Y Chromosome

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Introduction

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]

Male


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
Genital Links: genital | Lecture - Medicine | Lecture - Science | Lecture Movie | Medicine - Practical | primordial germ cell | meiosis | Female | X | ovary | oocyte | uterus | vagina | reproductive cycles | menstrual cycle | Male | Y | testis | spermatozoa | penis | prostate | endocrine gonad‎ | Genital Movies | genital abnormalities | Assisted Reproductive Technology | puberty | Category:Genital
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
  • Alterations of sex determination pathway in the genital ridges of males with limited Y chromosome genes[2] "We previously demonstrated that in the mouse only two Y chromosome genes are required for a male to produce an offspring with the help of assisted reproduction technologies (ART): testis determinant Sry and spermatogonial proliferation factor Eif2s3y. Subsequently, we have shown that the function of these genes can be replaced by transgenic overexpression of their homologues, autosomally encoded Sox9 and X-chromosome encoded Eif2s3x. Males with Y chromosome contribution limited to two (XEif2s3yOSry), one (XEif2s3yOSox9 and XOSry, Eif2s3x) and no genes (XOSox9, Eif2s3x) produced haploid germ cells and sired offspring after ART. However, despite successful assisted reproductive outcome, they had smaller testes and displayed abnormal development of the seminiferous epithelium and testicular interstitium. Here we explored whether these testicular defects originated from altered pro-testis and pro-ovary factor signaling in genital ridges at the time of sex determination."
  • Dual nuclear import mechanisms of sex determining factor SRY: intracellular Ca2+ as a switch [3] "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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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

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.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Y Chromosome

Cécile Courret, Pierre R Gérard, David Ogereau, Matthieu Falque, Laurence Moreau, Catherine Montchamp-Moreau X-chromosome meiotic drive in Drosophila simulans: a QTL approach reveals the complex polygenic determinism of Paris drive suppression. Heredity (Edinb): 2018; PubMed 30518968

Suzanna C Francis, Christian Holm Hansen, Julia Irani, Aura Andreasen, Kathy Baisley, Vicky Jespers, Tania Crucitti, John Changalucha, Richard J Hayes, Soori Nnko, Deborah Watson-Jones, Anne Buvé Results from a cross-sectional sexual and reproductive health study among school girls in Tanzania: high prevalence of bacterial vaginosis. Sex Transm Infect: 2018; PubMed 30518620

Rafał Parada, Magdalena Kawka, Mariusz Sacharczuk, Paweł Urbański, Kazimierz Jaszczak Cytogenetic and genetic study of a Y-linked microsatellite polymorphism in Polish Black-and-White cattle breed. Saudi J Biol Sci: 2018, 25(7);1406-1410 PubMed 30505189

Cemal Ekici, Zeynep Esener, Selcen Korkmaz, Nihal Saltürk, Sengul Yüksel, Ahmet Koç A Rare Mosaic Karyotype of 45,X/46,X,psu idic(Y)(p11.32)/46,XY with SHOX Haploinsufficiency, External Male Genitalia, and Short Stature. Sex Dev: 2018; PubMed 30504706

Li Li, Xiaoyan You, Mingxia Zhong, Lei Wang, Weizhe Li, Zhaoshu Zeng [Study of genetic polymorphisms of 7 Y chromosome single nucleotide polymorphism loci among Mongolians from Inner Mongolia Region]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi: 2018, 35(6);901-903 PubMed 30512175


Search term: SRY

Cemal Ekici, Zeynep Esener, Selcen Korkmaz, Nihal Saltürk, Sengul Yüksel, Ahmet Koç A Rare Mosaic Karyotype of 45,X/46,X,psu idic(Y)(p11.32)/46,XY with SHOX Haploinsufficiency, External Male Genitalia, and Short Stature. Sex Dev: 2018; PubMed 30504706

Umesh Tharehalli, Michael Svinarenko, Johann M Kraus, Silke D Kühlwein, Robin Szekely, Ute Kiesle, Annika Scheffold, Thomas F E Barth, Alexander Kleger, Reinhold Schirmbeck, Hans A Kestler, Thomas Seufferlein, Franz Oswald, Sarah-Fee Katz, André Lechel ##Title## Int J Mol Sci: 2018, 19(12); PubMed 30501048

Zhi Liu, Yang Zhong, Yu Jian Chen, Hui Chen SOX11 regulates apoptosis and cell cycle in hepatocellular carcinoma via Wnt/β-catenin signaling pathway. Biotechnol. Appl. Biochem.: 2018; PubMed 30517979

Xuejiao Chen, Meizhen Dai, Ying Zhu, Zhehang He, Yang Zhang, Yihong Pan, Weiwu Shi [Genetic study of a fetus with a de novo Xp22.33;Yp11.2 translocation]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi: 2018, 35(6);868-871 PubMed 30512166

Shengfang Qin, Xueyan Wang, Yunxing Li [Genetic analysis of a 46,XY female with sex reversal due to duplication of NR0B1 gene]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi: 2018, 35(6);804-807 PubMed 30512150

History

  • 1916 - Bridges[4][5] describes the sex chromosomes of Drosophila melanogaster and shows that sex is determined by the X:autosome ratio
  • 1923 - Painter[6] describes the Sex chromosomes in mammals - it is assumed that sex determining mechanism will be the same as Drosophila
  • 1959 - Ford et al.[7] find a human XO and female - Turner's syndrome
  • 1959 - Jacobs and Strong[8] 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


  • ZFY (Yp11.2) zinc finger transcription factor, required in males for spermatozoa or testis maturation.[9] A similar sequence called ZFX, has been identified on the X chromosome, that in humans escapes X inactivation.


Links: ZFY | 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

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[10]


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

SOX

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[11]) 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
Symbol
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.[12]

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.[13]

Androgen receptor - SRY interacts with and negatively regulates this receptor transcriptional activity.[14]

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).[15]

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.[16] Loss of PAR1 has been associated with male sterility.

References

  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. Ortega EA, Salvador Q, Fernandez M & Ward MA. (2018). Alterations of sex determination pathway in the genital ridges of males with limited Y chromosome genes. Biol. Reprod. , , . PMID: 30285093 DOI.
  3. 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.
  4. Bridges CB. (1916). Non-Disjunction as Proof of the Chromosome Theory of Heredity. Genetics , 1, 1-52. PMID: 17245850
  5. Bridges CB. (1916). Non-Disjunction as Proof of the Chromosome Theory of Heredity (Concluded). Genetics , 1, 107-63. PMID: 17245853
  6. Painter TS. (1923). FURTHER OBSERVATIONS ON THE SEX CHROMOSOMES OF MAMMALS. Science , 58, 247-8. PMID: 17748214 DOI.
  7. 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
  8. JACOBS PA & STRONG JA. (1959). A case of human intersexuality having a possible XXY sex-determining mechanism. Nature , 183, 302-3. PMID: 13632697
  9. Grants J, Flanagan E, Yee A & Romaniuk PJ. (2010). Characterization of the DNA binding activity of the ZFY zinc finger domain. Biochemistry , 49, 679-86. PMID: 20028140 DOI.
  10. de Lau WB, Snel B & Clevers HC. (2012). The R-spondin protein family. Genome Biol. , 13, 242. PMID: 22439850 DOI.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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

Reviews

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.

Articles

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, December 11) Embryology Y Chromosome. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Y_Chromosome

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