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Chapter 12
Chromosomal Basis of
Inheritance (Meiosis)
Copyright © 2010 Pearson Education Inc.
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Meiosis is two successive
divisions of a diploid nucleus
after only one DNA
replication cycle.
The result is haploid
gametes (animals) or
meiospores (plants).
The two rounds of division
are meiosis I and meiosis II,
each with a series of stages
Cytokinesis usually
accompanies meiosis,
producing four haploid cells
from a single diploid cell.
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Meiosis I is when the chromosome
information is reduced from diploid to
haploid. It has five stages.
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1. Prophase I is very similar to prophase of mitosis, except
that homologous chromosomes pair and undergo crossingover.
◦ i. Leptonema is when chromosomes begin to coil, committing the
cell to the meiotic process.
◦ ii. In zygonema, chromosomes continue to condense, and
synapsis, a tight association between homologous chromosomes,
occurs. Telomeres are important in synapsis.
◦ iii. Pachynema occurs when synapsis is reached. The fourchromatid synaptonemal tetrad facilitates crossing-over.
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Crossing-over is reciprocal exchange of
chromosome segments between
homologous chromosomes. If the
homologs are not identical, new gene
combinations (recombinant chromosomes)
can result, but usually no genetic material
is added or lost.
◦ v. Diplonema is the period when
chromosomes begin to move apart, and
chiasmata (singular is chiasma) become
visible.
 (1) Human oocytes arrest in diplonema in the
seventh month of fetal development
 (2) Preparation for ovulation takes the oocyte
through meiosis I.
 (3) Fertilization causes meiosis II to occur, allowing
fusion with the sperm nucleus to form a zygote.
◦ vi.Diakinesis involves chromosomes
condensing even more, and at this stage
they are most easily counted.
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Prometaphase I: breakdown of the
nucleoli and nuclear envelope and entry
of the meiotic spindle into the former
nuclear area. Kinetochore microtubules
attach to the chromosomes.
Metaphase I: has kinetochore microtubules
aligning tetrads on the metaphase plate.
◦ Difference from metaphase of mitosis: pairs of
homologous chromosomes align together to form
tetrads.
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Anaphase I: tetrads separate,
with chromosomes of each
homologous pair disjoining.
Resulting dyads migrate toward
opposite poles.
This migration assumes that:
◦ i. Centromeres derived from each
parent will migrate randomly toward
each pole.
◦ ii. Each pole will receive a haploid
complement of replicated
centromeres with associated
chromosomes.
◦ iii. Sister chromatids will remain
attached to each other (the major
difference from mitosis).
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Telophase I has dyads completing migration
to the poles, and usually a nuclear envelope
forms around each haploid grouping.
Cytokinesis follows in most species, forming
two haploid cells.
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Meiosis II is very similar to mitotic division.
◦ a. Prophase II: chromosomes condense and
spindle forms.
◦ b. Prometaphase II: nuclear envelopes (if any)
break down, spindle organizes with kinetochore
microtubules from opposite poles attached to
kinetochores of each chromosome.
◦ c. Metaphase II: chromosomes line up on
metaphase plate.
◦ d. Anaphase II: centromeres separate, and sister
chromatids are pulled to opposite poles.
◦ e. Telophase II: nuclear envelope forms around
each set of chromosomes.
◦ f. Cytokinesis usually takes place, and
chromosomes become elongated and invisible
with light microscopy.
After both rounds of meiotic division, four
haploid cells (gametes in animals) are usually
produced. Each has one chromosome from each
homologous pair, but these are not exact copies
due to crossing-over.
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Meiosis has three significant results:
a. Haploid cells are produced:
b. Alignment of paternally and maternally derived chromosomes is
random in metaphase I.
◦ i. The number of possible chromosome
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arrangements at the metaphase I plate is
2n-1 (n is the number of chromosome pairs).
ii. The number of possible chromosome
combinations in nuclei produced by meiosis
is 2n. (23 chromosomes= > 4million
combinations)
iii. Due to differences between paternally
and maternally derived chromosomes, many
possibilities exist. Nuclei produced by
meiosis will be genetically distinct from
parental cells and from one another.
c. Crossing-over between maternal
and paternal chromatid pairs during
meiosis I provides still more
variation, making the number of
possible progeny nuclei extremely
large.
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In diploid animals, the only haploid cells
are gametes produced by meiosis and
used in sexual reproduction. Gametes
are produced by specialized cells.
◦ i. In males, spermatogenesis produces
spermatozoa within the testes.
 (1) Primordial germ cells (primary
spermatogonia) undergo mitosis to produce
secondary spermatogonia.
 (2) Secondary spermatogonia transform into
primary spermatocytes (meiocytes), which
undergo meiosis I, giving rise to two
secondary spermatocytes.
 (3) Each secondary spermatocyte undergoes
meiosis II, producing haploid spermatids that
differentiate into spermatozoa.
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ii. In females, oogenesis produces eggs
(oocytes) in the ovary.
 (1) Primordial germ cells (primary oogonia)
undergo mitosis to produce secondary
oogonia.
 (2) Secondary oogonia transform into primary
oocytes, which grow until the end of
oogenesis.
 (3) Primary oocytes undergo meiosis I and
unequal cytokinesis, producing large
secondary oocyte and a small cell called first
polar body.
 (4) The secondary oocyte produces two
haploid cells in meiosis II. One very small cell,
the second apolar body, the other rapidly
matures into an ovum.
 (5) The first polar body may or may not divide
during meiosis I. Polar bodies have no, so a
round of meiosis produces only one viable
gamete, the ovum. Human oocytes form in
the fetus, completing meiosis only after
fertilization.
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Sexually reproducing plants typically
have two phases: gametophyte (haploid),
in which gametes are produced, and
sporophyte (diploid), in which meiosis
produces haploid spores.
◦ i. Angiosperms (flowering plants)
contain stamens (male) and pistils
(female) in either the same or different
flowers.
 (1) Stamens consist of a stalk (filament)
and anther. Pollen grains are immature
gametophytes (gamete-producing
structures).
 (2) The pistil consists of a stigma (the
surface to which pollen sticks); a style,
down which the pollen tube grows; and
an ovary at the base that contains the
ovules. Each ovule contains a female
gametophyte (embryo sac) with a single
egg cell. After fertilization, the ovule
develops into a seed.
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ii. Plants are unique among living
organisms in producing gametes from
gametophytes. The two distinct
reproductive phases are called
alternation of generations, with
meiosis and fertilization the transition
points between stages.
◦ (1) Meiosis creates haploid spores that
produce the haploid gametophyte
generation. In angiosperms, the spores
become the pollen and embryo sac that
are used in fertilization.
◦ (2) Fertilization begins the diploid
sporophyte generation, producing a
plant that will ultimately make spores
by meiosis, completing the cycle.
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Chromosome number is constant in
all cells of a species but varies
widely between species.
The chromosome theory of
inheritance states that Mendelian
factors (genes) are located on
chromosomes.
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Behavior of sex chromosomes offers support for the
chromosomal theory. In many animals sex
chromosome composition relates to sex, while
autosomes are constant.
McClung, Stevens, and Wilson indicated that
chromosomes are different in male and female
insects.
◦ a. Stevens named the extra chromosome found in females “X.”
◦ b. In grasshoppers, all eggs have an X; and half of the sperm
produced have an X, and the other half do not. After
fertilization, an unpaired X produces a male, while paired X
chromosomes produce a female.
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Other insects have a partner for the X chromosome.
Stevens named it “Y.” In mealworms, for example, XX
individuals are female, and XY are male.
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In both humans and fruit flies
(Drosophila melanogaster) females
have two X chromosomes, while
males have X and Y.
◦ a. Males produce two kinds of gametes
with respect to sex chromosomes (X or Y)
heterogametic sex.
◦ b. Females produce gametes with only one
kind of sex chromosome (X) homogametic
sex.
◦ c. In some species the situation is reversed,
with heterogametic females and
homogametic males.
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Random fusion of gametes produces
an F1 that is 1⁄2 female (XX) and 1⁄2 male
(XY).
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Morgan (1910) found a mutant whiteeyed male fly and used it in
experiments that showed a gene for
eye color located on the X
chromosome.
◦ a. First cross the white-eyed male with a
wild-type (red-eyed) female. All F1 flies are
red eyes. The white-eyed trait is recessive.
◦ b. Next, F1 were interbred. They produced
an F2 with:
 i. 3,470 red-eyed flies.
 ii. 782 white-eyed flies.
◦ c. The recessive number is too small to fit
Mendelian ratios (the explanation,
discovered later, is that white-eyed flies
have lower viability).
◦ d. All of the F2 white-eyed flies were male.
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This eye color gene is located on the X
chromosome.
◦ i. Males are hemizygous, no homologous gene on the Y.
Mutant male’s genotype was w/Y (hemizygous with the
recessive allele).
◦ ii. Females may be homozygous or heterozygous. The
wild-type female in the original cross was w+/w+
(homozygous for red eyes).
◦ iii. The F1 flies w+/w (females), w+/Y (males) (females all
heterozygous, males hemizygous dominant).
◦ iv. The F2 data complete a crisscross inheritance pattern,
with transmission from the mutant fly through his
daughter (who is heterozygous) to his grandson. The F2
were: 1 w+/w+; 1 w/w+; 1w+/Y; 1 w/Y.
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Confirmed by an experiment reciprocal
to the original cross. A white-eyed
female (w/w) was crossed with a wildtype male (w+/Y). Results of the
reciprocal cross:
◦ (1) All F1 females had red eyes (w+/w).
◦ (2) All F1 males had white eyes (w/Y).
These F1 results are different from
those in the original cross, where all
the F1 had red eyes. When the F1 from
the reciprocal cross interbred, the F2
were: 1/4 w+/w; 1/4 w+/Y; 1/4 w/w;
1/4 w/Y
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Morgan’s discovery of X-linked inheritance
showed that when results of reciprocal
crosses are different, and ratios differ
between progeny of different sexes, the gene
involved is likely to be X-linked (sex-linked).
This was strong evidence that genes are
located on chromosomes. Morgan received
the 1933 Nobel Prize for Physiology or
Medicine for this work.
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Bridges, found that about 1 in 2,000 of the
offspring was an exception from the crossing
a white-eyed female (w/w) with a red-eyed
male (w+/Y) that produces an F1 of whiteeyed males (w/Y) and red-eyed females
(w+/w).
Either a white-eyed female or red-eyed male.
Bridges’s hypothesis was that chromatids
failed to separate normally during anaphase
of meiosis I or II, resulting in nondisjunction.
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Nondisjunction can involve either autosomes or
sex chromosomes. For the eye color trait, X
chromosome nondisjunction was the relevant
event. Nondisjunction in an individual with a
normal set of chromosomes is called primary
nondisjunction.
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Nondisjunction, a rare event, in a w/w
female would result in eggs with two X
chromosomes (XX) and those with none
(O).
If these are fertilized with normal sperm
from a wild-type male (w+/Y), the
results are:
◦ i. YO, which die due to lack of an X
chromosome.
◦ ii. XXX, which die, presumably due to the
extra dose of X genes.
◦ iii. Red-eyed Xw+O sterile males who
received Xw+ from the father and no sex
chromosome from the mother.
◦ iv. White-eyed XwXwY females that received
two Xw chromosomes from the mother and Y
from the father.
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Bridges crossed the white-eyed
female (XwXwY) with wild-type
males (Xw+Y). The progeny were:
◦ i. XwXw+ and XwXw+Y females
with red eyes, which received the
Xw+ chromosome from the father,
and Xw or XwY from the mother.
◦ ii. Rarely, males with red eyes.
◦ iii. Rarely, females with white eyes.
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Secondary nondisjunction had
occurred, producing eggs with
either XwXw or Y.
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Secondary nondisjunction had
occurred, producing eggs
with either XwXw or Y.
When these eggs are fertilized
by normal sperm, XXX and YY
won’t survive, but an XwXw
egg united with a Y-bearing
sperm becomes a white-eyed
female, while a Y-bearing egg
united with an Xw+-bearing
sperm produces a red-eyed
male.
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The odd inheritance pattern matches
specific aneuploid types (XO and
XXY), clearly associating a specific
phenotype with a specific
chromosome complement.
Thus, gene segregation mirrors
chromosome behavior in meiosis.
Mendel’s principles of segregation
and independent assortment of genes
correlate with the movement of
chromosomes during meiosis.
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Some mechanisms of sex determination include:
◦ a. Genotypic sex determination, in which sex is governed
by genotype.
◦ b.Genic sex determination, in which sex chromosomes are
not involved.
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Sex Determination in Mammals
◦ Mammals use the Y-chromosome mechanism of
sex-determination, in which the Y chromosome
determines sex by conferring maleness.
◦ Sex of mammals is determined by a gene on the Y
chromosome, testis-determining factor. In the
absence of this gene, gonads develop into ovaries.
◦ XO individuals, sterile females exhibiting
Turner syndrome. Most XO fetuses die
before birth. Surviving Turner syndrome
individuals become noticeable at puberty,
when secondary sexual characteristics fail
to develop and:
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i. Below-average height.
ii. Weblike necks.
iii. Poorly developed breasts.
iv. Immature internal sexual organs.
v. Reduced ability to interpret spatial
relationships.
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XXY individuals, who are male
and have Klinefelter syndrome
Other traits include:
◦ i. Above-average height.
◦ ii. Breast development in about
50% of XXY individuals.
◦ Iii. Subnormal intelligence in some
cases.
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Gene dosage varies between the sexes in
mammals.
Females have two copies of X while males have
one.
Early in development, gene expression from the X
chromosome must be equalized to avoid death.
Different dosage compensation systems have
evolved in different organisms.
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Female somatic cell nuclei contain a Barr body
(highly condensed chromatin) while male nuclei
do not. The Lyon hypothesis explains the
phenomenon:
◦ a. A Barr body is a condensed and (mostly)
inactivated X chromosome. Lyonization of one
chromosome leaves one transcriptionally active X,
equalizing gene dose between the sexes.
◦ b. An X is randomly chosen in each cell for
inactivation early in development (in humans, day
16 postfertilization).
◦ c. Descendants of that cell will have the same X
inactivated, making female mammals genetic
mosaics. Examples are:
 i. Calico cats, in which differing descendant cells produce
patches of different color on the animal.
 ii. Women heterozygous for an X-linked allele responsible for
sweat glands; these women have a mosaic of normal skin and
patches lacking sweat glands (anhidrotic ectodermal displasia).
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Lyonization allows extra sex chromosomes to
be tolerated well. No such mechanism exists
for autosomes and so an extra autosome is
usually lethal.
The number of Barr bodies is the number of X
chromosomes minus one.
X inactivation involves three steps:
◦ i. Chromosome counting (determining number of Xs
in the cell).
◦ ii. Selection of an X for inactivation.
◦ iii. Inactivation itself.
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Selection of an X for inactivation is made by the Xcontrolling element (Xce) in the Xic region. There
are different alleles of Xce, and each allele has a
different probability that the X chromosome
carrying it will be inactivated.
◦ i. The gene Xist is required for X inactivation. Uniquely, it
is expressed from the inactive X.
◦ ii. The Xist gene transcript is 17 kb. Although it has no
ORFs, it receives splicing and a poly(A) tail.
◦ iii. During X inactivation, this RNA coats the chromosome
to be inactivated and silences most of its genes.
◦ iv. Inactivation itself is not well understood, but it is
known that it is initiated at the Xic and moves in both
directions, ultimately resulting in heterochromatin.
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An X chromosome–autosome
balance system is used.
Sex is determined by the ratio
between the number of X
chromosomes and the number
of sets of autosomes.
Drosophila has three pairs of
autosomes and one pair of sex
chromosomes. Like humans, XX
is female and XY is male. Unlike
humans, Y does not determine
sex, but it is required for male
fertility.
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An XXY fly is female, and an XO fly is male. The sex of
the fly results from the ratio of the number of X
chromosomes (X) to the number of sets of autosomes
(A):
◦ i. In a normal (diploid) female Drosophila, A=2 and X=2. The
X:A ratio is 1.0.
◦ ii. In a normal (diploid) male Drosophila, A=2 and X=1. The X:A
ratio is 0.5.
◦ iii. In cases of aneuploidy (abnormal chromosome numbers):
 (1) When the X:A ratio is ≥1.0, the fly is female.
 (2) When the X:A ratio is =0.5, the fly is male.
 (3) A ratio between 0.5 and 1.0 results in a sterile intersex fly with
mixed male and female traits.
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Dosage compensation in Drosophila results in more
expression of X-linked genes in males, so the level of
transcription equals that from a female’s two X
chromosomes
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Sex chromosome composition in birds, butterflies, moths, and
some fish is opposite that of mammals, with the male the
homogametic sex (ZZ) and the female heterogametic (ZW).
◦ a. Z-linked genes behave like X-linked genes in mammals, but the sexes
are reversed.
◦ b. The genes on the Z and W chromosomes are very different from those
on X and Y, indicating that these sex chromosomes evolved
independently, from different pairs of autosomes.
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In plants, the arrangement of sex organs varies:
◦ a. Dioecious species (e.g., ginkgo) have plants of separate sexes, one with
male parts, the other with female.
◦ b. Monoecious species have male and female parts on the same plant.
 i. Perfect flowers (e.g., rose, buttercup) have both types of parts in the same
flower.
 ii. Imperfect flowers (e.g., corn) have male and female parts in different flowers
on the same plant.
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Some dioecious plants have sex chromosomes and use an X
chromosome–autosome balance system, but many other sex
determination systems also occur in dioecious plants.
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Other eukaryotes use a genic system instead of
entire sex chromosomes. A single allele determines
the mating type (e.g., MATa and MATα in
Saccharomyces cerevisiae).
Yeast mating types have identical morphologies,
but are able to fertilize gametes only from the
opposite mating type.
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X-linked traits, like autosomal ones, can be
analyzed using pedigrees. Human pedigree
analysis, however, is complicated by several
factors:
◦ a. Data collection often relies on family recollections.
◦ b.If the trait is rare and the family small, there may not be
enough affected individuals to establish a mechanism of
inheritance.
◦ c. Expression of the trait may vary, resulting in affected
individuals being classified as normal.
◦ d.More than one mutation may result in the same
phenotype, and comparison of different pedigrees may
show different inheritance for the “same” trait.
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Human traits involving recessive
alleles on the X chromosome are Xlinked recessive traits.
A famous example is hemophilia A
among Queen Victoria’s
descendants.
X-linked recessive traits occur
much more frequently among
males, who are hemizygous. A
female would express a recessive
X-linked trait only if she were
homozygous recessive at that
locus.
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Affected fathers transmit the recessive allele to all
daughters (who are therefore carriers) and to none of
their sons.
Father-to-son transmission of X-linked alleles
generally does not occur.
Many more males than females exhibit the trait.
All sons of affected (homozygous recessive) mothers
are expected to show the trait.
With a carrier mother, about 1⁄2 of her sons will show
the trait and 1⁄2 will be free of the allele.
A carrier female crossed with a normal male will have 1⁄2
carrier and 1⁄2 normal daughters.
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Only a few X-linked dominants
are known.
◦ a. Hereditary enamel hypoplasia.
◦ b. Webbing to the tips of the toes.
◦ c. Constitutional thrombopathy
(severe bleeding due to lack of blood
platelets).
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Patterns of inheritance are the
same as X-linked recessives,
except that heterozygous
females show the trait (although
often in a milder form).
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Y-linked (holandric) traits, except for maleness
itself (resulting from SRY on the Y chromosome),
have not been confirmed, but many genes on the
Y chromosome have been identified.
The hairy ears trait may be Y linked, but it is a
complex phenotype that might also be the result
of autosomal gene(s) and/or effects of
testosterone.