XY sex-determination system
The XY sex-determination system is a sex-determination system used to classify many mammals, including humans, some insects (Drosophila), some snakes, some fish (guppies), and some plants (Ginkgo tree). In this system, the sex of an individual is determined by a pair of sex chromosomes. Females have two of the same kind of sex chromosome (XX), and are called the homogametic sex. Males have two different kinds of sex chromosomes (XY), and are called the heterogametic sex.
In humans, the presence of the Y chromosome is responsible for triggering male development; in the absence of the Y chromosome, the fetus will undergo female development. More specifically, it is the SRY gene located on the Y chromosome that is of importance to male differentiation. In very rare circumstances, a gene translocation will result in the SRY-gene transferring to an X chromosome. In most species with XY sex determination, an organism must have at least one X chromosome in order to survive.
The XY system contrasts in several ways with the ZW sex-determination system found in birds, some insects, many reptiles, and various other animals, in which the heterogametic sex is female. It had been thought for several decades that in all snakes' sex was determined by the ZW system, but there had been observations of unexpected effects in the genetics of species in the families Boidae and Pythonidae; for example, parthenogenic reproduction produced only females rather than males, which is the opposite of what is to be expected in the ZW system. In the early years of the 21st century such observations prompted research that demonstrated that all pythons and boas so far investigated definitely have the XY system of sex determination.
A temperature-dependent sex determination system is found in some reptiles and fish.
All animals have a set of DNA coding for genes present on chromosomes. In humans, most mammals, and some other species, 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.
In mammals female is the default sex. Even before the discovery of SRY, the notion of female as the mammalian default sex was established experimentally. It should be kept in mind that mammal sex determination is complex.
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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. 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.
Other species (including most Drosophila species) use the presence of two X chromosomes to determine femaleness: one X chromosome gives putative maleness, but the presence of Y chromosome genes is required for normal male development. In the fruit fly individuals with XY are male and individuals with XX are female; however, individuals with XXY or XXX can also be female, and individuals with X can be males.
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Many insects of the order Hymenoptera instead have a haplo-diploid system, where the males are haploid (having 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.
In an interview for the Rediscovering Biology website, 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 a 2007 interview on Scientific American Eric Vilian when he was asked “It sounds as if you are describing a shift from the prevailing view that female development is a default molecular pathway to active pro-male and antimale pathways. Are there also pro-female and antifemale pathways?” He responded with
Modern sex determination started at the end of the 1940s—1947—when the French physiologist Alfred Jost said it's the testis that is determining sex. Having a testis determines maleness, not having a testis determines femaleness. The ovary is not sex-determining. It will not influence the development of the external genitalia. Now in 1959 when the karyotype of Klinefelter [a male who is XXY] and Turner [a female who has one X] syndromes was discovered, it became clear that in humans it was the presence or the absence of the Y chromosome that's sex determining. Because all Klinefelters that have a Y are male, whereas Turners, who have no Y, are females. So it's not a dosage or the number of X's, it's really the presence or absence of the Y. So if you combine those two paradigms, you end up having a molecular basis that's likely to be a factor, a gene, that's a testis-determining factor, and that's the sex-determining gene. So the field based on that is really oriented towards findingtestis-determining factors. What we discovered, though, was not just pro-testis determining factors. There are a number of factors that are there, like WNT4, like DAX1, whose function is to counterbalance the male pathway.— Eric Vilian
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 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 suggests that ovary development and maintenance is an active process, regulated by the expression of a "pro-female" gene, FOXL2. In an interview 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.
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 and disease.
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.
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.
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.
The time at which insemination occurs during the estrus cycle has been found to affect the sex ratio of the offspring of humans, cattle, hamsters, and other mammals. Hormonal and pH conditions within the female reproductive tract vary with time, and this affects the sex ratio of the sperm that reach the egg.
Sex-specific mortality of embryos also occurs.
Ancient ideas on sex determination
Aristotle believed incorrectly that the sex of an infant is determined by how much heat a man's sperm had during insemination. He wrote:
...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 in error that the male principle was the driver behind sex determination, such that if the male principle was insufficiently expressed during reproduction, the fetus would develop as a female.
20th century genetics
Nettie Stevens and Edmund Beecher Wilson are credited with independently discovering, in 1905, the chromosomal XY sex-determination system, i.e. the fact that males have XY sex chromosomes and females have XX sex chromosomes.
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, who castrated embryonic rabbits in utero and noticed that they all developed as female.
In 1959, C. E. Ford and his team, in the wake of Jost's experiments, discovered 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 Klinefelter syndrome (XXY), which implicated the presence of a Y chromosome in development of maleness.
All these observations lead to a consensus that a dominant gene that determines testis development (TDF) must exist on the human Y chromosome. The search for this testis-determining factor (TDF) led a team of scientists in 1990 to discover a region of the Y chromosome that is necessary for the male sex determination, which was named SRY (sex-determining region of the Y chromosome).
- Sexual differentiation (human)
- Secondary sex characteristic (human)
- Y-chromosomal Adam
- Sex Determination in Silene
- Sex-determination system
- Sexual differentiation
- Haplodiploid sex-determination system
- Z0 sex-determination system
- X0 sex-determination system
- ZW sex-determination system
- Temperature-dependent sex determination
- X chromosome
- Y chromosome
- Hake, Laura; O'Connor, Clare. "Genetic Mechanisms of Sex Determination | Learn Science at Scitable". www.nature.com. Retrieved 2021-04-13.
- "Can a Zygote Survive Without an X Sex Chromosome?". Education - Seattle PI. Retrieved 2020-11-08.
- Sherwood, Susan. "What Occurs When the Zygote Has One Fewer Chromosome than Usual?". Sciencing. Retrieved 2021-04-29.
- Gamble, Tony; Castoe, Todd A.; Nielsen, Stuart V.; Banks, Jaison L.; Card, Daren C.; Schield, Drew R.; Schuett, Gordon W.; Booth, Warren (2017). "The Discovery of XY Sex Chromosomes in a Boa and Python". Current Biology. 27 (14): 2148–2153.e4. doi:10.1016/j.cub.2017.06.010. PMID 28690112.
- Olena, Abby. Snake Sex Determination Dogma Overturned. The Scientist July 6, 2017 
- Cronk, Quentin; Müller, Niels A. (2020-07-29). "Default Sex and Single Gene Sex Determination in Dioecious Plants". Frontiers in Plant Science. 11: 1162. doi:10.3389/fpls.2020.01162. ISSN 1664-462X. PMC 7403218. PMID 32849717.
- 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. Bibcode:1970RSPTB.259..119J. doi:10.1098/rstb.1970.0052. JSTOR 2417046. PMID 4399057.
- Wallis MC, Waters PD, Graves JA (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. S2CID 31675679.
- Cortez, Diego; Marin, Ray; Toledo-Flores, Deborah; Froidevaux, Laure; Liechti, Angélica; Waters, Paul D.; Grützner, Frank; Kaessmann, Henrik (24 April 2014). "Origins and functional evolution of Y chromosomes across mammals". Nature. 508 (7497): 488–493. Bibcode:2014Natur.508..488C. doi:10.1038/nature13151. PMID 24759410. S2CID 4462870.
- 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.
- Badenhorst, Daleen; Stanyon, Roscoe; Engstrom, Tag; Valenzuela, Nicole (2013-04-01). "A ZZ/ZW microchromosome system in the spiny softshell turtle, Apalone spinifera, reveals an intriguing sex chromosome conservation in Trionychidae". Chromosome Research. 21 (2): 137–147. doi:10.1007/s10577-013-9343-2. ISSN 1573-6849. PMID 23512312. S2CID 14434440.
- Fusco G, Minelli A (2019-10-10). The Biology of Reproduction. Cambridge University Press. pp. 306–308. ISBN 978-1-108-49985-9.
- Mittwoch, Ursula (2014-06-28). Sex Chromosomes. Academic Press. p. 12. ISBN 978-1-4832-5858-4.
- Gradstein, Stephan Robbert; Klatt, Simone; Normann, Felix; Wilson, Rosemary; Weigelt, Patrick; Willmann, Rainer (2008). Systematics 2008 Göttingen, Programme and Abstracts. Universitätsverlag Göttingen. p. 278. ISBN 978-3-940344-23-6.
- Monéger, Françoise (2007). "Sex Determination in Plants". Plant Signaling & Behavior. 2 (3): 178–179. ISSN 1559-2316. PMC 2634050. PMID 19704689.
- Hakeem, Khalid Rehman; Tombuloğlu, Hüseyin; Tombuloğlu, Güzin (2016-08-23). Plant Omics: Trends and Applications. Springer. p. 365. ISBN 978-3-319-31703-8.
- Smith, Craig A.; Sinclair, Andrew H. (February 2004). "Sex determination: insights from the chicken". BioEssays. 26 (2): 120–132. doi:10.1002/bies.10400. ISSN 0265-9247. PMID 14745830.
- "5 Types of Sex Determination in Animals". genetics.knoji.com. Archived from the original on 5 February 2017. Retrieved 3 May 2018.
- Rediscovering Biology, Unit 11 - Biology of Sex and Gender, Expert interview transcripts, Link Archived 2010-08-23 at the Wayback Machine
- Lehrman, Sally. "When a Person Is Neither XX nor XY: A Q&A with Geneticist Eric Vilain". Scientific American. Retrieved 2021-08-08.
- 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 Archived 2011-08-14 at the Wayback Machine, 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. PMID 7605846. S2CID 27957961.
- 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 Archived October 2, 2015, at the Wayback Machine
- De Generatione Animalium, 766B 15‑17.
- Brush, Stephen G. (June 1978). "Nettie M. Stevens and the Discovery of Sex Determination by Chromosomes". Isis. 69 (2): 162–172. doi:10.1086/352001. JSTOR 230427. PMID 389882. S2CID 1919033.
- "Nettie Maria Stevens – DNA from the Beginning". www.dnaftb.org. Archived from the original on 2012-10-01. Retrieved 2016-07-07.
- John L. Heilbron (ed.), The Oxford Companion to the History of Modern Science, Oxford University Press, 2003, "genetics".
- Jost A., Recherches sur la differenciation sexuelle de l’embryon de lapin, Archives d'anatomie microscopique et de morphologie experimentale, 36: 271 – 315, 1947.
- 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. Bibcode:1959Natur.183..302J. doi:10.1038/183302a0. PMID 13632697. S2CID 38349997.
- Schoenwolf, Gary C. (2009). "Development of the Urogenital system". Larsen's human embryology (4th ed.). Philadelphia: Churchill Livingstone/Elsevier. pp. 307–9. ISBN 9780443068119.
- 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. Bibcode:1990Natur.346..240S. doi:10.1038/346240a0. PMID 1695712. S2CID 4364032.
- Sex Determination and Differentiation
- SRY: Sex determination from the National Center for Biotechnology Information
- Can Mammalian Mothers Control the Sex of their Offspring? (KQED Science article on San Diego Zoo research.)
- Maternal Diet and Other Factors Affecting Offspring Sex Ratio: A Review, published in Biology of Reproduction
- Sex Determination and the Maternal Dominance Hypothesis
- Sperm-Ovum Interactions at WikiGenes