Editing XY sex-determination system (section)

===Genetic===
[[File:PBB Protein SRY image.jpg|right|thumb|PBB Protein SRY image]]
In an interview for the ''Rediscovering Biology'' website,<ref>{{cite web | vauthors = 	Vilain E | date = | title = Rediscovering Biology, Unit 11 - Biology of Sex and Gender, Expert interview transcripts | url = http://www.learner.org/courses/biology/units/gender/experts/vilain.html | archive-url = https://web.archive.org/web/20100823063603/http://www.learner.org/courses/biology/units/gender/experts/vilain.html | archive-date=2010-08-23 | publisher = Annenberg Media }}</ref> researcher [[Eric Vilain]] described how the paradigm changed since the discovery of the SRY gene:
{{Blockquote|text=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 an interview by ''[[Scientific American]]'' in 2007, Vilian 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?"<ref>{{Cite web| vauthors = Lehrman S |title=When a Person Is Neither XX nor XY: A Q&A with Geneticist Eric Vilain|url=https://www.scientificamerican.com/article/q-a-mixed-sex-biology/|access-date=2021-08-08|website=Scientific American|language=en}}</ref> He replied:

{{Blockquote|text=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 syndrome|Klinefelter]] [a male who is XXY] and [[Turner syndrome|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 finding testis-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.}}

In mammals, including humans, the SRY gene triggers 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,<ref>
{{cite journal | vauthors = Uhlenhaut NH, Jakob S, Anlag K, Eisenberger T, Sekido R, Kress J, Treier AC, Klugmann C, Klasen C, Holter NI, Riethmacher D, Schütz G, Cooney AJ, Lovell-Badge R, Treier M | title = Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation | journal = Cell | volume = 139 | issue = 6 | pages = 1130–1142 | date = December 2009 | pmid = 20005806 | doi = 10.1016/j.cell.2009.11.021 | doi-access = free }}</ref> regulated by the expression of a "pro-female" gene, [[FOXL2]]. In an interview<ref>{{cite web | url = http://www.timesonline.co.uk/tol/news/science/genetics/article6952050.ece | title = Scientists find single 'on-off' gene that can change gender traits | archive-url = https://web.archive.org/web/20110814125506/http://www.timesonline.co.uk/tol/news/science/genetics/article6952050.ece | archive-date=2011-08-14 | vauthors = Devlin H | work = The Times | date = December 11, 2009 }}</ref> for the ''TimesOnline'' edition, study co-author Robin Lovell-Badge explained the significance of the discovery:
{{Blockquote|text=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 [[Drosophila melanogaster|fruit flies]] and animal models to attempt an understanding of how the genetics of sexual differentiation can influence biological processes like reproduction, ageing<ref>
{{cite journal | vauthors = Tower J, Arbeitman M | title = The genetics of gender and life span | journal = Journal of Biology | volume = 8 | issue = 4 | pages = 38 | year = 2009 | pmid = 19439039 | pmc = 2688912 | doi = 10.1186/jbiol141 | doi-access = free }}</ref> and disease.