Essentials of Genetics

Tenth Edition

Chapter 5
Sex Determination and
Sex Chromosomes

Copyright © 2020, 2016, 2012 Pearson Education, Inc. All Rights Reserved
 Introduction
• Wide range of reproductive modes and life cycles in biological world:
• Some organisms are entirely asexual.
• Some alternate between short periods of sexual reproduction and prolonged
periods of asexual reproduction.

• Sexual differentiation:
• Successful fertilization depends on sexual differentiation in reproductive
organisms.
• In complex life forms, differentiation of sexes is more evident as phenotypic
dimorphism of males and females.

• Heteromorphic chromosomes (XY in mammals) characterize one sex or the other

in a wide range of species:
• Labeled as sex chromosomes.
• Genes, not chromosomes, ultimately serve as basis for sex determination.
5.1 X and Y Chromosomes Were
First Linked to Sex Determination
Early in the Twentieth Century
X and Y Chromosomes
• Nuclear structure in sperm of insect discovered in 1891—
labeled X-body:
• In butterfly (Protenor):
• Female somatic cells have 14 chromosomes,
including two X chromosomes.
• Male somatic cells have 13 chromosomes with
one X chromosome:

• Fertilization by X-bearing sperm → female offspring

– Fertilization by X-deficient sperm → male offspring
Protenor and Lygaeus Insects
• Protenor and Lygaeus insects:
• Males produce unlike gametes (heterogametic sex).
Their gametes determine the sex of progeny.
• Female produce like gametes (homogametic sex)—
uniform gametes.
• In some organisms, females produce unlike gametes:
• Protenor XX/XO or Lygaeus XX/XY mode of sex
determination.
• See Figure 5.1.
Figure 5.1
(a) Sex determination where
the heterogametic sex (the
male in this example) is X0
and produces gametes with or
without the X chromosome; (b)
sex determination, where the
heterogametic sex (again, the
male in this example) is XY
and produces gametes with
either an X or a Y
chromosome. In both cases,
the chromosome composition
of the offspring determines its
sex.
5.2 The Y Chromosome Determines
Maleness in Humans
The Human Karyotype
• Human karyotype revealed one pair of chromosomes
differs in males and females:
• Metaphase stages showed 46 was human diploid
number.
• Of the 23 pair chromosomes, one pair is varied in
configuration in males and females:
• Females have two X chromosomes (XX).
• Males have one X chromosome and one Y
chromosome (XY):
• Y chromosome determined maleness in humans.
Klinefelter Syndrome

• Klinefelter syndrome:
• Individuals have more than one X chromosome:
• Often an XXY complement in addition to 44
autosomes (47,XXY karyotype) Figure 5.2(a).
• Tall with long arms and legs—large hands and feet.
• Testes are rudimentary—fail to produce sperm.
• Slight breast enlargement and hips often rounded.
Turner Syndrome
• Turner syndrome:
• Individuals often have 45 chromosomes with a single X
chromosome (45,X karyotype) Figure 5.2(b).
• Female external genitalia and internal ducts but
ovaries rudimentary.
• Short stature, skin flaps on back of neck,
underdeveloped breasts, broad shield-like chest.
• Normal intelligence.
Klinefelter and Turner Syndromes

• Both Klinefelter and Turner syndromes occur due to

nondisjunction during meiosis:
• Failure of sex chromosomes to segregate during
meiosis.
• Y Chromosome in Klinefelter and Turner syndrome:
• Klinefelter: Y chromosome is sufficient to determine
maleness.
• Turner: Absence of Y chromosome—no
masculinization occurs:
• Turner syndrome has karyotypes other than 45,X.
• Mosaics: Somatic cells display two different
genetic cell lines with different karyotypes.
Figure 5.2
The karyotypes of individuals with (a) Klinefelter syndrome
(47,XXY) and (b) Turner syndrome (45,X).
Karyotype 47,XXX Syndrome (Triplo-X)

• Triplo-XXX:
• Three X chromosomes along with normal set of
autosomes (47,XXX).
• Results in female differentiation (1/1000 live births).
• Often 47,XXX women perfectly normal—unaware of
condition.
• Underdeveloped secondary sex characteristics,
sterility, intellectual disability do occur.
• Tetra-X (48,XXXX) and penta-X (49,XXXXX) karyotypes
have been reported.
Karyotype 47,XYY Condition
• 47,XYY:
• Presence of additional Y chromosome is only
deviation from diploidy.
• Consistently shared characteristic found so far:
• Males are over 6 feet tall.
• May have subnormal intelligence.
• May have personality disorders.
Sexual Differentiation in Humans (1 of 2)
• Y chromosome houses genetic information for
maleness—gene provides “signal:”
• In early embryonic development human embryo
hermaphroditic—gonadal phenotype sexually
indifferent.
• By 5th week, gonadal ridges form either ovaries or
testes (bipotential gonads).
Sexual Differentiation in Humans (2 of 2)
• Y chromosome houses genetic information for
maleness—gene provides “signal:”
• If cell of ridge has XY constitution → medulla
develops into testes.
• Absence of Y chromosome:
• Cortex of ridge forms ovarian tissue.
• Mullerian duct forms oviducts (Fallopian tubes),
uterus, cervix, and portions of vagina.
The Y Chromosome and Male Development

• Y chromosome has far fewer genes than X:

• Y chromosome has at least 75 genes.
• X chromosome has 900–1400 genes.
• Pseudoautosomal regions (PARs):
• Present on both ends of Y chromosome—share
homology with regions on X chromosome.
• Synapse and recombine with X chromosome during
meiosis.
• Pairing region critical for segregation of X and Y
chromosomes during male gametogenesis.
Male-Specific Region of Y (MSY)
• MSY: Male-specific region of Y:
• 95% of Y chromosome which does not recombine with
X chromosome.
• Some portions share homology with genes on X
chromosome.
• SRY: Sex-determining region Y:
• Critical gene controlling sexual development.
• Gene becomes active in XY embryos at 6–8 weeks
of development.
• Figure 5.3
Figure 5.3 The regions of the human Y chromosome.
Testis-Determining Factor (TDF)
• SRY gene encodes protein TDF:
• Present in all mammals—triggers testes formation.
• Causes undifferentiated gonadal tissue of embryo to
form testes.
• Deviations from normal sex determination:
• Males with two X chromosomes and no Y.
• Females with one X chromosome and one Y
chromosome are missing SRY gene.
Transgenic Mice Research
• Transgenic mice research:
• Produced from fertilized eggs injected with foreign DNA.
• Mice have Sry gene comparable to human SRY.

• Mouse DNA with Sry injected into XX mice eggs →

most offspring being males.
• TDF believed to be transcription factor:
• Behaves as master switch controlling genes involved
in sexual differentiation.
 5.3 The Ratio of Males to Females
in Humans Is Not 1:1 1 point 01:1

Human Sex Ratio

• Sex ratio:
• Proportion of male to female offspring assessed in two
ways:
• Primary and secondary sex ratios.
• Primary sex ratio:
• Reflects proportion of males to females conceived in
population.
• Secondary sex ratio:
• Reflects proportion of each sex born:
• Does not account for fetal mortality.
Sex Ratio—Male to Female Ratio
• Why are more males born than females?
• Due to segregation, males produce equal numbers of
X- and Y-bearing sperm.
• Each type of sperm has equivalent viability and motility
in female reproductive tract.
• Egg surface is receptive to both X- and Y-bearing
sperm.
• Question is still under investigation; recent findings
contradict and convince earlier studies.
5.4 Dosage Compensation Prevents
Excessive Expression of X-Linked
Genes in Humans and Other
Mammals
Dosage Compensation
• Dosage compensation:
• Females have potential to produce twice as much
product for X-linked genes:
• May create a “genetic dosage” difference
between genders.
• X-linked gene expression demonstrates genetic
mechanism for dosage compensation.
• Balances dose of X chromosome gene expression in
males and females.
Barr Bodies
• Barr Bodies (Sex chromatin body) Figure 5.4:
• Genetic mechanism in mammals compensates for X
chromosome dosage disparities.
• Inactive X chromosomes—highly condensed (sex
chromatin or Barr body):
• Lies against nuclear envelope of interphase cells.
• Arise from one of two X chromosomes.
• Provide possible mechanism for dosage
compensation.
Figure 5.4 Photomicrographs comparing cheek epithelial cell nuclei from a
male that fails to reveal Barr bodies (right) with a nucleus from a
female that demonstrates a Barr body (indicated by the arrow in
the left image). This structure, also called a sex chromatin body,
represents an inactivated X chromosome.
X-Inactivation
• If one of two X chromosomes is inactivated:
• Why is Turner syndrome 45,XO not entirely normal?
• Why are females with triple or tetra Xs not normal?
• Why does an extra X in Klinefelter syndrome (47,XXY)
result in a characteristic phenotype?
• Possible explanations:
• Inactivation does not take place in the early stages of
gonadal tissue development.
• Not all genes on X chromosomes are inactivated.
• Figure 5.5
Figure 5.5

Occurrence of Barr
bodies in various
human karyotypes,
where all X
chromosomes except
one (N−1) are
inactivated.
The Lyon Hypothesis
• Lyon hypothesis:
• Inactivation of X chromosome is random; all
descendant cells have same inactivation.
• Research on mice heterozygous for X-linked coat color
genes:
• Heterozygote female mice show mottling coat color
for coat-color genes on X chromosome.
• Calico cats show black and yellow-orange patches of
fur color (Figure 5.6).
Figure 5.6 (a) The random distribution of orange and black patches in a
calico cat illustrates the Lyon hypothesis. The white patches
are due to another gene, distinguishing calico cats from
tortoiseshell cats (b), which lack the white patches.
Lyon Hypothesis Study

• Direct evidence supports the Lyon hypothesis:

• Studies of direct gene expression in clones of human
fibroblast cells:
• Clones are a culture of cells derived from a single
cell.
• Study showed X inactivation in clone cells.
• Human G6PD (glucose 6-phosphate dehydrogenase):
• Controlled by X-linked gene.
• Fibroblasts from heterozygous females studied for
different allelic forms of G6PD.
The remaining slides in Chapter 5 are
for your reference only (this material
will not be tested).
Mechanism of Inactivation
• X-Inactivation:
• DNA, histone proteins, or both are chemically
modified.
• DNA inactivated—silences most genes.
• Creates memory that keeps same homolog
inactivated following chromosome replications and
cell division.
• Imprinting:
• Process whereby expression of genes on one
homolog but the other is not affected.
Xic: Mechanism of Inactivation
• X-inactivation center (Xic):
• Located on proximal end of p arm in humans.
• Major control unit on X chromosome.
• Genetic expression occurs only on inactivated X
chromosome.
• Consists of X-inactive specific transcript (XIST)
gene—critical to inactivation.
5.5 The Ratio of X Chromosomes to Sets of
Autosomes Can Determine Sex

Drosophila and C. Elegans (1 of 2)

• Drosophila have same sex chromosomes as humans:
• Female XX and male XY.
• However, Y chromosome does not determine sex in
Drosophila and Caenorhabditis elegans (C.
elegans).
• Drosophila: Contains Y chromosome, but has no role.
• C. elegans: Has no Y chromosome.
Drosophila and C. Elegans (2 of 2)
• Sex is determined by ratio of X chromosomes to haploid
sets of autosomes (A):

Normal female AA and XX 1∶1

Normal male AA and XY 1∶2

• Figure 5.7 shows correlation between sexual morphology

and chromosome composition.
• X chromosome on male (in Drosophila):
• Upregulated transcription level equals XX female.
Figure 5.7 The ratios of X chromosomes to sets of autosomes and the resultant
sexual morphology seen in Drosophila melanogaster.

Ratio of X
Chromosome chromosomes Sexual
Formulation to autosome morphology
sets
3X∶2A 1.5 Metafemale
3X∶3A 1.0
1 point 0

Female
2X∶2A 1.0
1 point 0

Female
3X∶4A 0.75 Intersex
2X∶3A 0.67 Intersex
X∶2A 0.50 Male
XY∶2A 0.50 Male
XY∶3A 0.33 Metamale
Genetic Balance Theory
• Genetic balance theory:
• Threshold of maleness is reached when X∶A ratio is
1∶2 (X∶2A).
• Presence of additional X (XX∶2A) alters balance and
results in female differentiation.
Two Phenotypes of C. Elegans

• C. elegans has two sexual phenotypes:

• Males with one testes have only one X chromosome,
no Y.
• Hermaphrodites (have both testes and ovaries):
• Have two X chromosomes, no Y.
• Eggs are fertilized by stored sperm–self-
fertilization.
• Majority of offspring are hermaphrodites; less than 1%
are males.
• See Figure 5.8.
Figure 5.8
(a) Photomicrograph of a
hermaphroditic
nematode, C. elegans;
(b) the outcomes of self-
fertilization in a
hermaphrodite, and a
mating of a
hermaphrodite and a
male worm.
5.6 Temperature Variation Controls Sex
Determination in Reptiles

• TSD: Temperature-dependent sex determination:

• Environment, specifically temperature, has profound
influence on sex determination.
• Reptile species use ZZ/ZW or XX/XY in sex
determination; in others TSD is the norm.
• Enzymes involved in steroids, androgens, and estrogen
synthesis are affected (inhibited) by temperature.
Patterns of Temperature Sex
Determination
• Three different patterns of temperature sex determination
in reptiles (Figure 5.9):
• Case I : Low temperatures yield 100% females; high
temperatures yield 100% males.
• Case II : Exact opposite occurs.
• Case III : Low and high temperatures yield 100%
females; intermediate temperatures yield various
proportions of males:
• Seen in various species of crocodiles, turtles, and
lizards.
Figure 5.9 Three different patterns of temperature-dependent sex
determination (TSD) in reptiles, as described in the text. The
relative pivotal temperature Tp is crucial to sex determination
during a critical point during embryonic development. FT =
Female-determining temperature; MT = male-determining
temperature
Aromatase
• Temperature effects on enzymes:
• Aromatase converts androgens (male hormones such
as testosterone) to estrogens (female hormones such
as estradiol).
• Thermosensitive factors mediate transcription of
gene.
• Sex-determining mechanisms involving estrogens are
characteristic of nonmammalian vertebrates.