XY sex-determination system

Drosophila sex-chromosomes

Ginkgo biloba

The XY sex-determination system is the sex-determination system found in humans, most other
mammals, some insects (Drosophila), and some plants (Ginkgo). In this system, the sex of an
individual is determined by a pair of sex chromosomes (gonosomes). Females have two of the
same kind of sex chromosome (XX), and are called the homogametic sex. Males have two
distinct sex chromosomes (XY), and are called the heterogametic sex.

This system is in contrast with the ZW sex-determination system found in birds, some insects,
many reptiles, and other animals, in which the heterogametic sex is female.

A temperature-dependent sex determination system is found in some reptiles.

Mechanisms
All animals have a set of DNA coding for genes present on chromosomes. In humans, most
mammals, and some other species[who?], two of the chromosomes, called the X chromosome and
Y chromosome, code for sex. In these species, one or more genes are present on their Y-
chromosome that determine maleness. In this process, an X chromosome and a Y chromosome
act to determine the sex of offspring, often due to genes located on the Y chromosome that code
for maleness. Offspring have two sex chromosomes: an offspring with two X chromosomes will
develop female characteristics, and an offspring with an X and a Y chromosome will develop
male characteristics.

Humans
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Human male XY chromosomes after G-banding

In humans, a single gene (SRY) present on the Y chromosome acts as a signal to set the
developmental pathway towards maleness. Presence of this gene starts off the process of
virilization. This and other factors result in the sex differences in humans.[1] The cells in females,
with two X chromosomes, undergo X-inactivation, in which one of the two X chromosomes is
inactivated. The inactivated X chromosome remains within a cell as a Barr body.

Humans, as well as some other organisms, can have a chromosomal arrangement that is contrary
to their phenotypic sex; for example, XX males or XY females (see androgen insensitivity
syndrome). Additionally, an abnormal number of sex chromosomes (aneuploidy) may be present,
such as Turner's syndrome, in which a single X chromosome is present, and Klinefelter's
syndrome, in which two X chromosomes and a Y chromosome are present, XYY syndrome and
XXYY syndrome.[1] Other less common chromosomal arrangements include: triple X syndrome,
48, XXXX, and 49, XXXXX.

Other animals

XY system in mammals: Sex is determined by presence of Y. "Female" is the default sex; due to
the absence of the Y.[2] In the 1930s, Alfred Jost determined that the presence of testosterone was
required for Wolffian duct development in the male rabbit.[3]

SRY is an intronless sex-determining gene on the Y chromosome in the therians (placental

Other systems

Main article: Sex determination system

Birds and many insects have a similar system of sex determination (ZW sex-determination
system), in which it is the females that are heterogametic (ZW), while males are homogametic
(ZZ).

Many insects of the order Hymenoptera instead have a system (the haplo-diploid sex-
determination system), where the males are haploid individuals (which just one chromosome of
each type), while the females are diploid (with chromosomes appearing in pairs). Some other
insects have the X0 sex-determination system, where just one chromosome type appears in pairs
for the female but alone in the males, while all other chromosomes appear in pairs in both sexes.

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Influences
Genetic

PBB Protein SRY image

For a long time, biologists believed that the female form was the default template for the
mammalian fetuses of both sexes. After the discovery of the testis-determining gene SRY, many
scientists shifted to the theory that the genetic mechanism that determines a fetus to develop into
a male form was initiated by the SRY gene, which was thought to be responsible for the
production of testosterone and its overall effects on body and brain development. This
perspective still shared the classical way of thinking; that in order to produce two sexes, nature
has developed a default female pathway and an active pathway by which male genes would
initiate the process of determining a male sex, as something that is developed in addition to and
based on the default female form. This view is no longer considered accurate by most scientists
who study the genetics of sex. In an interview for the Rediscovering Biology website,[5]
researcher Eric Vilain described how the paradigm changed since the discovery of the SRY gene:

For a long time we thought that SRY would activate a cascade of male genes. It turns out that the
sex determination pathway is probably more complicated and SRY may in fact inhibit some anti-
male genes.

The idea is instead of having a simplistic mechanism by which you have pro-male genes going
all the way to make a male, in fact there is a solid balance between pro-male genes and anti-male
genes and if there is a little too much of anti-male genes, there may be a female born and if there
is a little too much of pro-male genes then there will be a male born.

We [are] entering this new era in molecular biology of sex determination where it's a more subtle
dosage of genes, some pro-males, some pro-females, some anti-males, some anti-females that all
interplay with each other rather than a simple linear pathway of genes going one after the other,
which makes it very fascinating but very complicated to study.

In mammals, including humans, the SRY gene is responsible with triggering the development of
non-differentiated gonads into testes, rather than ovaries. However, there are cases in which

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testes can develop in the absence of an SRY gene (see sex reversal). In these cases, the SOX9
gene, involved in the development of testes, can induce their development without the aid of
SRY. In the absence of SRY and SOX9, no testes can develop and the path is clear for the
development of ovaries. Even so, the absence of the SRY gene or the silencing of the SOX9 gene
are not enough to trigger sexual differentiation of a fetus in the female direction. A recent finding
indicates that ovary development and maintenance is an active process,[6] regulated by the
expression of a "pro-female" gene, FOXL2. In an interview[7] for the TimesOnline edition, study
co-author Robin Lovell-Badge explained the significance of the discovery:

We take it for granted that we maintain the sex we are born with, including whether we have
testes or ovaries. But this work shows that the activity of a single gene, FOXL2, is all that
prevents adult ovary cells turning into cells found in testes.

Implications

Looking into the genetic determinants of human sex can have wide-ranging consequences.
Scientists have been studying different sex determination systems in fruit flies and animal
models to attempt an understanding of how the genetics of sexual differentiation can influence
biological processes like reproduction, ageing[8] and disease.

Maternal

In humans and many other species of animals, the father determines the sex of the child. In the
XY sex-determination system, the female-provided ovum contributes an X chromosome and the
male-provided sperm contributes either an X chromosome or a Y chromosome, resulting in
female (XX) or male (XY) offspring, respectively.

Hormone levels in the male parent affect the sex ratio of sperm in humans.[9] Maternal influences
also impact which sperm are more likely to achieve conception.

Human ova, like those of other mammals, are covered with a thick translucent layer called the
zona pellucida, which the sperm must penetrate to fertilize the egg. Once viewed simply as an
impediment to fertilization, recent research indicates the zona pellucida may instead function as a
sophisticated biological security system that chemically controls the entry of the sperm into the
egg and protects the fertilized egg from additional sperm.[10]

Recent research indicates that human ova may produce a chemical which appears to attract
sperm and influence their swimming motion. However, not all sperm are positively impacted;
some appear to remain uninfluenced and some actually move away from the egg.[11]

Maternal influences may also be possible that affect sex determination in such a way as to
produce fraternal twins equally weighted between one male and one female.[12]

The time at which insemination occurs during the oestrus cycle has been found to affect the sex
ratio of the offspring of humans, cattle, hamsters, and other mammals.[9] Hormonal and pH

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conditions within the female reproductive tract vary with time, and this affects the sex ratio of
the sperm that reach the egg.[9]

Sex-specific mortality of embryos also occurs.[9]

History
Ancient ideas on sex determination

Since ancient times, people have believed that the sex of an infant is determined by how much
heat a man's sperm had during insemination. Aristotle wrote that:

...the semen of the male differs from the corresponding secretion of the female in that it contains
a principle within itself of such a kind as to set up movements also in the embryo and to concoct
thoroughly the ultimate nourishment, whereas the secretion of the female contains material
alone. If, then, the male element prevails it draws the female element into itself, but if it is
prevailed over it changes into the opposite or is destroyed.

Aristotle claimed that the male principle was the driver behind sex determination,[13] such that if
the male principle was insufficiently expressed during reproduction, the fetus would develop as a
female. In contrast, modern genetics has developed a view on sex determination in which no one
single factor is responsible for determining sex; a number of pro-male, anti-male and pro-female
genes being responsible, though the largest factor is whether the male's gamete carries an X or Y
chromosome.

Beginnings of genetics of sex determination

Edmund Beecher Wilson and Nettie Stevens are credited with discovering, in 1905, the
chromosomal XY sex-determination system; the fact that males have XY sex chromosomes and
females have XX sex chromosomes.[citation needed]

The first clues to the existence of a factor that determines the development of testis in mammals
came from experiments carried out by Alfred Jost,[14] who castrated embryonic rabbits in utero
and noticed that they all developed as female.[citation needed]

In 1959, C. E. Ford and his team, in the wake of Jost's experiments, discovered [15] that the Y
chromosome was needed for a fetus to develop as male when they examined patients with
Turner's syndrome, who grew up as phenotypic females, and found them to be X0 (hemizygous
for X and no Y). At the same time, Jacob & Strong described a case of a patient with
Klienfelter's syndrome (XXY),[16] which implicated the presence of a Y chromosome in
development of maleness.[17]

All these observations lead to a consensus that a dominant gene that determines testis
development (TDF) must exist on the human Y chromosome.[17] The search for this testis-
determining factor (TDF) led a team of scientists[18] in 1990 to discover a region of the Y
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chromosome that is necessary for the male sex determination, which was named SRY (Sex-
determining Region of the Y chromosome).[17]

See also
• Intersexuality for information on variations in human sexual forms
• Sexual differentiation, (human)
• Y-chromosomal Adam

References
1.

• Fauci, Anthony S.; Braunwald, Eugene; Kasper, Dennis L.; Hauser, Stephen L.; Longo, Dan
L.; Jameson, J. Larry; Loscalzo, Joseph (2008). Harrison's Principles of Internal Medicine (17th
ed.). McGraw-Hill Medical. pp. 2339–2346. ISBN 978-0-07-147693-5.
• • "Sex determination and differentiation" (PDF). Utrecht University - Department of Biology.
Ultrecht, Netherlands. Retrieved 13 November 2014.
• • Jost, A.; Price, D.; Edwards, R. G. (1970). "Hormonal Factors in the Sex Differentiation of
the Mammalian Foetus [and Discussion]". Philosophical Transactions of the Royal Society B:
Biological Sciences 259 (828): 119–31. doi:10.1098/rstb.1970.0052. JSTOR 2417046.
• • Wallis MC, Waters PD, Graves JA; Waters; Graves (June 2008). "Sex determination in
mammals - Before and after the evolution of SRY". Cell. Mol. Life Sci. 65 (20): 3182–95.
doi:10.1007/s00018-008-8109-z. PMID 18581056.
• • Rediscovering Biology, Unit 11 - Biology of Sex and Gender, Expert interview transcripts,
Link
• • Uhlenhaut, N. Henriette; et al. (2009). "Somatic Sex Reprogramming of Adult Ovaries to
Testes by FOXL2 Ablation". Cell 139 (6): 1130–42. doi:10.1016/j.cell.2009.11.021.
PMID 20005806.
• • Scientists find single ‘on-off’ gene that can change gender traits, Hannah Devlin, The
Times, December 11, 2009.
• • Tower, John; Arbeitman, Michelle (2009). "The genetics of gender and life span". Journal
of Biology 8 (4): 38. doi:10.1186/jbiol141. PMC 2688912. PMID 19439039.
• • Krackow, S. (1995). "Potential mechanisms for sex ratio adjustment in mammals and
birds". Biological Reviews 70 (2): 225–241. doi:10.1111/j.1469-185X.1995.tb01066.x.
• • Suzanne Wymelenberg, Science and Babies, National Academy Press, 1990, page 17
• • Richard E. Jones and Kristin H. Lopez, Human Reproductive Biology, Third Edition,
Elsevier, 2006, page 238
• • Familial recurrence of gender-balanced twins
• • De Generatione Animalium, 766B 15-17.
• • Jost A., Recherches sur la differenciation sexuelle de l’embryon de lapin, Archives
d'anatomie microscopique et de morphologie experimentale, 36: 271 – 315, 1947.

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• • FORD, CE; JONES, KW; POLANI, PE; DE ALMEIDA, JC; BRIGGS, JH (Apr 4, 1959). "A
sex-chromosome anomaly in a case of gonadal dysgenesis (Turner's syndrome)". Lancet 1
(7075): 711–3. doi:10.1016/S0140-6736(59)91893-8. PMID 13642858.
• • JACOBS, PA; STRONG, JA (Jan 31, 1959). "A case of human intersexuality having a
possible XXY sex-determining mechanism.". Nature 183 (4657): 302–3. doi:10.1038/183302a0.
PMID 13632697.
• • Schoenwolf, Gary C. (2009). "Development of the Urogenital system". Larsen's human
embryology (4th ed.). Philadelphia: Churchill Livingstone/Elsevier. pp. 307–9.
ISBN 9780443068119.

18. • Sinclair, Andrew H.; et al. (19 July 1990). "A gene from the human sex-determining
region encodes a protein with homology to a conserved DNA-binding motif". Nature 346
(6281): 240–244. doi:10.1038/346240a0. PMID 1695712.