogonia, stop dividing and enter meiosis within the fetal ovary. Those germ cells that enter meiosis get oocytes, the source of futurity eggs. Consequently, females are born with a finite number of oocytes arrested in the commencement meiotic
prophase. Within the ovary, these oocytes abound within follicle structures containing large numbers of support cells. The oocytes volition reenter meiosis only when they are ovulated in response to hormones. Human females, for example, are born with hundreds of thousands of oocytes that remain arrested in the get-go meiotic prophase for decades. Over time, the quality of the oocytes may deteriorate; indeed, researchers know that many oocytes die and disappear from ovaries in a procedure known as atresia.

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Meiosis Consists of a Reduction Sectionalisation and an Equational Division

Two divisions,
meiosis I
meiosis 2, are required to produce gametes (Effigy iii). Meiosis I is a unique
cell sectionalisation
that occurs only in germ cells; meiosis Ii is similar to a mitotic division. Before germ cells enter meiosis, they are by and large
diploid, significant that they take two
copies of each chromosome. Then, just before a germ cell enters meiosis, it duplicates its DNA so that the cell contains four Deoxyribonucleic acid copies distributed between two pairs of homologous chromosomes.

Meiosis I

A multi-panel diagram (labeled a through i) shows illustrations of a cell in five phases of Meiosis I and four phases of Meiosis II. Meiosis I begins with interphase, when a cell duplicates its DNA. Meiosis I then proceeds through prophase I, metaphase I, anaphase I, and telophase I. Meiosis I is followed by meiosis II. The stages of meiosis II include prophase II, metaphase II, anaphase II, and, finally, telophase II. At the end of Meiosis II, the single cell has divided to form four genetically unique daughter cells.

Compared to mitosis, which tin take place in a matter of minutes, meiosis is a irksome procedure, largely because of the time that the cell spends in
prophase I. During prophase I, the pairs of homologous chromosomes come together to form a
bivalent, which contains four chromatids. Recombination can occur between whatever two chromatids within this tetrad structure. (The recombination process is discussed in greater item later in this article.) Crossovers betwixt homologous chromatids can be visualized in structures known equally chiasmata, which appear late in prophase I (Figure 4). Chiasmata are essential for accurate meioses. In fact, cells that neglect to grade chiasmata may non exist able to segregate their chromosomes properly during
anaphase, thereby producing aneuploid gametes with abnormal numbers of chromosomes (Hassold & Hunt, 2001).

At the end of prometaphase I, meiotic cells enter
metaphase I. Here, in sharp contrast to mitosis, pairs of homologous chromosomes line up opposite each other on the
metaphase plate, with the kinetochores on
sis chromatids
facing the same pole. Pairs of
sex chromosomes
also align on the metaphase plate. In human being males, the
Y chromosome
pairs and crosses over with the 10 chromosome. These crossovers are possible because the X and Y chromosomes have pocket-sized regions of similarity near their tips. Crossover betwixt these homologous regions ensures that the sex chromosomes will segregate properly when the cell divides.

Next, during
anaphase I, the pairs of homologous chromosomes separate to different daughter cells. Before the pairs tin can separate, however, the crossovers betwixt chromosomes must be resolved and meiosis-specific cohesins must be released from the arms of the sis chromatids. Failure to separate the pairs of chromosomes to different daughter cells is referred to as
nondisjunction, and information technology is a major source of
aneuploidy. Overall, aneuploidy appears to be a relatively frequent event in humans. In fact, the
of aneuploidy in humans has been estimated to be as high every bit x% to 30%, and this frequency increases sharply with
historic period (Hassold & Hunt, 2001).

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Meiosis Two

An illustration of two homologous chromosomes shows crossing over during meiosis. One chromosome is green, and the other is orange. Each chromosome consists of two sister chromatids, which look like strands of pasta, connected at a junction called the centromere. The chromatids are shown crossing over each other at two places, which are labeled chiasmata. At these locations, the chromatids change color either from orange to green, or vice versa, to show the exchange of DNA between chromosomes during recombination.

Following meiosis I, the daughter cells enter meiosis II without passing through
or replicating their DNA. Meiosis II resembles a mitotic segmentation, except that the chromosome number has been reduced by half. Thus, the products of meiosis 2 are four
cells that contain a single copy of each chromosome.

In mammals, the number of feasible gametes obtained from meiosis differs betwixt males and females. In males, four haploid spermatids of similar size are produced from each
spermatogonium. In females, however, the cytoplasmic divisions that occur during meiosis are very asymmetric. Fully grown oocytes within the ovary are already much larger than sperm, and the future
retains virtually of this volume as information technology passes through meiosis. As a result, only one functional oocyte is obtained from each female meiosis (Figure 2). The other iii haploid cells are pinched off from the oocyte as polar bodies that contain very little cytoplasm.

Recombination Occurs During the Prolonged Prophase of Meiosis I

A schematic diagram shows the process by which double-stranded DNA breaks are fixed. A leftward pointing, horizontal arrow at the bottom of the diagram represents an increasing degree of interaction between the homologous chromosomes. During the leptotene portion, two homologous DNA strands are aligned. After a double-stranded break, one broken strand aligns with the complementary strand on the homologous DNA. Entering the zygotene phase, a bridge forms between the broken DNA and the complementary DNA strand. The broken strand then invades the complete strand, forming a synaptonemal complex. Then, in the pachytene phase, the broken strand is extended by DNA synthesis based on the complementary homologous strand. The synaptonemal complex is then stabilized by formation of a double Holliday junction.

Prophase I is the longest and arguably nearly of import segment of meiosis, because recombination occurs during this interval. For many years, cytologists have divided prophase I into multiple segments, based upon the appearance of the meiotic chromosomes. Thus, these scientists have described a
(from the Greek for “thin threads”) phase, which is followed sequentially by the
(from the Greek for “paired threads”),
(from the Greek for “thick threads”), and
(from the Greek for “two threads”) phases. In recent years, cytology and genetics take come together and then that researchers now sympathise some of the molecular events responsible for the stunning rearrangements of
observed during these phases.

Think that prophase I begins with the alignment of homologous chromosome pairs. Historically, alignment has been a hard problem to approach experimentally, but new techniques for visualizing private chromosomes with fluorescent probes are providing insights into the process. Recent experiments advise that chromosomes from some species have specific sequences that act as pairing centers for alignment. In some cases, alignment appears to begin as early as interphase, when homologous chromosomes occupy the same territory inside the interphase
(Figure 5). Nonetheless, in other species, including yeast and humans, chromosomes do not pair with each other until double-stranded breaks (DSBs) appear in the Dna (Gerton & Hawley, 2005). The formation of DSBs is catalyzed by highly conserved proteins with
activity that resemble the Spo11 protein from yeast. Genetic studies have shown that Spo11 activity is essential for meiosis in yeast, considering
mutants neglect to sporulate.

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Following the DSBs, one DNA strand is trimmed back, leaving a iii′-overhang that “invades” a homologous sequence on some other
chromatid. As the invading strand is extended, a remarkable construction called
synaptonemal complex
(SC) develops around the paired homologues and holds them in close register, or
synapsis. The
of the SC increases equally the invading strand first extends into the homologue and then is recaptured past the cleaved chromatid, forming double Holliday junctions. Investigators take been able to observe the process of SC formation with electron microscopy in meiocytes from the
establish (Figure 6). Bridges approximately 400 nanometers long begin to class between the paired homologues following the DSB. Just a fraction of these bridges volition mature into SC; moreover, not all Holliday junctions volition mature into crossover sites. Recombination volition thus occur at only a few sites along each chromosome, and the products of the crossover volition become visible every bit chiasmata in diplotene after the SC has disappeared (Zickler & Kleckner, 1999).

A series of electron photomicrographs shows the gradual formation of synaptonemal complex patches following double-stranded breaks in DNA. The photomicrographs are shown in a row from left to right. The three photomicrographs at left are enclosed in a pink box labeled \"nascent DSB; partner complex.\" The two photomicrographs at center are enclosed in a green box labeled \"onset of stable strand exchange.\" A final photomicrograph at right is enclosed in an orange box labeled \"CO nodule plus SC patch.\" Nascent DNA (pink box) appears as two horizontal black lines arranged in parallel with a bridge beginning to form between the two lines. When stable strand exchange occurs (green box), the upper DNA strand overlaps across the lower DNA strand, forming an X-shape. CO nodules and SC patches (orange box) hold the two recombined DNA strands closely together. The DNA looks like two horizontal, parallel lines with vertical lines connecting and spanning the space between them.

Figure 6: Visualization of chromosomal bridges in Allium fistulosum and Allium cepa (institute) meiocytes.

The sites of double-stranded break (DSB) dependent homologue interaction can be seen as approximately 400 nm bridges between chromosome axes. These bridges, which probably contain a DSB that is already engaged in a nascent interaction with its partner Deoxyribonucleic acid, occur in large numbers. Their formation depends on the RecA (recombination protein) homologues that are expressed in this species. In the adjacent phase of homologue interaction, these nascent interactions are converted to stable strand-invasion events. This nucleates the formation of the synaptonemal complex (SC).

© 2005 Nature Publishing Group Gerton, J. L. & Hawley, R. S. Homologous chromosome interactions in meiosis: multifariousness amongst conservation.
Nature Reviews Genetics
481 (2005). All rights reserved.

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References and Recommended Reading

Gerton, J. Fifty., & Hawley, R. S. Homologous chromosome interactions in meiosis: Multifariousness amidst conservation.
Nature Reviews Genetics
6, 477–487 (2005) doi:x.1038/nrg1614 (link to article)

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Lopez-Maury, 50., Marguerat, S., & Bahler, J. Tuning gene expression to irresolute environments: From rapid responses to evolutionary adaptation.
Nature Reviews Genetics
ix, 583–593 (2008) doi:10.1038/nrg2398 (link to article)

Marston, A. L., & Amon, A. Meiosis: Cell-wheel controls shuffle and deal.
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Zickler, D., & Kleckner, N. Meiotic chromosomes: Integrating structure and part.
Annual Review of Genetics
33, 603–754 (1999)

Crossing Over Prevents Homologous Chromosomes From Separating During Meiosis I