9-0 Overview: The Meiotic Cell Cycle
Sexual reproduction is based on the fusion of haploid cells
homologs
B b
A a Diploid
D parent
d
meiosis
Haploid
gamete
b'
a'
d'
gamete fusion
haploid gamete
from second parent
Diploid
zygote
Figure 9-0.1 The sexual reproductive cycle
The diploid cell at top contains three different
chromosomes, each with two homologs
(labeled A and a, B and b, D and d). The meiotic
cell cycle reduces the number of chromosomes
by half, resulting in haploid gametes containing
one homolog of each chromosome. Fusion with
a gamete from another parent regenerates the
diploid state and completes the cycle. Meiosis
can generate any combination of homologs in
the gametes; only one combination is shown
here. Meiotic recombination between homologs
(not shown) also contributes to genetic
variation in the gametes.
Definitions
chiasmata: sites of crossing-over between homolo-
gous chromosomes in the first meiotic division.
diploid: containing two copies of each chromosome.
haploid: containing one copy of each chromosome.
nondisjunction: errors in chromosome segregation
during meiosis.
pairing: the gradual process by which homologous chro-
mosomes associate with each other in meiotic prophase.
1 Chapter 9 Meiosis
Most eukaryotic organisms proliferate by sexual reproduction, whereby the genomes of two
parents are mixed to generate offspring whose genetic makeup is related to that of siblings
and the parents, but still unique. This process depends on meiosis, a specialized cell divi-
sion that reduces the genome size by half, thereby giving rise to gametes—the egg and sperm
of metazoans, for example.
The cells of sexually-reproducing organisms are generally diploid: that is, they contain two
slightly different copies—called homologs—of each chromosome, one from each parent. The
process of sexual reproduction begins when diploid cells undergo meiosis to generate haploid
gametes carrying only a single homolog of each chromosome. The reproductive cycle is com-
pleted when haploid cells from two parents fuse to form a diploid zygote with a combination
of homologous chromosomes from the parents (Figure 9-0.1).
In multicellular organisms, meiosis occurs only in a small population of cells—the germ line—
to produce non-proliferative gametes. Most cells—the somatic cells—are diploid and reproduce
only by the mitotic cell cycle. In many unicellular organisms, however, all cells can alternate
between a mitotic and meiotic cell cycle, depending in most cases on environmental condi-
tions. Diploid yeast, for example, switch from a mitotic to a meiotic cycle when nutrients
become scarce, as discussed in Chapter 2 (see section 2-1).
Meiosis involves two rounds of chromosome segregation
The meiotic cell cycle (Figure 9-0.2) begins with a round of chromosome duplication—pre-
meiotic S phase—that gives rise to tightly linked sister-chromatid pairs. The cell then contains
two copies of each parental homolog, or a total of four chromatids for each chromosome
type. Two rounds of chromosome segregation—meiosis I and II—then distribute these four
chromatids into four haploid cells.
The first meiotic division solves the central problem of meiosis: segregation of homologous
chromosomes. This process is based on the same principles that govern sister-chromatid segre-
gation in mitosis. First, the homologs must be attached to each other, and second, they must
be aligned on a spindle with each homolog attached to the opposite spindle pole.
Homolog attachment occurs after premeiotic S phase, in a stage called meiotic prophase. This
stage begins with homolog pairing, which involves interactions between complementary
DNA sequences in the two homologs. Pairing is followed by synapsis, whereby the
homologs are linked tightly along their entire length by a protein scaffold called the synap-
tonemal complex. This complex dissolves late in prophase, but homologs remain linked at
sites of DNA recombination, as discussed below. These homolog pairs, each containing four
chromatids, are called bivalents.
Following meiotic prophase, homolog pairs are attached to the first meiotic spindle. Because
each homolog contains two sister chromatids, both kinetochores of a sister-chromatid pair
must attach to the same spindle pole, while the homologous sister pair attaches to the oppo-
site pole. Homologs are segregated in anaphase I, and the spindle is disassembled in telophase
I. The first meiotic division is sometimes called reductional division, because the resulting cells
contain only one copy of each parental homolog (each present in duplicate) and are therefore
reduced to a genetically haploid state.
synapsis: during meiotic prophase, the tight linkage of References
homologous chromosomes by the assembly of the
synaptonemal complex. John, B.: Meiosis (Cambridge University Press, New York,
1990).
Page, S.L. and Hawley, R.S.: Chromosome choreogra-
phy: the meiotic ballet. Science 2003, 301:785–789.
Zickler, D. and Kleckner, N.: Meiotic chromosomes:
integrating structure and function. Annu. Rev. Genet.
1999, 33:603–754.
©2004 New Science Press Ltd
 Overview: The Meiotic Cell Cycle 9-0
Exit from meiosis I leads directly to the second meiotic division. Meiosis II resembles mitosis,
in that sister chromatid pairs are aligned on a spindle with each chromatid attached to oppo-
site poles. Segregation of sister chromatids in anaphase II distributes the sister chromatids into Diploid
four haploid cells. The number of homologs is not reduced in meiosis II, and so this division parent
is sometimes called equational division.

Genetic recombination is an important feature of meiosis premeiotic S phase

Meiosis is an important source of genetic variation in sexually reproducing organisms.

During the first meiotic division, a random assortment of homologs is distributed to the
daughter cells (Figure 9-0.1). Thus, in organisms with many chromosomes, haploid gametes
may contain any one of a large number of possible combinations of maternal and paternal
homologs.
Another major source of genetic variation in meiosis is DNA recombination, which results in
the reciprocal exchange of DNA segments between paired homologs. Recombination occurs
during homolog pairing and synapsis in meiotic prophase and results in chromosomal crossing- meiotic prophase
over: that is, the DNA strand from one chromatid crosses over to join the complementary
DNA of one copy of the other homolog (Figure 9-0.2). Typically, one to four of these
crossovers occur in each human bivalent.
synaptonemal
complex
When the synaptonemal complex dissolves late in meiotic prophase, crossovers continue to crossover
hold the homologs together at sites called chiasmata (singular chiasma). Chiasmata hold
homologs together only because sister-chromatid arms distal to chiasmata are tightly linked
by cohesins. Homologs are therefore separated in anaphase I by removal of cohesins from sis-
ter-chromatid arms—while cohesion is maintained at centromeres to allow sister segregation entry into meiosis I
in meiosis II. As in mitosis, these linkages between chromosomes are essential for accurate
segregation in both meiotic divisions.
first
The males of most animal species contain two different sex chromosomes, X and Y, that are meiotic
spindle
generally not homologous to each other but must be segregated like homologs in meiosis I. chiasma
Pairing of X and Y chromosomes depends on small regions of DNA sequence homology
near their ends, where pairing, synapsis and recombination occur—thereby ensuring their
accurate segregation.
homolog separation
Defects in meiosis lead to aneuploidy

Errors in meiotic chromosome segregation—called nondisjunction—can lead to abnormali-

ties in the number of chromosomes in the gametes. The most common problem is the gain or
loss of a single chromosome (aneuploidy). Several percent of human oocytes and sperm are ane-
uploid, and the frequency of errors increases with age. Aneuploid zygotes generally fail to sur-
vive, and meiotic segregation errors probably account for nearly half of the spontaneous abor-
tions, or miscarriages, that often occur in the first trimester of pregnancy. In some cases, ane-
uploid gametes give rise to a viable but partially defective embryo. Embryos with three copies entry into meiosis II second
meiotic
of chromosome 21, for example, develop into children with mental retardation and altered spindle
physical appearance (Down’s syndrome).

Figure 9-0.2 The meiotic cell cycle The diploid cell shown here has only one chromosome, completion of meiosis II
represented by two homologs. Premeiotic S phase results in two sister chromatids per homolog, linked
tightly by cohesins along their entire length. In meiotic prophase, homolog pairing and synapsis are
accompanied by DNA recombination, resulting in crossovers that become visible as chiasmata after the
synaptonemal complex dissolves. As homolog pairs are bioriented in meiosis I, they are held together
only by cohesion along sister-chromatid arms distal to the chiasmata. Loss of arm cohesion therefore
results in homolog separation in anaphase I. Sister chromatids are then segregated in meiosis II. Note
that meiotic prophase is sometimes defined as the first stage of meiosis I. For clarity, meiosis I is Gametes
defined in this chapter as those events that are equivalent to the central events of mitosis, beginning
with the onset of spindle assembly and followed by chromosome attachment and segregation. As
discussed later in this chapter (section 9-1), studies of the meiotic control system also suggest that
meiotic prophase and meiosis I are distinct stages governed by different regulators.

©2004 New Science Press Ltd Meiosis Chapter 9 2