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1. Sex determination

2. Sex Determination Can be
Genetic or Environmental
Two ways in which sex can be determined:
• Environment:
• In some species environmental factors are important
– In turtles sex is determined by temperature of egg development
– In some species environmental factors change the sex at
different stages of life (Social structure)
• Some marine worms change sex (from male to female) when
they get larger
• Coral reef fishes (wrasse) : if the male fish dies the largest
female in the group changes into a new male

3. Environmental Sex Determination…..
• In some cold-blooded vertebrates, some fishes, many
reptiles (e.g. certain snakes, lizards, turtles, and all
crocodiles and alligators) as well as in some
invertebrates (e.g. certain crustaceans), sex is
determined after fertilization — not by sex
chromosomes deposited in the egg.
• The choice is usually determined by the temperature at
which early embryonic development takes place.
• In some cases (e.g. many turtles and lizards), a higher
temperature during incubation favors the production of
females.
• In other cases (e.g., alligators), a higher temperature
favors the production of males.
• Even in cases (e.g. some lizards) where there are sex
chromosomes, a high temperature can convert a
genotypic male (ZZ) into a female.

4. Sex Determination Can be
Genetic or Environmental
• In many species sex is determine solely by the
chromosomes- birds and mammals
• Chromosomes - Three methods:
• XO - Haploid/diploid e.g., bees, haploid males diploid
females
• ZW - Heterogametic (ZW) females, homogametic
(ZZ) males, e.g., birds
• XY - Heterogametic (XY) males, homogametic (XX)
females, e.g.,, humans and Drosophila

5. SEX DETERMINATION
• Sex chromosomes
– X and Y chromosomes
– Homogametic sex
– Heterogametic sex
• Sex determination in Drosophila
– Ratio of X chromosomes to autosomes determines sex
– Numerator and denominator elements
– Gynandromorph
• Sex determination in humans and other mammals
– Y chromosome determines maleness in mammals
– Sex-determining genes
– Hormones and default pathways
– Testicular feminization

6. Reproduction Without Sex and Sex Without
Reproduction Both Occur in Nature
• Sex is the transfer of genes from one cell
to another and in microorganisms this
often occurs without cell division, so that
there is no reproduction
• Many species can reproduce without sex
– Most single-cell organisms
– Some multicellular organisms

7. There Are Many Successful Asexual Species
• Single cells reproduce whenever they divide
• Some multicellular organisms reproduce by
budding or branching from parent (Hydra,
sponges, sea anemones)
• Some higher organisms produce eggs that
develop into new individuals without fertilization ;
called parthenogenesis* (virgin birth)
– Aphids in summer (they become sexual in the fall)
– Whiptail lizards
– Some salamanders
• Offspring of asexual organisms are clones of the
parent (genetically identical)
• *a form of asexual reproduction in which growth
and development of embryos occur without
fertilization

8. More Examples….
– Fission-bi-and multiple,
– Budding-Taenia or Echinococci ,
– Vegetative propagation,
– Fragmentation (some annelid worms, turbellarians and
sea stars), fungi, and plants,
– clonal Fragmentation in multicellular or colonial
organisms is a form of asexual reproduction
echinoderms,
– Agamogenesis*-parthenogenesis, invertebrates (e.g.
water fleas, rotifers, aphids, stick insects, some ants,
bees and parasitic wasps), and vertebrates -e.g. some
reptiles, amphibians, rarely birds.
*reproduction without the fusion of gametes,-asexual
reproduction, as by budding, cell division, or
parthenogenesis.

9. Sexual Reproduction Has Been Adopted by
Most Higher Organisms
• Almost all organisms with eukaryotic cells
undergo sexual reproduction
• The sexual lifestyle:
– Diploid cells: 2 sets of chromosomes
– Meiosis: a type of cell division that produces
reproductive cells that are haploid (1 set of
chromosomes); usually there are 2 types of
reproductive cells, sperms and eggs
– Fertilization: combination of a sperm and egg to
produce a new diploid cell (zygote)
– Development of the zygote into a new individual

10. There Are a Large Number of Natural Sexual
Strategies
• Hermaphrodites have both sexes on same
individual (many flowers, earthworms, snails,
some fish); in earthworms and snails when 2
individuals mate each fertilizes the other
• Alternate sexual and asexual stages (gall wasps,
aphids)
• Fertilization may be internal or external
• Development of embryo may be internal or
external

11. Hermaphrodites
• Hermaphrodites have both male and female sex organs.
Many species of fish are hermaphroditic.
• Some start out as one sex and then, in response to
stimuli in their environment, switch to the other.
• Other species have both testes and ovaries at the same
time (but seldom fertilize themselves). (However,
populations of C. elegans (Caenorhabditis elegans- a
nematode ) consist mostly of hermaphrodites and these
only fertilize themselves)
• Hermaphroditic fishes have no sex chromosomes

12. Advantages of sexual reproduction
• More genetic diversity: more potential for survival of
species when environmental conditions change
– Shuffling of genes in meiosis
– Crossing-over in meiosis
– Fertilization: combines genes from 2 separate individuals
• DNA back-up and repair
– Asexual organisms don't have back-up copies of genes, sexual
organisms have 2 sets of chromosomes and one can act as a
back-up if the other is damaged
– Sexual mechanisms , especially recombination, are used to
repair damaged DNA- the un-damaged chromosome acts as a
template and eventually both chromosomes end up with the
correct gene

13. • Sex Determination in Other Animals
ZZ-ZW System:
• This is essentially the reverse of the XX-XY system, where the
female is ZW and the male ZZ.
• This type of sex determination occurs in some lepidoptera insects
like butterflies and moths. It is also known to occur in several
examples of fishes, reptiles –snakes and birds.
• In birds, moths, schistosomes-A genus of trematodes, commonly
known as blood-flukes, and some lizards, the male has two of the
same chromosome (designated ZZ),
• whereas the female has "heterogametic" chromosomes (designated
Z and W).
• In chickens, a single gene on the Z chromosome (designated
DMRT1- double sex and mab-3 related transcription factor 1
(protein-coding),
• when present in a double dose (ZZ), produces males
• while the presence of only one copy of the gene produces females
(ZW).

14. In this type, the females carry two different types of sex chromosomes (ZW)
and are heterogametic while males carry identical sex chromosomes (ZZ) and
are homogametic.
The ova will be of two types: Z carrying and W carrying while all sperms will be
only Z-carrying.
The ovum will have a sex chromosome composition of ZZ and it develops into
a male.
A zygote with ZW chromosomes, formed by a fusion of Z-carrying sperm with
a W-carrying ovum, results in the formation of a female offspring.

15. Sex chromosome systems
• XX-XO system. This is found in many insect species.
• This is the case in grasshoppers, roaches, and other
insects and the bug Protenor and is sometimes known
as the Protenor system.
• Adult males lack a Y sex chromosome and have only an
X chromosome. They produce sperm cells that contain
either an X chromosome or no sex chromosome, which
is designated as O.
• The females are XX and produce egg cells that contain
an X chromosome.
• If an X sperm cell fertilizes an egg, the resulting zygote
will be XX or female.
• If a sperm cell containing no sex chromosome fertilizes
an egg, the resulting zygote will be XO or male.

16. • Parthenogenesis:
• What about animals like most kinds of wasps, bees,
honeybees and ants that have no sex chromosomes?
• How is sex determined? In these species, fertilization
determines sex.
• If an egg becomes fertilized it will develop into a female.
• A non-fertilized egg may develop into a male.
• The female is diploid and contains two sets of
chromosomes, while the male is haploid.
• This development of an unfertilized egg into an individual
is called parthenogenesis.
• So, sex is determined by the number of autosome sets;
haploid embryos develop into males and diploid embryos
develop into females
• Female, which are derived from fertilized eggs, are
diploid, and males, which are derived from unfertilized
eggs are haploid

17. Sex determination in Drosophila XX-XY.
• This is found in mammals and also in certain insects
including Drosophila (the fruit fly).
• Here females have two copies of the X chromosome and
males have an X and a Y chromosome.
• Although the male fruit fly, Drosophila melanogaster, is
XY, the Y chromosome does not dictate its maleness but
rather the absence of a second X.
• Furthermore, instead of females shutting down one X to
balance the single X of the males — as we do
• — male flies double the output of their single X relative
to that of females.

18. Sex determination in Drosophila
• Sex is also determined in Drosophila by the ratio of X
chromosomes to sets of autosomes (sets of autosomes
simply refers to the ploidy of the fly).
• When the ratio is 1.0 or greater flies are female.
• When it is 0.5 or less flies are male.
• Intermediate values give rise to intersex flies.
• Extreme ratios such as 0.33 and 1.5 give rise to flies that are
called super or metamales and super or metafemales,
respectively.
• These flies are poorly developed and have a shortened life-
span

19. No. of X
chromosomes
(X)
No. of sets of
autosomes (A)
X:A ratios sex
3 2 1.5 Female
3 3 1.0 Female
2 2 1.0 Female
2 3 0.67 Intersex
1 2 0.5 Male
1 3 0.33 Male

20. Table 17.3

21. • Normally, flies have either one or two X chromosomes
and two sets of autosomes. If there is but one X
chromosome in a diploid cell (1X:2A), the fly is male. If
there are two X chromosomes in a diploid cell (2X:2A),
the fly is female. Thus, XO Drosophila are sterile males.
• The fact that sex determination is a result of a balance
of X chromosomes and autosomes suggests that genes
that cause female development are clustered on the X
chromosome and genes for maleness on the autosomes.
• One important point to note concerns the Y
chromosome. The data above indicate that it has no role
in sex determination in Drosophila.
• This is correct, but although flies that lack a Y
chromosome may be male, they are infertile because a
gene on the Y chromosome is essential for the
development of functional sperm.

22. Gynandromorphs: Relatively rare
• One significant feature of sex determination in Drosophila is the
presence of abnormal flies known as gynandromorphs.
• Loss of individual chromosomes can occur in mitotic cell
• These are the result of nondisjunction in the somatic cells of the flies.
• If this results in a change in the number of X chromosomes in a cell the
X : autosome ratio will be changed and may affect the sex of the cell.
• This can occur because in flies sex is determined autonomously in
every cell.
• As the cell continues to divide, its descendants will form a patch of cells
(clone) which, depending on their position in the organism, may
differentiate to form structures of the opposite sex to that of the rest of
the fly.
• A portion of body can have X:A ratio of 0.5 while remainder has an X:A
ratio of 1
• In the most extreme case, loss of an X chromosome in the first division
after fertilization can result in a fly which develops bilaterally into two
halves, one male and the other female.
• This type of event is not found in mammals where the production of
secondary sexual characters is determined hormonally.

23. Sex determining gene in drosophila
• Sxl- gene product act as a master switch for regulatory
cascade that determines whether the male or female
development pathways are activated
• Sxl stands for sex lethal and was named because loss of
function mutations at this locus result in total absence of
homozygous female progeny, with no effect on males
• It is now known that sxl gene product is required for
female development
• And that a regulatory element in its promoter region is
sensitive to the regulatory proteins produced from genes
on X chromosome (numerator element) and on
autosomes (denominator element), respectively

24. • This female-specific activation of Sxl is thought to be
stimulated by “numerator proteins” encoded by the X
chromosome. These numerator proteins include
Sisterless-a and Sisterless-b. These proteins bind to the
“early” promoter of the Sxl gene to promote its
transcription shortly after fertilization.
• The “denominator proteins” are autosomally encoded
proteins such as Deadpan and Extramacrochaetae.
These proteins block the binding or activity of the
numerator proteins.
• The denominator proteins may actually be able to form
inactive heterodimers with the numerator proteins .
• It appears, then, that the X:A ratio is measured by
competition between X-encoded activators and
autosomally encoded repressors of the promoter of the
Sxl gene.

25. In Humans (and Other Mammals) Sex is Determined
Genetically
sex determination by XX-XY type.
• We have 46 chromosomes, 23 pairs
• 22 pairs are called somatic chromosomes
• The 23rd pair consists of two chromosomes, the X and
Y, that are somewhat different from each other
• The X and Y determine sex: a person who is XX is
female; a person who is XY is male
– The X chromosome is required for life, the Y is not
– The sex of a child is always determined by the father- he can
make both X and Y sperm
– The Y chromosome is small and degenerate but it has a gene
controlling the production of testosterone- if this hormone is
present the embryo develops into a male

26. Sex Chromosomes
• This type of sex determination is called XX-XY type.
• In sexual reproduction, the genetic materials from the
two sexes participating are different from each other.
• All human chromosomes are not paired similarly, the sex
chromosomes in men is odd in not always being a
perfect pair.
• It is a mismatched pair in which one is a normal-sized X
while the other is a short one called Y.
• Women have a perfect pair of sex chromosomes,both
called X.

27. • A human sex is predetermined in the sperm gemete.
• The male gametes or sperm cells in humans and
other mammals are heterogametic and contain one of
two types of sex chromosomes. They are either X or
Y.
• The female gametes or eggs however, contain only
the X sex chromosome and are homogametic.
• The sperm cell determines the sex of an individual in
this case. There are two possibilities that can occur
during fertilization.
• Since sperm are the variable factor (which sperm
fertilizes the egg ) they are responsible for sex
determining
• If a sperm cell containing an X chromosome fertilizes
an egg, the resulting zygote will be XX or female.
• If the sperm cell contains a Y chromosome, then the
resulting zygote will be XY or male.
• In human sex determined by a dominant
effect of the SRY gene on the Y chromosome;
the product of this gene, the testis-determining
factor (TDF), causes a human embryo to develop
into a male.

28. Mammalian sex determining genes
• The Y chromosome has been shown to carry a gene
designated SRY in mice and human , whose gene
product is a transcription factor that causes the primitive
gonad to develop into a testis.
• Two testicular hormones are responsible for diverting
development of the rest of the reproductive system from
female pattern to the male
• Mullerian inhibiting factor (MIF) prevents development of
early primordia known as Mullerian ducts into the female
oviducts and uterus
• Testosterone promotes developments of all of the
internal and external male reproductive structures other
than the testes.

29. Sexual differentiation in humans
• All human embryos undergo a hermaphorditic
period, at 5-6 weeks the developing embryos
whether male or female has a pair of
unspecialized gonads and 2 paired duct, the
wolffian and Mullerian, which connect to the
future urethra
• 5th week of gestation, gonadal primordia arise
• Primordial germ cell lines become cortex/inner
medulla
• Cortex-develop into ovary
• Medulla – develop into testis

31. DHT-Dihydrotestosterone- is an androgen, a male sex hormone. Testosterone is
converted to the active androgen DHT by the action of the enzyme 5
alpha reductase

32. Sex Organs Develop from a Unisex Gonad
• At 5-6 weeks the developing embryo, whether male or female has a
pair of unspecialized gonads and 2 paired ducts, the Wolffian and
Mullerian, which connect to the future urethra
• Differentiation into male or female starts at about the 7th week , if
XY chromosome are present , Medulla – develop into testis if no Y
chromosome present, Cortex-develop into ovarian tissue
• If the embryo has a Y chromosome testosterone is produced and
male gonads develop
• If there is no Y chromosome the embryo develops into a female
• Male development:
– Wolffian duct -> vas deferens and epididymis
– Mullerian duct -> degenerates
– Unisex gonads -> testes
– Labioscrotal swellings -> scrotum
– Genital tubercle -> penis
– Testes descend into scrotum in 7th month

33. Female development
If there is no Y chromosome the embryo develops into a
female
Female development
– Mullerian duct -> oviduct and uterus
– Wolffian duct -> degenerates
– Unisex gonads -> ovaries
– Labioscrotal swellings -> labia majora
– Genital tubercle -> clitoris
• Initiation of testis stimulates production of two hormones
that is needed for male sex differentiation
• Males produce spermatocytes at puberty
• Females arrest eggs in meiosis by 25th week

34. Phenotypic Sex May Differ from Genetic and
Gonadal Sex
• Hermaphrodites have both male and female sex
organs
– Double fertilization can produce some XY cells in an
XX individual
– An XY person who is insensitive to testosterone
(receptor defect) will develop some female
characteristics
– Mutation may block production of testosterone in XY
individual
– Some individuals have unusual numbers of X
and Y chromosomes: usually male if there is
at least one Y chromosome

35. Sex determination in humans
• Sex determination in humans is typical of the process in
other mammalian species
• Though the sex chromosomes are XX and XY, the
genetic basis of sex determination differs markedly from
that described for Drosophila.
• Our understanding of this subject comes from the study
of sex chromosome aneuploids
• Aneuploidy of sex chromosomes arises more frequently
than for autosomes
• because very few genes are present on the Y
chromosome,
• and due to the phenomenon of X chromosome
inactivation, only one X chromosome is expressed in any
cell.
• Hence alterations to the numbers of sex chromosomes
have less effect on viability than do changes to the
autosomes.

36. • Not all of sex chromosome configurations result in fertile
individuals and individuals with the more extreme
deviations from normal suffer severe mental retardation.
• From these examples it is clear that at the chromosomal
level the presence of a Y chromosome is the factor
which determines maleness in humans.
• During early embryonic development the presence of a Y
chromosome causes the undifferentiated gonad to grow
more rapidly and subsequently to develop into testes.
• A specific gene, SRY, mapping to the Y chromosome in
both humans and mice has been isolated that is
responsible for the switch from female to male
development in embryos
• In birds, where the ZZ-ZW sex determining system is
essentially the reverse of the XX-XY, the presence of a
W chromosome induces the development of ovaries
from undifferentiated gonads

37. Testicular feminization
• The production of secondary sexual characteristics is also
under genetic control.
• one of most phenotypically spectacular human mutations
causes loss of function of testosterone receptor –which
result in syndrome known as Testicular feminization
• (Tfm) gene in mammals- codes for a protein that acts as
the receptor for the male specific steroid hormone,
testosterone, and is expressed in both males and females.
• Testosterone is produced only in the testes and is
responsible for secondary sexual characteristics in males.
• Mutant alleles of this gene are responsible for a androgen
insensitivity.
• Here, the presence of a Y chromosome causes testes to
form and these produce testosterone.
• However, the hormone has no effect on target cells
because they lack functional testosterone receptors.

38. • Individuals XY males that carry this
mutation on their X chromosomes are
totally unable to respond to testosterone
with this syndrome develop as
phenotypically infertile females.
• They lack oviducts and uterus because
development of these structures is
inhibited by MIF,
• Their gonads are testes but these remain
internal undescended abdominal testes

40. • A different misalignment of primary and
secondary sexual differentiation occurs in
freemartins.
• These are sheep, goats or cattle that
develop as infertile females, but have
defective internal testes.
• Cells of the testes and other organs have
two X chromosomes, but the blood
contains some cells that have X and Y sex
chromosomes.
• This abnormal development is only found
in females that have been a member of a
pair of mixed sex twins.

41. • The embryonic blood supplies of twins in these
species are fused in utero and hence XY blood
cells and hormones can enter the circulation of
the female twin.
• This is sufficient to force the gonads to develop
into testes, and to block partially normal female
development even though the animal is
genetically XX.
• The male twin is not affected by the presence of
XX cells in its blood system.
• These two examples should indicate the
complex interactions that can occur between the
genetic and hormonal determinants of
developmental processes.

42. Evolution of sex chromosomes
• It is generally considered that sex
chromosomes evolved from a pair of
homologous autosomes.
• This process must have taken place a number
of different times during evolution.
• One of the best examples is found in snakes.
Sex chromosomes have been studied in
primitive and highly evolved snake species.
• In primitive species the two sex chromosomes
appear identical (homomorphic).
• The two chromosomes are only differentiated
by the fact that the W chromosome replicates
late in S phase.

43. • In more advanced species W chromosome
becomes reduced in size, heterochromatic
and clearly different from the Z.
• The pair of sex chromosomes retain only a
small region of homology. This is known as
the pseudoautosomal region and is required
to allow the two chromosomes to pair and
segregate accurately at meiosis
• In vertebrates the sex chromosome which is
limited to the heterogametic sex, (Y or W) is
generally found to carry few genes and to
accumulate large amounts of satellite DNA
sequences and constitutive heterochromatin*
• *poorly expressed, e.g., all human chromosomes 1, 9, 16,
and the Y contain large regions of CH. In most organisms,
CH occurs around the chromosome centromere and near
telomeres.

44. • X chromosome is at least partially derived
from the autosomal (non-sex-related)
genome of other mammals, evidenced from
interspecies genomic sequence alignments.
• The X chromosome is notably larger and has
a more active euchromatin region than its Y
chromosome counterpart.
• Further comparison of the X and Y reveal
regions of homology between the two.
• However, the corresponding region in the Y
appears far shorter and lacks regions that are
conserved in the X throughout primate
species, implying a genetic degeneration for
Y in that region.

45. • As males have only one X chromosome,
they are more likely to have an X
chromosome-related disease.
• It is estimated that about 10% of the genes
encoded by the X chromosome are
associated with a family of "CT" genes,
• so named because they encode for
markers found in both tumor cells (in
cancer patients) as well as in the human
testis (in healthy patients).

48. ZZ-ZO System:
•In this type, the females have only one sex chromosome
and hence represented as ZO.
• Females are heterogametic.
• Males carry two identical sex chromosomes designated
ZZ.
•Males are homogametic.
•On fertilization by a Z-carrying sperm the Z-carrying ovum
would develop into a male (ZZ) and on fertilization, the Z-
lacking ovum would develop into a female.

49. • This type of sex determination occurs in insects and mammals including
human beings. Here, the females have two identical homologous sex
chromosomes designated as XX and the males have two dissimilar sex
chromosomes designated as X and Y. Thus, females are homogametic,
producing only one type of ovum, and males are heterogametic, producing
two types of gametes: half carrying the X chromosome and the other half
carrying the Y chromosome. In Drosophila the Y chromosome has a small
hook like projection. In some plants such as Melandrium alba the Y
chromosome is distinctly longer than the X chromosome. In humans, the Y
chromosome is shorter in length than the X chrmosome. Hence, in all
examples of XX-XY type of allosomes, the females are homogametic and
the males are heterogametic. The male gametes will be of two types and
this condition is called digamety. The X-carrying sperms are called
gynosperms and the Y carrying sperms are called androsperms.
• In all such cases, sex gets determined at the time of fertilization and
depends on the type of sperm that fuses with the ovum. If the X-carrying
ovum is fertilised by a X-carrying sperm the resulting zygote will have a sex
chromosome composition of XX. Such a zygote develops into a female. If
the X carrying ovum is fertilised by a Y-carrying sperm. The resulting zygote
will have a sex chromosome composition of XY. Such a zygote develops
into a male.

50. Sex determinationis controlledby global regulatorygenes, such as tra-1 in
Caenorhabditis elegans, Sex lethal in Drosophila, or Sry in mammals. How
these genes coordinatesexual differentiationthroughoutthe body is a key
unansweredquestion. tra-1 encodes a zinc finger transcriptionfactor,
TRA-1A, that regulates, directlyor indirectly, all genes required for sexual
development. mab-3 (male abnormal 3), acts downstream of tra-1 and is
known to be required for sexual differentiationof at least two tissues. mab-
3 directly regulates yolk protein transcriptionin the intestineand specifies
male sense organ differentiationin the nervous system. It encodes a
transcriptionfactor relatedto the products of the Drosophilasexual
regulator doublesex (dsx), which also regulates yolk proteintranscription
and male sense-organdifferentiation. The similaritiesbetween mab-3 and
dsx led us to suggest that some aspects of sex determinationmay be
evolutionarilyconserved.Here we find that mab-3 is also required for
expressionof male-specificgenes in sensory neurons of the head and tail
and for male interactionwith hermaphrodites. These roles in male
developmentand behaviorsuggest further functionalsimilarityto dsx. In
male sensory ray differentiationwe find that MAB-3 acts synergistically
with LIN-32, a neurogenic bHLH transcriptionfactor. Expressionof LIN-
32 is spatiallyrestrictedby the combined actionof the Hox gene mab-5 and
the hairyhomolog lin-22,while MAB-3 is expressed throughoutthe lateral
hypodermis. Finally, we find that mab-3 transcriptionis directly regulated
in the intestineby TRA-1A, providinga molecularlink between the global
regulatorypathway and terminal sexual differentiation.

51. : Immediately after fertilization there is an assessment of
the ratio of X chromosomes to autosomes. Three genes
are X linked: when there are two X chromosomes, as in
females, the ratio of their gene products like Runt
(Torres, 1994), Sisterless-A and Sisterless-B (also
known as Scute) is higher than in males. These three
genes bind the Sex-lethal promoter and induce
activation. In the case of males, where there is only one
X chromosome, the autosomal proteins Daughterless,
Deadpan and Extramachrochaete, absent sufficient
activator proteins, act as repressors of Sex lethal.

52. • . In the spotlight here is dosage compensation, regulated by Sex lethal. The immediate target of SXL is male
specific lethal-2 (MSL-2), a transcription factor. In the presence of SXL, MSL-2 is spliced into an inactive form, one
that cannot function in dosage compensation. In the absence of SXL (in males), MSL-2 splicing is productive, and
the active MSL-2 transcription factor effectively carries out dosage compensation.
• A word about dosage compensation is in order. The ratio of sex chromosomes to autosomes in females (1:1) is
different from the ratio in males (0.5:1). This is because males, by definition, have one X chromosome and not
two. This presents a dosage problem. The ratio of gene products coded for by the sex chromosome will be
different in males and females, unless some compensatory action is taken. The sex chromosome carries a lot of
genes that are simply along for the ride, and the creation of a dosage imbalance spells catastrophe for
development. What to do?
• Two alternatives are possible. One of the X chromosomes could be shut off, inactivated in females. This is the
solution humans and other higher vertebrates have employed. A second option would be to heighten the activity of
the single X chromosome in males. This is the route flies take. MSL-2, spliced into a functional form in males,
serves to heighten transcriptional activation of the solitary X chromosome. MSL-2 acts in concert with three
partners in this task: Maleless, Male-specific lethal-1 and Male specific lethal-3. They bind to about one hundred
sites on the male chromosome, modifying the chromatin structure to permit heightened gene activation (Bashaw,
1995). The action of these male specific transcription factors is very similar to proteins of the trithorax complex.
• Act 3. In the center ring here is the regulation by Sex lethal of sex specific RNA splicing in ovaries. Ovaries
represent a completely different tissue milieu from somatic cells, and consequently Sex-lethal splicing in these
tissues will demand a different kind of regulation (Granadino, 1993). Germ line Sex-lethal function requires an XX
karyotype, a female soma, and action of the genes ovp, otu and snf (sans fille). SNF is an RNA binding protein
and an integral component of the machinery required for splice site recognition (Flickinger, 1994 and Salz, 1996).
ovo, a zinc finger protein and presumably a transcription factor, has a higher level of transcription in females than
in males, responding to the number of sex chromosomes in the cell (Oliver, 1994). otu (ovarian tumor) gene also
acts upstream of Sex lethal (Pauli, 1993 and Bopp, 1993). Thus ovarian Sex lethal activation and splicing is
regulated by a completely different set of proteins (with the exception of SNF, whose function is general) from
those in the embryo.
• Biological systems operate at a level of complexity that continually astounds the student. A tiny fly carries a whole
circus at the core of its development, as far as sex determination is concerned.