Y Chromosome

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Human Y chromosome showing SRY region
Human Y chromosome showing SRY region

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.[1]


Placental male mammals have SRY protein transcription factor that activates Sox9 for testes formation. SRY evolved as a hybrid gene of Dgcr8 expressed in the developing placenta and Sox3 expressed in hypothalamic development.

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:

  1. X-transposed - 3-4 Ma transposition 99% identical to human Xq21
  2. X-degenerate - 14 single copy or 13 pseudogene homologs of X-linked genes
  3. ampliconic sequences - Sequences with strong identity to other regions of Y

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)

Y Chromosome Links: Y Chromosome | Genital - Male Development | Epigenetics | X Chromosome | Category:Y Chromosome
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Historic Embryology - Genital 
1901 Urinogenital Tract | 1902 The Uro-Genital System | 1904 Ovary and Testis | 1904 Leydig Cells | 1904 Hymen | 1905 Testis vascular | 1909 Prostate | 1912 Prostate | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1914 Female | 1915 Cowper’s and Bartholin’s Glands | 1920 Wolffian tubules | 1921 Urogenital Development | 1921 External Genital | 1927 Female Foetus 15 cm | 1932 Postnatal Ovary | 1935 Prepuce | 1935 Wolffian Duct | 1942 Sex Cords | 1943 Testes Descent | 1953 Germ Cells | Historic Embryology Papers | Historic Disclaimer
Human Chromosomes: 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | X | Y  

Human idiogram.jpg

Human idiogram

Some Recent Findings

X and Y chromosomes
  • Dual nuclear import mechanisms of sex determining factor SRY: intracellular Ca2+ as a switch [2] "The sex-determining region on the Y chromosome (SRY) has 2 nuclear localization signals (NLSs) that flank the DNA binding high mobility group (HMG) domain; the β-NLS and the CaM-NLS, which mediate nuclear transport through importin β1 (Impβ1) and the calcium-binding protein calmodulin (CaM), respectively. ...The results imply mutual exclusivity of nuclear transport via the 2 NLSs with intracellular Ca(2+) as the switch between the 2.-Kaur, G. Jans, D. A. Dual nuclear import mechanisms of sex determining factor SRY: intracellular Ca(2+) as a switch."
More recent papers  
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Search term: Y Chromosome

C Cuman, C E Beyer, D Brodie, T Fullston, J I Lin, E Willats, D Zander-Fox, J Mullen Defining the limits of detection for chromosome rearrangements in the preimplantation embryo using next generation sequencing. Hum. Reprod.: 2018; PubMed 30007310

Elenice M Alvarenga, Carlos H L Imperador, Vanessa B Bardella, Vera L C C Rodrigues, Mateus Mondin, Diogo C Cabral-de-Mello, Alberto S Moraes, Maria Luiza S Mello Histone acetylation and methylation marks in chromatin of Panstrongylus megistus (Hemiptera, Reduviidae). Acta Histochem.: 2018; PubMed 30005894

Andrea Sala, Mariela Caputo, Santiago Ginart, Graciela Theiler, María Laura Parolin, Raúl Francisco Carnese, Leonardo Fainboim, Daniel Corach Historical records under the genetic evidence: "Chiriguano" tribe genesis as a test case. Mol. Biol. Rep.: 2018; PubMed 30003508

Tom E C Kieffer, Anne Laskewitz, Marijke M Faas, Sicco A Scherjon, Jan Jaap H M Erwich, Sanne J Gordijn, Jelmer R Prins ##Title## J Immunol Res: 2018, 2018;1950879 PubMed 30003112

Hironaga Kakoi, Mio Kikuchi, Teruaki Tozaki, Kei-Ichi Hirota, Shun-Ichi Nagata, Seiji Hobo, Masaki Takasu Distribution of Y chromosomal haplotypes in Japanese native horse populations. J Equine Sci: 2018, 29(2);39-42 PubMed 29991921

Search term: SRY

Xin Ma, Xue Lv, Hong-Yan Liu, Xing Wu, Li Wang, Hao Li, Hai-Yan Chou Genetic diagnosis for X-linked hypohidrotic ectodermal dysplasia family with a novel Ectodysplasin A gene mutation. J. Clin. Lab. Anal.: 2018;e22593 PubMed 30006944

Jing-Dong Zhou, Yu-Xin Wang, Ting-Juan Zhang, Xi-Xi Li, Yu Gu, Wei Zhang, Ji-Chun Ma, Jiang Lin, Jun Qian ##Title## Clin Epigenetics: 2018, 10;92 PubMed 30002740

Yu Zhang, Yubin Pan, Chunyuan Xie, Yan Zhang miR-34a exerts as a key regulator in the dedifferentiation of osteosarcoma via PAI-1-Sox2 axis. Cell Death Dis: 2018, 9(7);777 PubMed 29991717

Lu Li, Wen-Ting Yang, Peng-Sheng Zheng, Xiao-Fang Liu SOX17 restrains proliferation and tumor formation by down-regulating activity of the Wnt/β-catenin signaling pathway via trans-suppressing β-catenin in cervical cancer. Cell Death Dis: 2018, 9(7);741 PubMed 29970906

Lu Wang, Yu Fan, Lian Zhang, Lili Li, Guanyu Kuang, Cheng Luo, Chen Li, Tingxiu Xiang, Qian Tao, Qian Zhang, Jianming Ying Classic SRY-box protein SOX7 functions as a tumor suppressor regulating WNT signaling and is methylated in renal cell carcinoma. FASEB J.: 2018;fj201701453RR PubMed 29957056


  • 1916 - Bridges[3][4] describes the sex chromosomes of Drosophila melanogaster and shows that sex is determined by the X:autosome ratio
  • 1923 - Painter[5] describes the Sex chromosomes in mammals - it is assumed that sex determining mechanism will be the same as Drosophila
  • 1959 - Ford et al.[6] find a human XO and female - Turner's syndrome
  • 1959 - Jacobs and Strong[7] 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

Human Y chromosome 01.jpg

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)

Human Y chromosome


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.

Mouse sex determination genes 01.jpg

Mouse sex determination genes[8]

Links: OMIM - Sry | 3d Structure Of The Human Sry-Dna Complex


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[9]) 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.

Human SOX Family  
Table - Human Sox Family
Approved Name Previous Symbols Synonyms Chromosome
SOX1 SRY-box 1 13q34
SOX2 SRY-box 2 3q26.33
SOX3 SRY-box 3 PHP Xq27.1
SOX4 SRY-box 4 6p22.3
SOX5 SRY-box 5 "L-SOX5, MGC35153" 12p12.1
SOX6 SRY-box 6 11p15.3
SOX7 SRY-box 7 8p23.1
SOX8 SRY-box 8 16p13.3
SOX9 SRY-box 9 "CMD1, CMPD1" SRA1 17q24.3
SOX10 SRY-box 10 "DOM, WS4, WS2E" 22q13.1
SOX11 SRY-box 11 2p25.2
SOX12 SRY-box 12 SOX22 20p13
SOX13 SRY-box 13 "Sox-13, ICA12, MGC117216" 1q32.1
SOX14 SRY-box 14 SOX28 3q22.3
SOX15 SRY-box 15 SOX20 "SOX27, SOX26" 17p13.1
SOX17 SRY-box 17 8q11.23
SOX18 SRY-box 18 20q13.33
SOX21 SRY-box 21 SOX25 13q32.1
SOX30 SRY-box 30 5q33.3
SRY sex determining region Y TDF Yp11.2
    Links: Developmental Signals - Sox | OMIM | HGNC | Tbx Family | Bmp Family | Fgf Family | Pax Family | R-spondin Family | Sox Family | Tbx Family

SRY Nuclear Import

SRY nuclear import model.jpg

A model for nuclear import of SRY from normal males and XY females.[10]

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.[11]

Androgen receptor - SRY interacts with and negatively regulates this receptor transcriptional activity.[12]

Testis-specific Protein Y Chromosome

Testis-specific protein on 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).[13]

Pseudoautosomal Regions

Sex chromosomes pseudoautosomal regions. These are two intervals of sequence identity at the tips of both the Y and X chromosomes, the human pseudoautosomal regions PAR1 and PAR2.[14] Loss of PAR1 has been associated with male sterility.


  1. Turner ME, Martin C, Martins AS, Dunmire J, Farkas J, Ely DL & Milsted A. (2007). Genomic and expression analysis of multiple Sry loci from a single Rattus norvegicus Y chromosome. BMC Genet. , 8, 11. PMID: 17408480 DOI.
  2. Kaur G & Jans DA. (2011). Dual nuclear import mechanisms of sex determining factor SRY: intracellular Ca2+ as a switch. FASEB J. , 25, 665-75. PMID: 21051653 DOI.
  3. Bridges CB. (1916). Non-Disjunction as Proof of the Chromosome Theory of Heredity. Genetics , 1, 1-52. PMID: 17245850
  4. Bridges CB. (1916). Non-Disjunction as Proof of the Chromosome Theory of Heredity (Concluded). Genetics , 1, 107-63. PMID: 17245853
  5. Painter TS. (1923). FURTHER OBSERVATIONS ON THE SEX CHROMOSOMES OF MAMMALS. Science , 58, 247-8. PMID: 17748214 DOI.
  6. FORD CE, JONES KW, POLANI PE, DE ALMEIDA JC & BRIGGS JH. (1959). A sex-chromosome anomaly in a case of gonadal dysgenesis (Turner's syndrome). Lancet , 1, 711-3. PMID: 13642858
  7. JACOBS PA & STRONG JA. (1959). A case of human intersexuality having a possible XXY sex-determining mechanism. Nature , 183, 302-3. PMID: 13632697
  8. de Lau WB, Snel B & Clevers HC. (2012). The R-spondin protein family. Genome Biol. , 13, 242. PMID: 22439850 DOI.
  9. Lefebvre V, Dumitriu B, Penzo-Méndez A, Han Y & Pallavi B. (2007). Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors. Int. J. Biochem. Cell Biol. , 39, 2195-214. PMID: 17625949 DOI.
  10. Harley VR, Layfield S, Mitchell CL, Forwood JK, John AP, Briggs LJ, McDowall SG & Jans DA. (2003). 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. , 100, 7045-50. PMID: 12764225 DOI.
  11. Bradford ST, Hiramatsu R, Maddugoda MP, Bernard P, Chaboissier MC, Sinclair A, Schedl A, Harley V, Kanai Y, Koopman P & Wilhelm D. (2009). The cerebellin 4 precursor gene is a direct target of SRY and SOX9 in mice. Biol. Reprod. , 80, 1178-88. PMID: 19211811 DOI.
  12. Yuan X, Lu ML, Li T & Balk SP. (2001). SRY interacts with and negatively regulates androgen receptor transcriptional activity. J. Biol. Chem. , 276, 46647-54. PMID: 11585838 DOI.
  13. Akimoto C, Ueda T, Inoue K, Yamaoka I, Sakari M, Obara W, Fujioka T, Nagahara A, Nonomura N, Tsutsumi S, Aburatani H, Miki T, Matsumoto T, Kitagawa H & Kato S. (2010). 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. , 107, 19891-6. PMID: 21041627 DOI.
  14. Flaquer A, Rappold GA, Wienker TF & Fischer C. (2008). The human pseudoautosomal regions: a review for genetic epidemiologists. Eur. J. Hum. Genet. , 16, 771-9. PMID: 18398439 DOI.

Online Textbooks

Search NLM Online Textbooks "Y chromosome" : Developmental Biology | Endocrinology | Molecular Biology of the Cell | The Cell- A molecular Approach


Sekido R. (2010). SRY: A transcriptional activator of mammalian testis determination. Int. J. Biochem. Cell Biol. , 42, 417-20. PMID: 20005972 DOI.

Bianchi NO. (2009). Y chromosome structural and functional changes in human malignant diseases. Mutat. Res. , 682, 21-7. PMID: 19699459 DOI.

Osborne EC, Lynch M, McLachlan R, Trounson AO & Cram DS. (2007). Microarray detection of Y chromosome deletions associated with male infertility. Reprod. Biomed. Online , 15, 673-80. PMID: 18062864

Wilhelm D, Palmer S & Koopman P. (2007). Sex determination and gonadal development in mammals. Physiol. Rev. , 87, 1-28. PMID: 17237341 DOI.

Koopman P. (2005). Sex determination: a tale of two Sox genes. Trends Genet. , 21, 367-70. PMID: 15949865 DOI.


Antonelli A, Marcucci L, Elli R, Tanzi N, Paoli D, Radicioni A, Lombardo F, Lenzi A & Gandini L. (2011). Semen quality in men with Y chromosome aberrations. Int. J. Androl. , 34, 453-60. PMID: 21039604 DOI.

Koopman P, Gubbay J, Vivian N, Goodfellow P & Lovell-Badge R. (1991). Male development of chromosomally female mice transgenic for Sry. Nature , 351, 117-21. PMID: 2030730 DOI.

Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, Foster JW, Frischauf AM, Lovell-Badge R & Goodfellow PN. (1990). A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature , 346, 240-4. PMID: 1695712 DOI.

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Cite this page: Hill, M.A. (2018, July 15) Embryology Y Chromosome. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Y_Chromosome

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