|Embryology - 28 Apr 2016 Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 History
- 4 Y Chromosome Genes
- 5 Male Sex Determination
- 6 Testis-specific Protein Y Chromosome
- 7 Pseudoautosomal Regions
- 8 References
- 9 External Links
- 10 Glossary Links
Humans have 23 pairs of chromosomes, 22 autosomes and a pair of sex chromosomes. Males have one X and one Y chromosomes (46, XY) and females have a pair of X chromosomes (46, XX). The Y chromosome is much smaller than the X chromosome and contains 50 million base pairs encoding approximately 200+ genes. The Sry gene (location Yp11.3), found in 1990, encodes is responsible for male sex determination. SRY mutations lead to XY sex reversal in humans, and XX mice with an SRY transgene develop as fertile males. Interestingly, the laboratory rat, Rattus norvegicus, has at least 6 full length copies of the Sry gene.
SRY encodes a 204 amino acid protein that is a member of the HMG (High mobility group) box class of DNA-binding proteins. Transcription factors bind to specific sites of DNA and regulates the transcription (expression) of other genes.
The male-specific region of the human Y chromosome was originally called the non-recombining portion of the Y chromosome (NRY). This region consists of three different classes of euchromatic sequences:
- ampliconic sequences
The Y and X chromosome are both transcriptionally silenced during spermatogenesis, at primary spermatocyte stage onward, by a process called meiotic sex chromosome inactivation (MSCI). (More? Meiosis)
Idiogram Chromosome Banding - The term refers to the light and dark pattern, seen after staining with a dye, of individual chromosomes identified in metaphase. It is only in meiosis and mitosis during metaphase that chromosomes can be easily identified, during the normal cell life (interphase) the chromosomes are unravelled and distributed within the nucleus in chromosome territories. A band is that part of a chromosome which is clearly distinguishable from nearby regions by appearing darker or brighter with one or more banding techniques.
- Human Idiogram: 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | X | Y
- Inheritance Pattern images: Autosomal dominant inheritance | Autosomal recessive inheritance | X-Linked dominant (affected father) | X-Linked dominant (affected mother) | X-Linked recessive (affected father) | X-Linked recessive (carrier mother) | Mitochondrial genome inheritance | Codominant inheritance | Genogram symbols | Genetics
- Genital Links: Introduction | Lecture - Medicine | Lecture - Science | Medicine - Practical | Primordial Germ Cell | Meiosis | Female | Ovary | Oocyte | Uterus | Vagina | Reproductive Cycles | Menstrual Cycle | Male | Testis | Spermatozoa | Prostate | Genital Movies | Abnormalities | Assisted Reproductive Technology | Puberty | Category:Genital
|Historic Embryology - Genital|
|1902 The Uro-Genital System | 1912 Urinogenital Organ Development | 1921 Urogenital Development | 1921 External Genital Development | 1927 Female Foetus 15 cm | 1943 Testes Descent | Historic Disclaimer|
Some Recent Findings
|More recent papers|
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
G David Poznik, Yali Xue, Fernando L Mendez, Thomas F Willems, Andrea Massaia, Melissa A Wilson Sayres, Qasim Ayub, Shane A McCarthy, Apurva Narechania, Seva Kashin, Yuan Chen, Ruby Banerjee, Juan L Rodriguez-Flores, Maria Cerezo, Haojing Shao, Melissa Gymrek, Ankit Malhotra, Sandra Louzada, Rob Desalle, Graham R S Ritchie, Eliza Cerveira, Tomas W Fitzgerald, Erik Garrison, Anthony Marcketta, David Mittelman, Mallory Romanovitch, Chengsheng Zhang, Xiangqun Zheng-Bradley, Gonçalo R Abecasis, Steven A McCarroll, Paul Flicek, Peter A Underhill, Lachlan Coin, Daniel R Zerbino, Fengtang Yang, Charles Lee, Laura Clarke, Adam Auton, Yaniv Erlich, Robert E Handsaker, 1000 Genomes Project Consortium, Carlos D Bustamante, Chris Tyler-Smith Punctuated bursts in human male demography inferred from 1,244 worldwide Y-chromosome sequences. Nat. Genet.: 2016; PubMed 27111036
Izabela Szczerbal, Joanna Nowacka-Woszuk, Stanislaw Dzimira, Wojciech Atamaniuk, Wojciech Nizanski, Marek Switonski A Rare Case of Testicular Disorder of Sex Development in a Dog (78,XX; SRY-Negative) with Male External Genitalia and Detection of Copy Number Variation in the Region Upstream of the SOX9 Gene. Sex Dev: 2016; PubMed 27089505
Enver Şimşek, Çiğdem Binay, Meliha Demiral, Baran Tokar, Sare Kabukcuoğlu, Melek Üstün Gonadoblastoma and papillary tubal hyperplasia in ovotesticular syndrome. J Clin Res Pediatr Endocrinol: 2016; PubMed 27087521
N Rodrigues, Y Vuille, A Brelsford, J Merilä, N Perrin The genetic contribution to sex determination and number of sex chromosomes vary among populations of common frogs (Rana temporaria). Heredity (Edinb): 2016; PubMed 27071845
C A G Pellegrino, F Morotti, R M Untura, J H F Pontes, M F O Pellegrino, J P Campolina, M M Seneda, F A Barbosa, M Henry Use of sexed sorted semen for fixed-time artificial insemination or fixed-time embryo transfer of in vitro-produced embryos in cattle. Theriogenology: 2016; PubMed 27068357
- 1916 - Bridges describes the sex chromosomes of Drosophila melanogaster and shows that sex is determined by the X:autosome ratio
- 1923 - Painter describes the Sex chromosomes in mammals - it is assumed that sex determining mechanism will be the same as Drosophila
- 1959 - Ford et al. find a human XO and female - Turner's syndrome
- 1959 - Jacobs and Strong find an XXY male - Kleinfelter's syndrome
- together these prove that the Y chromosome determines sex and not the X:autosome ratio
- 1989 XX males found that carry a very small portion of Y chromosomal DNA (60kb)
- using DNA from these males a search for the testis determining gene, TDF or TDY led to the isolation of the gene
- gene called SRY because it comes from the Sex-determining Region of the Y chromosome. It is the molecular "switch" that determines sex in humans
Y Chromosome Genes
- Links: OMIM - acetylserotonin O-methyltransferase-like | OMIM - heat shock transcription factor, Y-linked 1 | OMIM - testis-specific transcript, Y-linked 5 | OMIM - sprouty homolog 3 (Drosophila)
Male Sex Determination
Sry (sex-determining region on the Y chromosome) gene was found in 1990 on the Y chromosome and the first Sox gene identified, the sry gene encodes a "testis-determining factor" a 204aa protein (Mr 23884 Da).
Sry acts as a transcriptional activator (HMG type-high mobility group) binding to DNA and initiating male sex determination then regulating male development. The protein sequence is shown on this current page and the full genebank entry can also be seen. The sry protein has a HMG box that binds DNA by intercalating in the minor groove. Read about the mapping of the testis determining factor which is SRY.
The actual gene targets of SRY are still being determined but at least one downstream gene Sox9 has been identified. Another gene Dax1 (nuclear hormone-receptor superfamily member) when expressed as a transgene will antagonize Sry and also force dosage-sensitive sex reversal.
Sox is an acronym of "Sry-related HMG box" and there have now been identified at least eight groups of genes that belong to this family with different functions. (for review see) The "HMG box" is a region that functions for DNA binding, DNA bending, protein interactions, and nuclear import or export.
The high mobility group (HMG) domain is a 79 amino acid protein region.
SRY Nuclear Import
A model for nuclear import of SRY from normal males and XY females. 
The distinct nuclear localization signals (NLSs) of SRY use different import pathways.
- cNLS - recognized by IMPβ, docks the transport complex at the nuclear pore complex (NPC) and is then translocation through. After nuclear entry of the complex, RanGTP binds to IMPβ to trigger release of SRY; DNA binding by SRY may also facilitate the release process.
- nNLS - mediates nuclear import through a novel pathway not utilizing conventional nuclear import factors such as IMPs but an unidentified "transport factor" (TF) suggested to be calcium-calmodulin.
Sry Target Genes
Cerebellin 4 precursor (Cbln4) - encodes a secreted protein expressed in Sertoli cells in the developing gonad.
Androgen receptor - SRY interacts with and negatively regulates this receptor transcriptional activity.
Testis-specific Protein Y Chromosome
Testis-specific Protein Y Chromosome (TSPY) is an ampliconic gene on the Y chromosome with an unknown function, though the protein that has been shown to interact with gonadoblastoma. A recent study suggests that TSPY serves as a repressor in androgen-induced tumor development in testicular germ-cell tumours (TGCTs).
|These are two intervals of sequence identity at the tips of both the Y and X chromosomes, the human pseudoautosomal regions PAR1 and PAR2. Loss of PAR1 has been associated with male sterility.|
- Monte E Turner, Carey Martin, Almir S Martins, Jeffrey Dunmire, Joel Farkas, Daniel L Ely, Amy Milsted Genomic and expression analysis of multiple Sry loci from a single Rattus norvegicus Y chromosome. BMC Genet.: 2007, 8;11 PubMed 17408480 | PMC1852568 | BMC Genet.
- C B Bridges Non-Disjunction as Proof of the Chromosome Theory of Heredity. Genetics: 1916, 1(1);1-52 PubMed 17245850 | PDF
- C B Bridges Non-Disjunction as Proof of the Chromosome Theory of Heredity (Concluded). Genetics: 1916, 1(2);107-63 PubMed 17245853 | PDF
- T S Painter FURTHER OBSERVATIONS ON THE SEX CHROMOSOMES OF MAMMALS. Science: 1923, 58(1500);247-8 PubMed 17748214 | Science
- C E FORD, K W JONES, P E POLANI, J C DE ALMEIDA, J H BRIGGS A sex-chromosome anomaly in a case of gonadal dysgenesis (Turner's syndrome). Lancet: 1959, 1(7075);711-3 PubMed 13642858
- P A JACOBS, J A STRONG A case of human intersexuality having a possible XXY sex-determining mechanism. Nature: 1959, 183(4657);302-3 PubMed 13632697
- Véronique Lefebvre, Bogdan Dumitriu, Alfredo Penzo-Méndez, Yu Han, Bhattaram Pallavi Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors. Int. J. Biochem. Cell Biol.: 2007, 39(12);2195-214 PubMed 17625949
- Vincent R Harley, Sharon Layfield, Claire L Mitchell, Jade K Forwood, Anna P John, Lyndall J Briggs, Sharon G McDowall, David A Jans Defective importin beta recognition and nuclear import of the sex-determining factor SRY are associated with XY sex-reversing mutations. Proc. Natl. Acad. Sci. U.S.A.: 2003, 100(12);7045-50 PubMed 12764225 | PMC165827 | Proc Natl Acad Sci U S A.
- Stephen T Bradford, Ryuji Hiramatsu, Madhavi P Maddugoda, Pascal Bernard, Marie-Christine Chaboissier, Andrew Sinclair, Andreas Schedl, Vincent Harley, Yoshiakira Kanai, Peter Koopman, Dagmar Wilhelm The cerebellin 4 precursor gene is a direct target of SRY and SOX9 in mice. Biol. Reprod.: 2009, 80(6);1178-88 PubMed 19211811 | PMC2804802 | Biol Reprod.
- X Yuan, M L Lu, T Li, S P Balk SRY interacts with and negatively regulates androgen receptor transcriptional activity. J. Biol. Chem.: 2001, 276(49);46647-54 PubMed 11585838
- Chihiro Akimoto, Takashi Ueda, Kazuki Inoue, Ikuko Yamaoka, Matomo Sakari, Wataru Obara, Tomoaki Fujioka, Akira Nagahara, Norio Nonomura, Syuichi Tsutsumi, Hiroyuki Aburatani, Tsuneharu Miki, Takahiro Matsumoto, Hirochika Kitagawa, Shigeaki Kato Testis-specific protein on Y chromosome (TSPY) represses the activity of the androgen receptor in androgen-dependent testicular germ-cell tumors. Proc. Natl. Acad. Sci. U.S.A.: 2010, 107(46);19891-6 PubMed 21041627
- Antonia Flaquer, Gudrun A Rappold, Thomas F Wienker, Christine Fischer The human pseudoautosomal regions: a review for genetic epidemiologists. Eur. J. Hum. Genet.: 2008, 16(7);771-9 PubMed 18398439
Ryohei Sekido SRY: A transcriptional activator of mammalian testis determination. Int. J. Biochem. Cell Biol.: 2010, 42(3);417-20 PubMed 20005972
Néstor O Bianchi Y chromosome structural and functional changes in human malignant diseases. Mutat. Res.: 2008, 682(1);21-7 PubMed 19699459
E C Osborne, M Lynch, R McLachlan, A O Trounson, D S Cram Microarray detection of Y chromosome deletions associated with male infertility. Reprod. Biomed. Online: 2007, 15(6);673-80 PubMed 18062864
Dagmar Wilhelm, Stephen Palmer, Peter Koopman Sex determination and gonadal development in mammals. Physiol. Rev.: 2007, 87(1);1-28 PubMed 17237341
Peter Koopman Sex determination: a tale of two Sox genes. Trends Genet.: 2005, 21(7);367-70 PubMed 15949865
A Antonelli, L Marcucci, R Elli, N Tanzi, D Paoli, A Radicioni, F Lombardo, A Lenzi, L Gandini Semen quality in men with Y chromosome aberrations. Int. J. Androl.: 2011, 34(5 Pt 1);453-60 PubMed 21039604
P Koopman, J Gubbay, N Vivian, P Goodfellow, R Lovell-Badge Male development of chromosomally female mice transgenic for Sry. Nature: 1991, 351(6322);117-21 PubMed 2030730
A H Sinclair, P Berta, M S Palmer, J R Hawkins, B L Griffiths, M J Smith, J W Foster, A M Frischauf, R Lovell-Badge, P N Goodfellow A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature: 1990, 346(6281);240-4 PubMed 1695712
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Cite this page: Hill, M.A. (2016) Embryology Y Chromosome. Retrieved April 28, 2016, from https://embryology.med.unsw.edu.au/embryology/index.php/Y_Chromosome
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