H-Y antigen

anti-Müllerian hormone
Identifiers
SymbolAMH
NCBI gene268
HGNC464
OMIM600957
RefSeqNM_000479
UniProtP03971
Other data
LocusChr. 19 p13.3
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StructuresSwiss-model
DomainsInterPro
Lysine-Specific Demethylase 5D protein
Identifiers
SymbolKDM5D
Alt. symbolsHYA, SMCY
HGNC11115
OMIM426000
RefSeqNM_004653
UniProtQ9BY66
Other data
LocusChr. Y q11.223
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StructuresSwiss-model
DomainsInterPro
Male Enhanced Antigen 1
Identifiers
SymbolMEA1
Alt. symbolsHYS
HGNC6986
OMIM143170
RefSeqNM_001318942
UniProtQ16626
Other data
LocusChr. 6 p21.1
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StructuresSwiss-model
DomainsInterPro

H-Y antigen is a male tissue specific antigen.[1] Originally thought to trigger the formation of testes (via loci, an autosomal gene that generates the antigen and one that generates the receptor)[2] it is now known that it does not trigger the formation of testes but may be activated by the formation of testes.[3]

There are several antigens which qualify as H-Y as defined by rejection of male skin grafts in female hosts or detected by cytotoxic T cells or antibodies. One H-Y, secreted by the testis, defined by antibodies, is identical to Müllerian-inhibiting substance (AMH gene).[1] Another H-Y, minor histocompatibility antigen, seemed to be encoded in the SMCY gene (acronym for 'selected mouse cDNA on Y'), later identified as an 11-residue peptide from the Lysine-Specific Demethylase 5D protein (KDM5D gene) presented by HLA-B7. A third example is MEA1.

Association with spermatogenesis

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It has been shown that male mice lacking in the H-Y antigen, hence lacking in the gene producing it, have also lost genetic information responsible for spermatogenesis.[4] This result also identified a gene on the mouse Y chromosome, distinct from the testis-determining gene, that was essential for spermatogenesis, thus raising the possibility that the very product of this "spermatogenesis gene" is the H-Y antigen.[4]

Male homosexuality and the birth order effect

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Among humans, it has been observed that men with more older brothers tend to have a higher chance of being homosexual (see Fraternal birth order and male sexual orientation). For every additional older brother, a man's chance of being homosexual can rise by up to 33%.[5] One theory to explain this involves H-Y antigens, which suggests that a maternal immune reaction to these antigens has, to an extent, an inhibitory effect on the masculinization of the brain, and therefore, the more male foetuses that the mother of a man has had, the greater the maternal immune response towards him[6] and thus the greater the inhibitory effect on brain masculinization, which is believed to be a factor in sexual orientation.[5]

This hypothesis is supported by evidence that older sisters have no discernible influence on the sexual orientation of later-born males, which would be expected since H-Y antigen is male tissue specific, the 'probable involvement of H-Y antigen in the development of sex-typical traits, and the detrimental effects of immunization of female mice to H-Y antigen on the reproductive performance of subsequent male offspring'.[7] More specifically, recent research (Jan 2018) has found maternal antibodies to the neuroligin NLGN4Y protein, a Y-chromosome protein important in male fetal brain development, to be involved in the fraternal birth order effect.[8]

References

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  1. ^ a b Müller U (June 1996). "H-Y antigens". Human Genetics. 97 (6): 701–4. doi:10.1007/BF02346175. PMID 8641682. S2CID 25641671.
  2. ^ "H-Y Antigen". mediLexicon. Wolters Kluwer. Archived from the original on 2017-11-30.
  3. ^ Wolf U (1998). "The serologically detected H-Y antigen revisited". Cytogenetics and Cell Genetics. 80 (1–4): 232–5. doi:10.1159/000014986. PMID 9678364. S2CID 25908189.
  4. ^ a b Burgoyne PS, Levy ER, McLaren A (1986). "Spermatogenic failure in male mice lacking H-Y antigen". Nature. 320 (6058): 170–2. Bibcode:1986Natur.320..170B. doi:10.1038/320170a0. PMID 3951555. S2CID 4284719.
  5. ^ a b Ridley M (2000). Genome: The Autobiography of a Species in 23 Chapters. Harper and Collins. ISBN 978-0-06-089408-5.
  6. ^ Dare T (8 October 2013). "Vaccination and immunity for iGCSE Biology". YouTube.
  7. ^ Blanchard R, Klassen P (April 1997). "H-Y antigen and homosexuality in men". Journal of Theoretical Biology. 185 (3): 373–8. Bibcode:1997JThBi.185..373B. CiteSeerX 10.1.1.602.8423. doi:10.1006/jtbi.1996.0315. PMID 9156085.
  8. ^ Bogaert AF, Skorska MN, Wang C, Gabrie J, MacNeil AJ, Hoffarth MR, VanderLaan DP, Zucker KJ, Blanchard R (January 2018). "Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y". Proceedings of the National Academy of Sciences of the United States of America. 115 (2): 302–306. Bibcode:2018PNAS..115..302B. doi:10.1073/pnas.1705895114. PMC 5777026. PMID 29229842.