Download CHAPTER 12 Chromosomal Basis of Inheritance, Sex linkage

Peter J. Russell
A molecular Approach 2nd Edition
CHAPTER 12
Chromosomal Basis of Inheritance,
Sex Linkage, and Sex Determination
edited by Yue-Wen Wang Ph. D.
Dept. of Agronomy,台大農藝系
NTU
遺傳學 601 20000
Chapter 11 slide 1
Chromosomes and Cellular Reproduction
1. Cytology and genetics together were used to
determine the association of genes and
chromosomes.
2. Eukaryotic chromosomes are transmitted during
cell division by mitosis and during reproduction
by meiosis.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 2
Eukaryotic Chromosomes
1. Eukaryotes have multiple linear chromosomes in a
number characteristic of the species. Most have two
versions of each chromosome, and so are diploid (2N).
a. Diploid cells are produced by haploid (N) gametes that fuse to
form a zygote. The zygote then undergoes development, forming
a new individual.
b. Examples of diploid organisms are humans (23 pairs) and
Drosophila melanogaster (4 pairs). The yeast Saccharomyces
cerevisiae is haploid (16 chromosomes).
台大農藝系 遺傳學 601 20000
Chapter 11 slide 3
Eukaryotic Chromosomes
2. Chromosome pairs in diploid organisms are
homologous chromosomes. One member of each
pair (homolog) is inherited from each parent.
Chromosomes that have different genes and do
not pair are nonhomologous chromosomes
(Figure 12.1).
台大農藝系 遺傳學 601 20000
Chapter 11 slide 4
Eukaryotic Chromosomes
3. Animals and some plants have male and female
cells with distinct chromosome sets, due to sex
chromosomes. One sex has a matched pair (e.g.,
human females with XX) and the other has an
unmatched pair (human male with XY).
Autosomes are chromosomes other than sex
chromosomes.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 5
Eukaryotic Chromosomes
4. Chromosomes differ in size and morphology.
Each has a constriction called a centromere that is
used in segregation during mitosis and meiosis.
The centromere location is useful for identifying
chromosomes (Figure 12.2).
台大農藝系 遺傳學 601 20000
Chapter 11 slide 6
Eukaryotic Chromosomes
a. Metacentric means the centromere is approximately in
the center of the chromosome, producing two equal
arms.
b. Submetacentric means one arm is somewhat longer
than the other.
c. Acrocentric chromosomes have one long arm and a
short stalk and often a bulb (satellite) as the other arm.
d. Telocentric chromosomes have only one arm, because
the centromere is at the end.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 7
Eukaryotic Chromosomes
5. A karyotype shows the complete set of chromosomes in a
cell. Metaphase chromosomes are used because they are
easiest to see under the microscope after staining. The
karyotype is species-specific.
a. The karyotype for a normal human male has 22 pairs of
autosomes, and 1 each of X and Y (Figure 12.3).
b. Human chromosomes are numbered from largest (1) to smallest
(although 21 is actually smaller than 22).
c. Human chromosomes with similar morphologies are grouped (A
through G).
台大農藝系 遺傳學 601 20000
Chapter 11 slide 8
台大農藝系 遺傳學 601 20000
Chapter 11 slide 9
Eukaryotic Chromosomes
d. Staining produces bands on the chromosomes,
allowing easier identification. G banding is an
example.
i. Chromosomes are partially digested with proteolytic
enzymes or treated with mild heat, and then stained
with Giemsa stain. The dark bands produced are G
bands.
ii. In humans, metaphase chromosomes show about 300
G bands, while about 2,000 can be distinguished in
prophase.
iii. Drawings (ideograms) show the G banding pattern of
human chromosomes.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 10
Eukaryotic Chromosomes
iv. Standard nomenclature is used to reference specific regions of
the chromosomes.
(1) The two arms are separated by the centromere, with the
smaller one designated p and the larger q.
(2) Regions and subregions are numbered from the centromere
outward (1 is closest).
(3) An example is the BRCA1 (breast cancer susceptibility)
gene at 17q21 (long arm of chromosome 17 in region 21).
(4) If a gene spans subregions, both are given. For example, the
human cystic fibrosis gene is at 7q31.2-q31.3, spanning both
subregions 2 and 3 on the long arm of chromosome 7.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 11
Mitosis
• Mitosis animation
台大農藝系 遺傳學 601 20000
Chapter 11 slide 12
Mitosis
1. Both unicellular and multicellular eukaryotes show a cell cycle, with
growth, mitosis and cell division.
a. The cycle of somatic cells consists of:
i. Mitosis.
ii. Interphase, composed of:
(1) Gap 1 (G1) when the cell prepares for chromosome replication.
(2) Synthesis (S) when DNA replicates and new chromosomes are
formed.
(3) Gap 2 (G2) when the cell prepares for mitosis and cell division.
b. Relative time in each phase varies among cell types, with duration of G1
generally the deciding factor. Some cells exit G1 and enter a nondividing state
called G0.
c. Interphase chromosomes are elongated and hard to see with light microscopy.
Sister chromatids are held together by replicated but unseparated centromeres.
The chromatids become visible in prophase and metaphase of mitosis. When
the centromeres separate, they become daughter chromosomes.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 13
Mitosis
2. Mitosis is a continuous process, but geneticists
divide it into 4 cytologically distinguishable
stages (Figures 12.5 and 12.6):
台大農藝系 遺傳學 601 20000
Chapter 11 slide 14
台大農藝系 遺傳學 601 20000
Chapter 11 slide 15
台大農藝系 遺傳學 601 20000
Chapter 11 slide 16
Prophase
is characterized by chromosomes condensing to a form visible by
light microscopy.
i. The mitotic spindle, composed of microtubules made of
tubulins, begins to form.
ii. In animal cells, the centrioles replicate and become the
focus for the aster (radial array of microtubules). During
prophase, asters move from near each other and the
nuclear envelope to the poles of the cell, spanned by the
mitotic spindle.
iii. The nucleoli in the nucleus cease to be discrete areas.
iv. The nuclear envelope breaks down.
v. Kinetochores form on the centromeres and become
attached to kinetochore microtubules.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 17
Metaphase
begins when the nuclear envelope has completely disappeared.
i. The kinetochore microtubules orient the
chromosomes with their centromeres in a plane
between the spindle poles, the metaphase plate.
ii. A protein scaffold causes the chromosomes to
reach a highly condensed state (Figure 12.17).
台大農藝系 遺傳學 601 20000
Chapter 11 slide 18
Anaphase
begins when the centromeres of the sister chromatids separate.
i. The chromatids separate (disjunction) and
daughter chromosomes move toward opposite
poles by kinetochore microtubules.
ii. Shape of the chromosomes moving toward the
poles is defined by their centromere locations.
iii. Cytokinesis usually begins near the end of
anaphase.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 19
Telophase
is when migration of daughter chromosomes is completed.
i. Chromosomes begin to uncoil and form interphase
chromosomes.
ii. Nuclear envelope forms around each
chromosome group.
iii. Spindle microtubules disappear.
iv. Nucleoli reform.
v. Nuclear division is complete.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 20
Cytokinesis
Cytokinesis is division of the cytoplasm,
compartmentalizing the new nuclei into separate
daughter cells (Figure 12.18).
a.
In animal cells,
cytokinesis begins with
a constriction in the
center of the cell, which
develops until two new
cells are produced.
b. Most plant cells form a
cell plate (membrane
and wall) between the
two nuclei, resulting in
台大農藝系
遺傳學
601 20000 cells
Chapter 11 slide 21
two
progeny
Mitosis
Gene segregation in mitosis is highly ordered, so
that each new cell receives a complete set of
chromosomes (pairs in a diploid cell, and one of
each type in a haploid cell).
台大農藝系 遺傳學 601 20000
Chapter 11 slide 22
Meiosis
Meiosis animation
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 in meiosis are
meiosis I and meiosis II, each with a series of
stages(Figure 12.9). Cytokinesis usually
accompanies meiosis, producing four haploid
cells from a single diploid cell.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 23
台大農藝系 遺傳學 601 20000
Chapter 11 slide 24
Meiosis I
is when the chromosome information is reduced from diploid to
haploid. It has four stages:
Prophase I
Leptonema
Zygonema
Pachynema
Diplonema
diakinesis
Metaphase I
Anaphase I
Telophase I
台大農藝系 遺傳學 601 20000
Chapter 11 slide 25
Meiosis I
Prophase I - leptonema
Prophase I is very similar to prophase of mitosis,
except that homologous chromosomes pair and
undergo crossing-over.
i. Leptonema is when chromosomes begin to coil,
committing the cell to the meiotic process.
Homologous chromosomes pair during the
leptomene stage.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 26
Meiosis I
Prophase I - zygonema
ii. 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.
iii. In zygonema, synapsis occurs. Synapsis is a tight
association between homologous chromosomes.
The synaptonemal complex consists of a tetrad of
the four chromatids at maximum condensation.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 27
Meiosis I
Prophase I - pachynema
iv. Pachynema follows, when the synaptonemal
complex is disassembled and chromosomes start
to elongate.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 28
Meiosis I
Prophase I - diplonema
v. Diplonema is when chromosomes begin to move
apart, and chiasmata (singular is chiasma) formed
by crossing-over become visible (Figure 12.10).
(1) Human oocytes arrest in diplonema in the 7th month
of fetal development, and remain there until an oocyte
is activated to prepare for ovulation.
(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.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 29
Meiosis I
Prophase I - diakinesis
vi. Diakinesis involves breakdown of the nucleoli
and nuclear envelope, and assembly of the
spindle. This is the phase where chromosomes are
most easily counted.
vii. Sex chromosomes are not homologous, but
behave as if they were due to a pseudoautosomal
region shared between X and Y.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 30
Meiosis I
metaphase I, anaphase I, telophase I
b. Metaphase I starts with the nuclear envelope completely broken down, bivalents
(pairs of homologs) aligned at the equatorial plane, the spindle completely
formed, and microtubules attached to kinetochores. It is distinguishable from
metaphase of mitosis because independent alignment of homologous
chromosomes does not occur.
c. Anaphase I is when bivalents separate, with chromosomes of each homologous
pair disjoining. Resulting dyads migrate toward opposite poles, where new
nuclei will form. 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).
d. Telophase I has dyads completing migration to the poles, and usually formation
of a nuclear envelope around each haploid grouping. Cytokinesis follows in
most species, forming two haploid cells.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 31
Meiosis II
is very similar to mitotic division.
a. Prophase II involves chromosome condensation.
b. Metaphase II includes spindle formation, with
centromeres lining up on the equator.
c. Anaphase II involves splitting of the centromeres, with
chromosomes pulled to opposite poles.
d. Telophase II takes place as a nuclear envelope forms
around each set of chromosomes.
e. Cytokinesis usually takes place, and chromosomes
become elongated and invisible with light microscopy.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 32
Meiosis v.s. mitosis
4. 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. Figure 12.11 compares
mitosis and meiosis.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 33
Meiosis has three significant results
a. Haploid cells are produced because two rounds of division follow only
one round of chromosome replication. Fusion of haploid cells restores
the diploid number, maintaining a constant chromosome number
through generations in sexually reproducing organisms.
b. Alignment of paternally and maternally derived chromosomes is random
in metaphase I, resulting in random combinations of chromosomes in
each nucleus generated (Figure 12.12).
i. The number of possible chromosome arrangements at the meiosis I
metaphase 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.
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.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 34
Meiosis in animals and plants is somewhat
distinct - animal
a. In diploid animals, the only haploid cells are gametes produced by meiosis and used in
sexual reproduction. Gametes are produced by specialized cells (Figure 1.26).
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.
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 a large secondary
oocyte, and a small cell called the first polar body.
(4) The secondary oocyte produces two haploid cells in meiosis II. One is a very small cell,
the second polar body, and the other rapidly matures into an ovum.
(5) The first polar body may or may not divide during meiosis I. Polar bodies have no
function in most species and degenerate, so that a round of meiosis produces only one
viable gamete, the ovum. Human oocytes form
in the fetus,
completing
meiosisChapter
only after
台大農藝系
遺傳學
601 20000
11 slide 35
fertilization.
Meiosis in animals and plants is somewhat
distinct - plant
b. 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, which releases pollen grains. Pollen
grains are immature gametophytes (gamete-producing structures).
(2) The pistil contains female gametophytes, and consists of a stigma (the surface to which
pollen sticks), a style, down which the pollen tube grows, and an ovary at the base which
contains the ovules. Each ovule contains a female gametophyte (embryo sac) with a single
egg cell. After fertilization, the ovule develops into a seed.
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 (Figure 12.15).
(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.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 36
Chromosome Theory of Inheritance
1. By the beginning of the 20th century, cytologists had
observed that chromosome number is constant in all
cells of a species, but varies widely between
species.
2. Sutton and Boveri (1902) independently realized the
parallel between Mendelian inheritance and
chromosome transmission, and proposed the
chromosome theory of inheritance, which states that
Mendelian factors (genes) are located on
chromosomes.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 37
Sex Chromosomes
1. Behavior of sex chromosomes offers support for the
chromosomal theory. In many animals sex chromosome
composition relates to sex, while autosomes are constant.
2. Independent work of 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.
3. 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.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 38
4. In both humans and fruit flies (Drosophila melanogaster)
females have two X chromosomes, while males have X
and Y (Figure 12.16).
a. Males produce two kinds of gametes with respect to sex
chromosomes (X or Y), and are called the heterogametic sex.
b. Females produce gametes with only one kind of sex
chromosome (X) and are called the homogametic sex.
c. In some species the situation is reversed, with heterogametic
females and homogametic males.
5. Random fusion of gametes (Figure 12.17) produces an F1
that is 1⁄2 female (XX) and 1⁄2 male (XY).
台大農藝系 遺傳學 601 20000
Chapter 11 slide 39
Fig. 12.16 Drosophila melanogaster (fruit fly), an organism used extensively in
genetics experiments
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 40
Fig. 11.17 Inheritance pattern of X and Y chromosomes in organisms where the female
is XX and the male is XY: Production of the F1 generation
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 41
Sex Linkage
Animation: X-Linked Inheritance
1. Morgan (1910) found a mutant white-eyed male fly, and used it in
a series of experiments that showed a gene for eye color located
on the X chromosome.
a. First, he crossed the white-eyed male with a wild-type (red-eyed)
female. All F1 flies had red eyes. Therefore, 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
(explanation discovered later is that white-eyed flies have lower
viability).
d. All of the F2 white-eyed flies were male.
e. Cross is diagramed in Figure 12.18, and Drosophila symbolism
is explained in Box 12.1.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 42
Fig. 12.18 X-linked inheritance of white eyes in Drosophila: Red-eyed female 
white-eyed male
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 43
f. Morgan’s hypothesis was that this eye color gene is located on
the X chromosome. If so,
i. Males are hemizygous, because there is no homologous
gene on the Y. The original mutant male’s genotype was w/Y
(hemizygous with the recessive allele).
ii. Females may be homozygous or heterozygous. The wildtype female in the original cross was w+/w+ (homozygous for
red eyes).
iii. The F1 flies were w+/w (females) and 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:
w+
Y
w+
w+/ w+
Red-eyed females
w+/ Y
Red-eyed males
w
w+/ w
Red-eyed females
w/ Y
White-eyed males Chapter 11 slide 44
台大農藝系 遺傳學 601 20000
v. Morgan’s hypothesis was confirmed by an experiment
reciprocal to the original cross(Figure 12.19). A whiteeyed female (w/w) was crossed with a wild-type 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).
vi. 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:
w
Y
w+
w+/ w
Red-eyed females
w+/ Y
Red-eyed males
w
w/ w
White-eyed females
w/ Y
White-eyed males
台大農藝系 遺傳學 601 20000
Chapter 11 slide 45
Fig. 12.19a Reciprocal cross of that shown in Figure 11.3: Homozygous white-eyed
female  red-eyed ( wild-type) male
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 46
Fig. 12.19b Reciprocal cross of that shown in Figure 11.3: The F1 flies are interbred to
produce the F2s
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 47
2.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).
3.This was strong evidence that genes are
located on chromosomes. Morgan received
the 1933 Nobel Prize for Physiology or
Medicine for this work.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 48
Non-Disjunction of X Chromosomes
Animation: Non-disjunction
1. Morgan’s work showed that crossing a white-eyed female (w/w)
with a red-eyed male (w+/Y) produces an F1 of white-eyed males
(w/Y) and red-eyed females (w+/w). His student, Bridges, found
that about 1 in 2,000 of the offspring was an exception, either a
white-eyed female or red-eyed male.
2. Bridges’ hypothesis was that chromatids failed to separate
normally during anaphase of meiosis I or II, resulting in nondisjunction.
3. Non-disjunction can involve either autosomes or sex
chromosomes. For the eye-color trait, X chromosome nondisjunction was the relevant event. Non-disjunction in an
individual with a normal set of chromosomes is called primary
non-disjunction (Figure 12.20).
台大農藝系 遺傳學 601 20000
Chapter 11 slide 49
Fig. 12.20 Nondisjunction in meiosis involving the X chromosome
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 50
4. Non-disjunction explains Bridges’ findings:
a. Non-disjunction, a rare event, in a w/w female would result in eggs with two X
chromosomes (XX), and those with none (O) (Figure 12.21).
b. 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 2 Xw chromosomes from the mother
and Y from the father.
c. Chromosomes of the exceptional flies matched the prediction: white-eyed females
were XXY, and red-eyed males XO. They show aneuploidy, meaning that 1 or more
chromosomes of a normal set are missing or present in unusual number.
+
d. 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, that 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.
e. He proposed that secondary non-disjunction had occurred, producing eggs with either
XwXw or Y(Figure 12.22). 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台大農藝系 遺傳學 601 20000
Chapter 11 slide 51
eyed male.
Fig. 12.22 a Rare primary nondisjunction during meiosis in a white-eyed female
Drosophila and results of a cross with a normal red-eyed male
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 52
Fig. 12.22b Results of a cross between the exceptional white-eyed XXY female of Figure
12.22a with a normal red-eyed XY male
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 53
5.The odd inheritance pattern matches specific
aneuploid types (XO and XXY), clearly
associating a specific phenotype with a
specific chromosome complement.
6.Thus, gene segregation mirrors chromosome
behavior in meiosis(Figure 12.23). Mendel’s
principles of segregation and independent
assortment of genes correlate with the
movement of chromosomes during meiosis.
Animation: Gene and Chromosome Segregation in
Meiosis
台大農藝系 遺傳學 601 20000
Chapter 11 slide 54
Fig. 12.23 The parallel behavior between Mendelian genes and chromosomes in meiosis
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 55
Sex Determination
1. 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.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 56
Genotypic Sex Determination Systems
1. Genotypic sex determination may occur two different
ways:
a. In the Y-chromosome mechanism of sex-determination
(e.g., in mammals), the Y chromosome determines sex,
conferring maleness.
b. In the X chromosome-autosome balance system (e.g.,
Drosophila, Caenorhabditis elegans) the ratio between
number of X chromosomes and number of sets of
autosomes determines sex. Y is required for male fertility,
but does not determine sex.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 57
Sex Determination in Mammals
1. Mammals use the Y-chromosome mechanism of
sex-determination, in which the Y chromosome
determines sex by conferring maleness.
2. 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.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 58
Evidence for the Y Chromosome Mechanism of
Sex Determination
1. Understanding of the Y chromosome mechanism of sex determination came from the study
of individuals with unusual chromosome complements. In humans these aneuploidies
include:
a. XO individuals, who are 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. Other traits include:
i. Below average height.
ii. Weblike necks.
iii. Poorly developed breasts.
iv. Immature internal sexual organs.
v. Reduced ability to interpret spatial relationships.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 59
b.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.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 60
c. XYY individuals are male, and
tend to be taller than average.
Fertility is sometimes affected.
d. XXX individuals are usually
normal women, although they
may be slightly less fertile and
a few have below average
intelligence.
e. Higher numbers of X and/or Y
chromosomes are sometimes
found, including XXXY, XXXXY,
and XXYY. The effects are
similar to Klinefelter syndrome.
Consequences of sex
chromosome aneuploidy in
humans are summarized in
Table 12.2.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 61
Dosage Compensation Mechanism for XLinked Genes in Mammals
1. Gene dosage varies between the sexes in mammals, because 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.
2. In mammals, female somatic cell nuclei contain a Barr body (highly
condensed chromatin) while male nuclei do not(Figure 12.26). The Lyon
hypothesis explains the phenomenon:
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).
台大農藝系 遺傳學 601 20000
Chapter 11 slide 62
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 (Figure
12.27).
ii. Women heterozygous for an X-linked allele
responsible for sweat glands, who have a mosaic of
normal skin and patches lacking sweat glands
(anhidrotic ectodermal displasia).
d. Lyonization allows extra sex chromosomes to be tolerated
well. No such mechanism exists for autosomes, and so an
extra autosome is usually lethal.
e. The number of Barr bodies is the number of X
chromosomes minus one (Table 12.2).
台大農藝系 遺傳學 601 20000
Chapter 11 slide 63
f. 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.
g. Counting the chromosomes involves the X-inactivation center (XIC in humans, Xic in
mice). Experiments in transgenic mice show that:
i. Inactivation requires the presence of at least two Xic sequences, one on each X
chromosome.
ii. Autosomes with an Xic inserted are randomly inactivated, showing that Xic is
sufficient for chromosome counting and initiation of lyonization.
h. Selection of an X for inactivation is made by the X-controlling 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.
i. The Xist gene transcript is 17-kb. Although it has no ORFs, it receives splicing
and a poly(A) tail.
ii. During X inactivation, this RNA coats the chromosome to be inactivated and
silences most of its genes.
iii. Inactivation itself is not well understood, but it is known that it initiates at the
Xic and moves in both directions, ultimately resulting in heterochromatin.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 64
Sex Determination in Drosophila
1. An X-chromosome-autosome balance system is used.
2. 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.
3. 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):
a. In a normal (diploid) female Drosophila, A=2 and X=2. The X:A ratio is 1.0.
b. In a normal (diploid) male Drosophila, A=2 and X=1. The X:A ratio is 0.5.
c. In cases of aneuploidy (abnormal chromosome numbers):
i. When the X:A ratio is ≧1.0, the fly is female.
ii. When the X:A ratio is≦0.5, the fly is male.
iii. A ratio between 0.5 and 1.0 results in a sterile intersex fly with mixed
male and female traits.
4. 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.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 65
Sex Determination in Caenorhabditis
1. C. elegans, the nematode, also uses the X-chromosomeautosome balance system to produce its two sexes,
hermaphrodites and males.
a. Self-fertilization in a hermaphrodite generally produces more
hermaphrodites; only 0.2% of the offspring are male.
b. Cross-fertilization between a hermaphrodite and a male
produces approximately equal numbers of hermaphrodites and
males.
2. Both hermaphrodites and males have five pairs of autosomes, so
hermaphrodites (XX) have an X-chromosome-autosome ratio of
1.0, while males (XO) have a ratio of 0.5.
3. Dosage compensation limits transcription from each X
chromosome of the hermaphrodite to 1⁄2 the level transcribed
from the single X chromosome in the male.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 66
Sex Chromosomes in Other Organisms
1. 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). Z-linked genes behave like Xlinked genes in mammals, but the sexes are reversed.
2. 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.
3. Some dioecious plants have sex chromosomes and use an Xchromosome-autosome balance system, but many other sex
determination systems also occur in dioecious plants.
4. 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).
台大農藝系 遺傳學 601 20000
Chapter 11 slide 67
Genic Sex Determination
1. Other eukaryotes use a genic system instead of
entire sex chromosomes. A single allele
determines the mating type (e.g., MATa and
MATa in Saccharomyces cerevisiae).
2. Yeast mating types have identical morphologies,
but are able to fertilize gametes only from the
opposite mating type.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 68
Environmental Sex Determination Systems
1. A few species use environmental sex determination systems, in
which environmental factors affect the sex of progeny.
2. Some types of turtles are an example. Eggs incubated above 32°
develop into females, while those below 28° become males. Eggs
between these temperatures produce a mix of the two sexes.
Details will vary with each species using this system.
3. In this system, the environment triggers a developmental
pathway which is under genetic control.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 69
Analysis of Sex-Linked Traits in Humans
iActivity: It Runs in the Family
1. 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.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 70
X-Linked Recessive Inheritance
1. Human traits involving recessive alleles on the X chromosome are
X-linked recessive traits. A famous example is hemophilia A among Queen
Victoria’s descendants (Figure 12.28).
2. 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.
3. Some characteristics of X-linked recessive inheritance:
a. Affected fathers transmit the recessive allele to all daughters (who are therefore
carriers), and to none of their sons.
b. Father-to-son transmission of X-linked alleles generally does not occur.
c. Many more males than females exhibit the trait.
d. All sons of affected (homozygous recessive) mothers are expected to show the trait.
e. With a carrier mother, about 1⁄2 of her sons will show the trait and 1⁄2 will be free of
the allele.
f. A carrier female crossed with a normal male will have 1⁄2 carrier and 1⁄2 normal
daughters.
4. Other X-linked recessive traits are Duchenne muscular dystrophy and two forms
of color blindness.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 71
Fig. 12.28 Pedigree of Queen Victoria (III-2) and her descendants, showing the Xlinked recessive inheritance of hemophilia
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 72
X-Linked Dominant Inheritance
1. Only a few X-linked dominants are known.
2. Examples include:
a. Hereditary enamel hypoplasia (faulty and discolored tooth
enamel)
b. Webbing to the tips of toes.
c. Constitutional thrombopathy (severe bleeding due to lack
of blood platelets).
3. Patterns of inheritance are the same as X-linked
recessives, except that heterozygous females show
the trait (although often in a milder form).
台大農藝系 遺傳學 601 20000
Chapter 11 slide 73
Fig. 11.14b Pedigree showing the transmission of the X-linked dominant trait of faulty
tooth enamel
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 74
Y-Linked Inheritance
1.Y-linked (holandric) traits, except for
maleness itself (resulting from SRY on the Y
chromosome), have not been confirmed.
2.The hairy ears trait may be Y-linked, but it is a
complex phenotype, and might also be the
result of autosomal gene(s) and/or effects of
testosterone.
台大農藝系 遺傳學 601 20000
Chapter 11 slide 75