Bismarck John Z.

Salazar *There is a wide variation of sex-

B.S. Biology 2-6 chromosome systems, suggesting that
sex-determining mechanisms
Genetics Lecture undergone rapid evolution

Chapter Summary: 5.1 X and Y chromosomes were first

linked to sex determinationin the 20th
Sex Determination And Sex
century
Chromosomes
Herman Henking
FISH method
-Henking identified the nuclear structure in
-fluorescence in-situ hybridization
the sperm of certain insects which he
-A method in which specific labeled,”X-body”,several years later
probes,specially fluorescent dyes,are used
to determine specific sequences of DNA
Clarence McClung
Sexual Differentiation
-McClung showed that some of the sperm in
-A process that determines whether an
grasshoppers contain an unusual genetic
organism is a male,female or a
structure called heterochromosome,but
hermaphrodite(both male and female).
the remainder of the sperm lacks this
-It is the key to successful fertilization,which structure
produces viable offsprings.
-He mistakenly associated the presence of
-It is more evident in more complex heterochromosome with the production of
organisms as male or female dimorphism male progeny
than in lower forms such as bacteria and
Edmund B.Wilson
alga .
-Wilson clarified Henking’s and McClung’s
Sex chromosomes
findings when he demonstrated that female
-These are chromosomes that are different somatic cells in the butterfly genus Protenor
in males and females. contain 14 chromosomes

-Sex chromosomes contain genes which -During oogenesis,an even reduction occurs
serve as basis for sex determination producing gametes with seven
chromosomes that includes one X-
-Sex chromosomes are designated as the chromosome
23rd pair ,which may be XX(female) and
XY(male),in humans -During spermatogenesis,gametes are
produced containing either six
Autosomal Chromosomes chromosomes,without an X chromosome or
Seven chromosomes including one X
-All other chromosomes in a cell except the
chromosome
sex chromosomes
-Fertilization by X-bearing sperm results in a offspring determines its sex
female offspring

-Fertilization by X-deficient sperm results in

male offspring

-Figure A shows that Sex determination

where the heterogametic sex (the male in
this example) is XO and produces gametes
with or without the X chromosome

Heterogametic sex

-It is the sex(male or female) that produces

unlike gametes.In Protenor and Lygaeus
spp ,it is the male which is the
heterogametic sex. In effect, it is the
gametes of heterogametic sex that
ultimately determines the sex of the progeny
-.Wilson also experimented with the in those species.
milkweed bug Lygaeus turcicus, in which
both sexes have 14 chromosomes. Twelve Homogametic sex
of these are autosomes (A). In addition, the
-It is the sex(male or female ) producing
females have two X chromosomes, while
uniform gametes with regard to
the males have only a single X and a
chromosome numbers and types. In
smaller heterochromosome labeled the Y
Protenor and Lygaeus spp ,it is the female
chromosome. Females in this species
which is the homogametic sex
produce only gametes of the (6A + X)
constitution, but males produce two types of The male is not always the
gametes in equal proportions, (6A + X) and heterogametic sex. In some
(6A + Y). Therefore, following random organisms, the female produces
fertilization, equal numbers of male and unlike gametes, exhibiting either
female progeny will be produced with the Protenor XX/XO or Lygaeus
distinct chromosome complements XX/XY mode of sex determination
Figure B shows sex determination, where ZZ/ZW notation
the heterogametic sex (again, the male in
this example) is XY and produces gametes -This is a notation used to immediately
with either an X or a Y chromosome. In both distinguish situations in which the female is
cases, the chromosome composition of the the heterogametic sex, some geneticists
use the notation ZZ/ZW, where ZZ is the
homogametic male and ZW is the
heterogametic female, instead of the XX/XY
notation. For example, chickens are so
denoted.
5.2 The Y Chromosome Determines -feminine sexual development is not entirely
Maleness in Humans suppressed.

Joe Hin Tjio and Albert Levan(1956) -Slight enlargement of the breasts
(gynecomastia) is common
-They discovered an effective way to
prepare chromosomes for -rounded hips (female characteristic)
accurate viewing which is called a -mixture of male and female traits called
karyotype intersexuality that can lead to abnormal
social development
-The karyotype proved that there are 46
chromosomes in a human cell during the -below normal rang intelligence
metaphase stage
Turner’s syndrome
E.Ford and John L.Hamerton
-Has 45 chromosomes in total but only one
-Later after the discovery of karyotype, Ford X chromosome in the 23rd pair(45,X)
and Hamerton, researchers of testiscular
-the affected individual has female external
tissue,confirmed Tjio’s and Levan’s findings
genitalia and internal ducts, but the ovaries
*The following variation in the 23rd pair of are rudimentary.
chromosomes proves that the Y
-short stature (usually under 5 feet)
chromosome really determines maleness in
humans -skin flaps on the back

Klinefelter’s and Turner’s Syndrome of the neck

Around 1940, scientists identified two -underdeveloped breasts.

human abnormalities characterized by
aberrant sexual development, Klinefelter -A broad, shieldlike chest is sometimes
syndrome (47,XXY) and Turner syndrome noted.
(45,X).* which are caused by nondisjunction
-normal intelligence
of chromosomes during anaphase.
*Klinefelter’s and Turner’s syndromes
Klinefelter syndrome
helped scientists prove that the human y
-Individuals have 47 chromosomes where chromosome determines maleness.
the 23rd pair is made of 2 X,and 1
*The presence of the Y chromosome in the
Y(47,XXY)
individual with Klinefelter syndrome is
-Individuals with Klinefelter’s syndrome are sufficient to determine maleness, even
generally tall and have long arms and legs though male development is not complete.
and large hands and feet. Similarly, in the absence of a Y
chromosome, as in the case of individuals
-They usually have genitalia and internal with Turner syndrome, no masculinization
ducts that are male, but their testes are occurs.
rudimentary and fail to produce sperm.
*Y-containing human embryos lacking an X -results in female differentiation
chromosome (designated 45,Y) do not
survive. -Have the same effects as triplo-X
syndrome ,but more pronounced
*The karyotypes (48,XXXY),( 48,XXYY),
(49,XXXXY), and( 49,XXXYY) are similar - the presence of additional X chromosomes
phenotypically to (47,XXY), but appears to disrupt the delicate balance of
manifestations are often more severe in genetic information essential to normal
individuals with a greater number of X female development.
chromosomes. XYY Condition
*Turner syndrome can also result from -Studied by Patricia Jacobs in 1965
karyotypes other than (45,X), including
individuals called mosaics, whose somatic - She discovered that 9 of 315 males in a
cells display two different genetic cell lines,
Scottish maximum security prison had the
each exhibiting a different karyotype. Such
cell lines result (47,XYY) karyotype.
from a mitotic error during early
development, the most common -These imprisoned (47,XYY) males were
chromosome combinations being (45,X) , significantly above average in height and
(46,XY) had been imprisoned as a result of
and( 45,X) ,( 46,XX). Thus, an embryo that dangerous, violent, or criminal propensities.
began life with a Of the nine males studied, seven were of
normal karyotype can give rise to an subnormal intelligence, and all suffered
individual whose cells
personality disorders. Several other studies
show a mixture of karyotypes and who
exhibits varying produced similar findings.
aspects of this syndrome.
- Above-average height(usually over 6 feet)
(47,XXX) Syndrome/triplo-X syndrome and subnormal intelligence were
substantiated, and the frequency of males
-The abnormal presence of three X displaying this karyotype was indeed
chromosomes along with a normal set of revealed to be higher in penal and mental
autosomes (47,XXX) results in female institutions compared with unincarcerated
differentiation. populations

- triplo-X women are perfectly normal and - it has became clear that there are many
may remain unaware of their abnormality in XYY males present in the population who
chromosome number unless a karyotype is do not exhibit antisocial behavior and who
conducted. lead normal lives. Therefore, we must
conclude that there is a high, but not
- In other cases, underdeveloped secondary
constant, correlation between the extra Y
sex characteristics, sterility, delayed chromosome and the predisposition of
development of language and motor skills, these males to exhibit behavioral problems.
and mental retardation may occur.
Sexual Differentitation in Humans
48,XXXX(tetra-X
syndrome),49,XXXXX(penta-X syndrome)
-Scientists and researchers attempted to - The cortex is capable of developing into
pinpoint a specific gene or genes capable of an ovary, while the medulla may develop
providing the “signal” responsible for sex into a testis.
determination
- two sets of undifferentiated ducts called
-During early development, every human the Wolffian and Müllerian ducts exist in
embryo undergoes a period when it is each embryo.
potentially hermaphroditic.
-Wolffian ducts differentiate into other
By the fifth week of gestation, gonadal organs of the male reproductive tract,
primordia (the tissues that will form the
gonad) arise as a pair of gonadal (genital) - Müllerian ducts differentiate into
ridges associated with each embryonic structures of the female reproductive
kidney. At this stage male or female tract.
reproductive structures cannot be
-Gonadal ridges are commonly referred to
distinguished, and the gonadal ridge as bipotential gonads,because they can
tissue can develop to form male or form either ovaries or testes,
female gonads.
-The presence or absence of a Y
chromosome triggers gonadal ridge’s
development into testes or ovaries.

-If cells of the ridge have an XY

constitution, development of the medulla
into a testis is initiated around the seventh
week.

-In the absence of the Y chromosome ,the

cortex of the ridge subsequently forms
ovarian tissue, and the Müllerian duct forms
oviducts (Fallopian tubes), uterus,
cervix, and portions of the vagina.

Depending on which pathway is initiated,

parallel development of the appropriate
male or female duct system then occurs,
and the other duct system degenerates.
-As development progresses, primordial
germ cells migrate to these ridges, where As we will discuss in the next section, the
an the cortex and the medulla form presence of a Y chromosome and the
development of the testes also inhibit
*note: formation of female reproductive organs. In
cortex-outer organ tissue;medulla-inner females, as the twelfth week of fetal
organ tissue development approaches, the oogonia
within the ovaries begin meiosis, and
primary oocytes can be detected. By the
twenty-fifth week of gestation, all oocytes
become arrested in meiosis and remain
dormant until puberty is reached some 10 to
15 years later. In males, on the other hand,
primary spermatocytes are not produced
until puberty is reached .

If testes differentiation is initiated, the

embryonic testicular tissue secretes
hormones that are essential for continued
male sexual differentiation.
The Y Chromosome and Male .
Development

-The Y chromosome was long thought as

having no bearing on the genotype of a

human being.This is now disproved

because it was discovered that it contains
75 genes ,compared to the X
chromosomes which contain 900 -1400
genes.

Homologous regions on X and Y

chromosomes

-It is now known through current analysis

that the X and Y chromosomes have
homologous counterparts Male-specific region of the Y
chromosome(MSY)
-An example of homologous regions to both
X and Y chromosomes are the X’s and Y’s -The MSY is divided about equally between
pseudoautosomal regions(PARs) which euchromatic regions and heterochromatic
synapse and recombine during meiosis. regions.

-The presence of homologous pairing -Euchromomatic regions of the MSY contain

regions are critical to segregation of the X functional genes.
and Y chromosomes during male
-Heterochromatic regions of the Y
gametogenesis
chromosomes lack genes.
Non recombining regions on Y
-The sex –determining region of the Y
chromosome
chromosome(SRY) is a critical gene that
-95 percent of the regions on the Y controls male sexual development located
chromosome does not synapse or within the euchrromatin adjacent to the
recombine with the X pseudoautosomal region of the short arm of
chromomosome.These regions were the Y chromosome
previously named as the nonrecombining
-The SRY gene is absent in the X
region of the Y chromosome(NRY).More
chromosome ,thus the absence of a Y
recently the NRY region has been
chromosome almost always leads to female
designated as the male specific region of
development in humans
the Y chromosome(MSY).
.-At six to eight weeks of development, the
--Some portions of the MSY are
SRY gene becomes active in XY embryos.
homologous with genes on the X
chromosome -The SRY encodes a protein that causes
the undifferentiated gonadal tissue of the
embryo to form testes. This protein is called -Maternal age is correlated with an elevated
the testis-determining factor (TDF). rate of offspring with chromosomal defects,
including Down syndrome
-SRY (or a closely related version) is
present in all mammals thus far examined, -Advanced paternal age has now been
indicative of its essential function throughout associated with an increased risk in
this diverse group of animals. offspring of congenital disorders with a
genetic basis, including certain cancers,
-Modern DNA and chromosomal analysis schizophrenia, autism, and other
proves that the SRY gene is really the gene conditions,collectively known as paternal
responsible for providing primary signal for age effects (PAE).
male development.
Studies in which the genomes of sperm
-Human males who have two X have been sequenced have demonstrated
chromosomes and no Y chromosomes are the presence of specific PAE mutations,
discovered to have the SRY gene attached including numerous ones on the Y
to one of the X chromosome.The. Females chromosome. Evidence suggests that PAE
who have one X and one Y chromosomes mutations are positively selected for and
are discovered to have Y chromosomes result in an enrichment of mutant sperm
missing the SRY gene. These observations over time.
argue strongly in favor of the role of SRY in
providing the primary signal for male 5.3 The Ratio of Males to Females in
development. Humans Is Not 1.0

-Normal XX mouse egg cells injected with -Since half of the male gametes contain half
the mouse chromosomal region analogous X or Z chromosome,and the other half
to the human SRY region developed into contains Y or W chromosomes,It is
males further supporting that the SRY gene expected that there is 1:1 sex ratio.This
is responsible for spermatozoa would then fertilize an egg and
undergo meiosis which will result into a
- Testis-determining factor(TDF) is now male or female offspring.This means that
believed to function as a transcription factor. the probability of having a male and a
female offspring are expected to be
*note*
equal.Observations and experiments
Transcription factor- a DNA binding protein regarding number of male or female births,
that interacts directly with the regulatory and in-vitro fertilization show that the
sequences of other genes to stimulate their
primary sex ratio-the ratio of male or female
expression.
offspring upon the prenatal period is 1:1
-Thus, TDF behaves as a master switch that .However,
controls other genes in the process of
female mortality or deaths is greater than
sexual differentiation.
male mortality resulting in a secondary sex
-many transcription factor identified thus far ratio,which males are greater females
reside on autosomes, including the human (M>1:F=1)
SOX9 gene located on chromosome 17.
secondary sex ratio-the sex ratio at birth or Klinefelter (47,XXY) males; two in (47,XXX)
the ratio of male to female born. females; three in( 48,XXXX) females; and
so on . Therefore, the
Barr Bodies
-Number of Barr bodies = N − 1, where N is
-Murray L Barr and Ewart G.Bertram the total number of X chromosomes present
observed darkly stained body using a DNA- in a female somatic cell.
staining dye in the interphase nerve cells of
female cats that was absent in similar male
cells. .

-In humans, this body can be easily

demonstrated in female cells derived from
the buccal mucosa (cheek cells) or in
fibroblasts (undifferentiated connective
tissue cells), but not in similar male cells
.This chromosome structure, called a sex -Although this apparent inactivation of all
chromatin body, or simply a Barr body, is an but one X chromosome increases our
inactivated X chromosome. understanding of dosage compensation, it
further complicates our perception ofother
-Susumo Ohno was first to suggest that the matters. For example, because one of the
Barr body results from one of the two X two X chromosomes is inactivated in normal
chromosomes. This hypothesis is human females, why then is the Turner 45,X
interesting because it may be an example individual not entirely normal? Why aren’t
of dosage compensation. If one of the two females with the triplo-X and tetra-X
X chromosomes is inactive in the cells of karyotypes (47,XXX and 48,XXXX)
females, the dosage of genetic information completely unaffected by the additional X
that can be expressed in males and females chromosome? Furthermore, in Klinefelter
will be equivalent since both XX and XY will syndrome (47,XXY), X chromosome
have only have one set of X-linked traits inactivation effectively renders the person
expressed in one X chromosome(the other 46,XY.
is inactivated and degrade into the barr
body or sex chromatin body thus it has a -chromosome inactivation does not normally
lesser chance of being transcribed into an occur in the very early stages of
RNA). development of pre-gonadal tissue cells
Another possible explanation is that not all
-evidence for the X inactivation comes from genes on each X chromosome forming a
study of the sex chromosome syndromes Barr body are inactivated.
described earlier in this chapter.
-15 % of the human X chromosomal genes
-Regardless of how many X chromosomes actually escape inactivation. Clearly, then,
a female somatic cell possesses, all are not every gene on the X requires
inactivated into a barr body except one X inactivation. In either case, excessive
chromosome Barr bodies. For example, no expression of certain X-linked genes might
Barr body is seen in the somatic cells of still occur at critical times during
Turner( 45,X) females; one is seen in
development despite apparent inactivation fibroblast cells. Individual cells are
of superfluous X chromosomes. isolatedfollowing biopsy and cultured in
vitro. A culture of cells derived from a single
The Lyon Hypothesis cell is called a clone.
-In the early 1960s, Mary Lyon, Liane -The synthesis of the enzyme glucose-6-
Russell, and Ernest Beutler independently phosphate dehydrogenase (G6PD) is
postulated that the inactivation of X controlled by an X-linked gene.
chromosomes occurs randomly in somatic
cells at a point early in embryonic - Numerous mutant alleles of this gene have
development, most likely sometime during been detected, and their gene products can
the blastocyst stage of development. be differentiated from the wild-type enzyme
by their migration pattern in an
-Once inactivation has occurred, all electrophoretic field.
descendant cells have the same X
chromosome inactivated as their initial - Fibroblasts have been taken from females
progenitor cell. This explanation, which has heterozygous for different allelic forms of
come to be called the Lyon hypothesis G6PD and studied.

-.The pigmentation of Female mice - The Lyon hypothesis predicts that if

heterozygous for X-linked coat-color genes inactivation of an X chromosome occurs
was mottled with large patches expressing randomly early in development, and
the color allele on one X and other patches thereafter all progeny cells have the same X
expressing the allele on the other X.This is chromosome inactivated as their progenitor,
the phenotypic pattern that would be such a female should show two types of
expected if different X chromosomes were clones, each containing only one
inactive in adjacent patches of cells. Similar electrophoretic form of G6PD, in
mosaic patterns occur in the black and approximately equal proportions. This
yellow-orange patches of female prediction has been confirmed
tortoiseshell and calico experimentally, and studies involving
modern techniques in molecular biology
have clearly established that X chromosome
inactivation occurs.

-One ramification of X-inactivation is that

mammalian females are mosaics for all
heterozygous X-linked alleles— some areas
.-Such X-linked coat-color patterns do not of the body express only the maternally
occur in male cats because all their cells derived alleles, and others express only the
contain the single maternal X chromosome paternally derived alleles.
and are therefore hemizygous for only one
-An especially interesting example involves
X-linked coat-color allele.
red– green color blindness, an X-linked
The most direct evidence in support of the recessive disorder.
Lyon hypothesis comes from studies of
gene expression in clones of human
-In humans, hemizygous males are fully - One of these, X-inactive specific transcript
color-blind in all retinal cells. However, (XIST), is now known to be a critical gene
heterozygous females display mosaic for X-inactivation.
retinas, with patches of defective color
perception and surrounding areas with -First, the RNA transcribed from XIST is
normal color perception. In this quite large and does not encode a protein,
example,random inactivation of one or the and thus is not translated discovered
other X chromosome early in the through from experiments that used the
development of heterozygous females has equivalent gene in the mouse (Xist).
led to these phenotypes. - The RNA products of Xist spread over and
The Mechanism of Inactivation coat the X chromosome bearing the gene
that produced them.
-Scientists hypothesized that either DNA,
the attached histone proteins, or both DNA -Two other noncoding genes at the Xic
and histone proteins, are chemically locus, Tsix (an antisense partner of Xist)
modified, silencing most genes that are part and Xite, are also believed to play important
of that chromosome. roles in X-inactivation.

-Once silenced, a memory is created that -A second observation is that transcription

keeps the same homolog inactivated of Xist initially occurs at low levels on all X
following chromosome replications and cell chromosomes.
divisions. Such a process, whereby -As the inactivation process begins,
expression of genes on one homolog, but however, transcription continues, and is
not the other, is affected, is referred to as enhanced, only on the X chromosome that
imprinting. becomes inactivated.
-Imprinting also applies to a number of other - In 1996, a research group led by Neil
examples in which genetic information is Brockdorff and Graeme Penny provided
modified and gene expression is repressed. convincing evidence that transcription of
Collectively, such events are part of the Xist is the critical event in chromosome
growing field of epigenetics. inactivation. These researchers introduced
- the X inactivation center (Xic) is a region of a targeted deletion (7 kb) into this gene,
the mammalian X chromosome that is the disrupting its sequence. As a result, the
major control unit which is located on the chromosome bearing the deletion lost its
proximal end of the p arm in humans. ability to become inactivated.

-The genetic expression of Xic occurs only 5.5 The Ratio of X Chromosomes to Sets
on the X chromosome that is inactivated. of Autosomes Can Determine Sex

-The Xic is about 1 Mb (10 6 base pairs) in -There are cases when the Y chromosome
length and is known to contain several does not play a role in sex determination.
putative regulatory units and four genes. An example is the fruit fly, Drosophila
melanogaster.Even though most males
contain a Y chromosome, the Y plays no
role. Second, in the roundworm,
Caenorhabditis elegans, the organism lacks -Fertilization of gametes with nondisjuncted
a Y chromosome altogether. In both cases, chromosomes with a haploid gamete
we shall see that the critical factor is the produces (2n + 1) or (2n - 1) zygotes. As in
ratio of X chromosomes to the numbersof humans, if nondisjunction involves the X
sets of autosomes. chromosome, in addition to the normal
complement of autosomes, both an XXY
Drosophila melanogaster and an X0 (no additional x or y)sex-
chromosome composition may result.
-Males and females in the genus Drosophila
Contrary to what was later discovered in
have the same generalsex-chromosome
humans,
composition as humans (males are XY and
females are XX), we might assume that the -Bridges found that the XXY flies were
Y chromosome also causes maleness in normal females and the X0 flies were sterile
these flies. males.
Calvin Bridges -The presence of the Y chromosome in the
XXY flies did not cause maleness, and its
-The studies of Calvin Bridges in 1921
absence in the X0 flies did not produce
showed showed varied chromosome
femaleness.
composition leading him to conclude the Y
chromosome is not involved in sex -Bridges concluded afterwards that the Y
determination chromosome in Drosophila lacks male-
determining factors, but since the X0 males
. -Instead, Bridges proposed that the X
were sterile, it does contain genetic
chromosomes and autosomes together play
information essential to male fertility.
a critical role in sex determination.
-Bridges was able to clarify the mode of sex
-Bridges’ work is divded into two phases:
determinationin Drosophila by studying the
(1) A study of offspring resulting from progeny of triploid females (3n), which have
nondisjunction of the X chromosomes three copies each of the haploid
during meiosis in females and complement of chromosomes. Drosophila
has a haploid number of 4,(3 autosomes
(2) Subsequent work with progeny of and 1 sex chromosome)
females containing three copies of each
chromosome, called triploid (3n) females. -Triploid females apparently originate from
rare diploid eggs fertilized by normal haploid
-Nondisjunction is the failure of paired sperm.
chromosomes to segregate or separate
during the anaphase stage of the first or -Triploid females have heavy-set bodies,
second meiotic divisions. The result is the coarse bristles, and coarse eyes, and they
production of two types of abnormal may be fertile.
gametes, one of which contains an extra
-Because of the odd number of each
chromosome (n + 1) and the other of which
chromosome (3), during meiosis, a variety
lacks a chromosome (n - 1).
of different chromosome complements are
distributed into gametes that give rise to
offspring with a variety of abnormal -Male gametes containing one of each
chromosome constitutions. Correlations autosome plus a Y chromosome result in
between the sexual morphology and male offspring not because of the presence
chromosome composition, along with of the Y but because they fail to contribute
Bridges’ interpretation, are shown in this an X chromosome.
table
-This mode of sex determination is
explained by the genic balance theory.
Bridges proposed that a threshold for
maleness is reached when the X:A ratio is
1:2 (X:2A), but that the presence of an
additional X (XX:2A) alters the balance and
results in female differentiation.

-Numerous genes involved in sex

determination in Drosophila have been
identified.

H. Sturtevant

-The recessive autosomal gene transformer

(tra), discovered by Alfred H. Sturtevant,
clearly demonstrated that a single
autosomal gene could have a profound
impact on sex determination.

-Females homozygous for tra are

transformed into sterile males, but
homozygous males are unaffected.

-Sex-lethal (Sxl), has been shown to play a

critical role, serving as a “master switch” in
-Bridges realized that the critical factor in sex determination.
determining sex is the ratio of sets of X
chromosomes to the number of set of -Activation of the X-linked Sxl gene, which
haploid sets of autosomes (A) present. relies on a ratio of X chromosomes to sets
of autosomes that equals 1.0, is essential to
-Factors that cause a fly to develop into a female development.
male are not located on the sex
chromosomes but are instead found on the -In the absence of activation,male
autosomes according to Bridges development occurs.An example of this is
when the ratio of sex to autosomal
-Some female-determining factors, chromosomes is X:A (0.5)
however, are located on the X
chromosomes. -Although it is not yet exactly clear how this
ratio influences the Sxl locus, we do have
some insights into the question.
-The Sxl locus is part of a hierarchy of gene
expression and exerts control over other
genes, including tra and dsx (doublesex).

-The wild-type allele of tra is activated by

the product of Sxl only in females and in
turn influences the expression of dsx.

-Depending on how the initial RNA

transcript of dsx is processed, the resultant
dsx protein activates either male- or female-
specific genes required for sexual
differentiation.

-Each step in this regulatory cascade -The usefulness of C.elegans is based on

requires a form of processing called RNA the fact that adults consist of approximately
splicing, in which portions of the RNA are 1000 cells, the precise lineage of which can
removed and the remaining fragments are be traced back to specific embryonic
“spliced” back together prior to translation origins.
into a protein.
-There are two sexual phenotypes in
- In the case of the sxl gene, the RNA C.elegans: males, which have only testes,
transcript may be spliced in different ways, and hermaphrodites, which contain both
a phenomenon called alternative splicing. testes andovaries.

-A different RNA transcript is produced in - During larval development of

females than in males. hermaphrodites, testes form that produce
sperm, which is stored. Ovaries are also
-In potential females, the transcript is active produced, but oogenesis does not occur
and initiates a cascade of regulatory gene until the adult stage is reached several days
expression, ultimately leading to female later.
differentiation.
-The eggs that are produced are fertilized
-In potential males, the transcript is inactive, by the stored sperm in a process of self
leading to a different pattern of gene fertilization. The outcome of this process is
activity, whereby male differentiation occurs. quite interesting
Caenorrhabditis elegans -The genetic signal that determines
maleness in contrast to hermaphroditic
development is provided by genes located
on both the X chromosome and autosomes.

-C.elegans lacks a Y chromosome

altogether—hermaphrodites have two X
chromosomes, while males have only one X
chromosome.
-A ratio of 1.0 (two X chromosomes and two
copies of each autosome) results in
hermaphrodites, and a ratio of 0.5 results in
males. The absence of a heteromorphic Y
chromosomeis not uncommon in organisms.