Meiotic Sex Chromosome Inactivation

Abstract

The differentiation of sex chromosomes through evolution has resulted in significant loss of homology and gene content which has profound consequences on gene dosage between the sexes and impacts on their behaviour through meiosis. During spermatogenesis the unpaired DNA, of heteromorphic sex chromosomes becomes transcriptionally silenced and sequestered into a ‘sex body’, a process termed ‘meiotic sex chromosome inactivation’. This essential meiotic event involves an ordered hierarchy of epigenetic changes to the sex chromosome DNA initiated by conserved DNA damage, repair and checkpoint machinery. Although the reason for this repression remains unclear, it is thought to prevent recombination between nonhomologous sex chromosome DNA and to avoid stringent meiotic checkpoints. Recent work has extended our understanding of the evolutionary conservation of meiotic silencing to include the avian ZW sex chromosome system providing new insights into the evolutionary dynamics of meiotic sex chromosome organization in diverse species.

Key concepts:

  • The accumulation of mutation and rearrangements on sex chromosomes lead to blocks in recombination, accumulation of sexually antagonistic genes and the differential degradation of sex chromosomes.

  • Heteromorphic sex chromosomes result in gene dosage imbalance between the sexes and unsynapsed DNA in meiosis I.

  • Meiotic sex chromosome inactivation protects unpaired sex chromosome DNA from aberrant recombination and checkpoint surveillance machinery.

  • Sex chromosomes undergo transcriptional silencing during late prophase due to the accumulation of conserved epigenetic changes.

  • Therian mammals have active X‐borne retrogenes on autosomes to compensate for the loss of transcription of sex chromosome genes important for spermatogenesis.

Keywords: spermatogenesis; meiotic silencing; spigenetics; sex chromosomes

Figure 1.

Evolutionary perspective of sex chromosome systems. Figure indicates sex chromosome complements, current knowledge on MSCI, and identification of retrotransposon movements from the X chromosome. Question mark indicates current lack of knowledge on monotreme MSCI. Ma; million years ago.

Figure 2.

The synaptonemal complex mediates chromosomal synapsis at pachytene. Mouse pachytene spermatocyte immunostained using antibodies for synaptonemal complex protein 3 (SCP3) to visualize lateral elements of the condensed chromosomal axes (left panel) and synaptonemal complex protein 1 (SCP1) to visualize transverse filaments of the synapsed homologous regions (middle panel). The right panel shows the merged image with DAPI (4′,6′‐diamidino‐2‐phenylindole) in blue. Sex chromosomes appear green in the merged image (circled with broken line). Images produced by TJD.

Figure 3.

The sex body accumulates signature epigenetic modifications to effect transcriptional silencing of the sex chromosomes at pachytene. Image shows phosphorylation of H2AX (γH2AX) is concentrated on the sex chromatin at pachytene in a mouse spermatocyte. Text lists common modifications to sex chromatin during MSCI. Image produced by TJD.

Figure 4.

Comparative organizational behaviour of sex chromosomes in pachytene spermatocytes.

close

References

Aravin AA, Hannon GJ and Brennecke J (2007a) The Piwi‐piRNA pathway provides an adaptive defense in the transposon arms race. Science 318: 761–764.

Aravin AA, Sachidanandam R, Girard A, Fejes‐Toth K and Hannon GJ (2007b) Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316: 744–747.

Baarends WM, Wassenaar E, van der Laan R et al. (2005) Silencing of unpaired chromatin and histone H2A ubiquitination in mammalian meiosis. Molecular and Cellular Biology 25: 1041–1053.

Bininda‐Emonds OR, Cardillo M, Jones KE et al. (2007) The delayed rise of present‐day mammals. Nature 446: 507–512.

Bradley J, Baltus A, Skaletsky H et al. (2004) An X‐to‐autosome retrogene is required for spermatogenesis in mice. Nature Genetics 36: 872–876.

Brawand D, Wahli W and Kaessmann H (2008) Loss of egg yolk genes in mammals and the origin of lactation and placentation. PLoS Biology 6: e63.

Brennecke J, Aravin AA, Stark A et al. (2007) Discrete small RNA‐generating loci as master regulators of transposon activity in Drosophila. Cell 128: 1089–1103.

Emerson JJ, Kaessmann H, Betran E and Long M (2004) Extensive gene traffic on the mammalian X chromosome. Science 303: 537–540.

Fernandez‐Capetillo O, Mahadevaiah SK, Celeste A et al. (2003) H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis. Dev Cell 4: 497–508.

Franco MJ, Sciurano RB and Solari AJ (2007) Protein immunolocalization supports the presence of identical mechanisms of XY body formation in eutherians and marsupials. Chromosome Research 15: 815–824.

Graves JA (1991) Mammalian genome evolution: new clues from comparisons of eutherians, marsupials and monotremes. Comparative Biochemistry and Physiology. A 99: 5–11.

Grutzner F, Rens W, Tsend‐Ayush E et al. (2004) In the platypus a meiotic chain of ten sex chromosomes shares genes with the bird Z and mammal X chromosomes. Nature 432: 913–917.

Guo X, Su B, Zhou Z and Sha J (2009) Rapid evolution of mammalian X‐linked testis microRNAs. BMC Genomics 10: 97.

Hamer G, Roepers‐Gajadien HL, van Duyn‐Goedhart A et al. (2003) DNA double‐strand breaks and gamma‐H2AX signaling in the testis. Biol Reprod 68: 628–634.

Hammoud SS, Nix DA, Zhang H et al. (2009) Distinctive chromatin in human sperm packages genes for embryo development. Nature 460: 473–478.

Handel MA (2004) The XY body: a specialized meiotic chromatin domain. Experimental Cell Research 296: 57–63.

Hendriksen PJ, Hoogerbrugge JW, Themmen AP et al. (1995) Postmeiotic transcription of X and Y chromosomal genes during spermatogenesis in the mouse. Developmental Biology 170: 730–733.

Hornecker JL, Samollow PB, Robinson ES, Vandeberg JL and McCarrey JR (2007) Meiotic sex chromosome inactivation in the marsupial Monodelphis domestica. Genesis 45: 696–708.

Hoyer‐Fender S, Costanzi C and Pehrson JR (2000) Histone macroH2A1.2 is concentrated in the XY‐body by the early pachytene stage of spermatogenesis. Experimental Cell Research 258: 254–260.

International Chicken Genome Sequencing Consortium (2004) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432: 695–716.

Lachner M, O'Carroll D, Rea S, Mechtler K and Jenuwein T (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410: 116–120.

Lyon MF (1962) Sex chromatin and gene action in the mammalian X‐chromosome. American Journal of Human Genetics 14: 135–148.

Mahadevaiah SK, Turner JM, Baudat F et al. (2001) Recombinational DNA double‐strand breaks in mice precede synapsis. Nature Genetics 27: 271–276.

Mank JE and Ellegren H (2009) Sex‐linkage of sexually antagonistic genes is predicted by female, but not male, effects in birds. Evolution 63: 1464–1472.

Marcon E, Babak T, Chua G, Hughes T and Moens PB (2008) miRNA and piRNA localization in the male mammalian meiotic nucleus. Chromosome Research 16: 243–260.

Marques AC, Dupanloup I, Vinckenbosch N, Reymond A and Kaessmann H (2005) Emergence of young human genes after a burst of retroposition in primates. PLoS Biology 3: e357.

McKee BD and Handel MA (1993) Sex chromosomes, recombination, and chromatin conformation. Chromosoma 102: 71–80.

Mueller JL, Mahadevaiah SK, Park PJ et al. (2008) The mouse X chromosome is enriched for multicopy testis genes showing postmeiotic expression. Nature Genetics 40: 794–799.

Murchison EP, Kheradpour P, Sachidanandam R et al. (2008) Conservation of small RNA pathways in platypus. Genome Research 18: 995–1004.

Namekawa SH, Park PJ, Zhang LF et al. (2006) Postmeiotic sex chromatin in the male germline of mice. Current Biology 16: 660–667.

Namekawa SH, VandeBerg JL, McCarrey JR and Lee JT (2007) Sex chromosome silencing in the marsupial male germ line. Proceedings of the National Academy of Sciences of the USA 104: 9730–9735.

Nur U (1981) Undercondensation and localized euchromatinization of the x chromosome in the grasshopper Melanoplus femur‐rubrum. Chromosoma 82: 353–365.

Ohno S and Cattanach BM (1962) Cytological study of an X‐autosome translocation in Mus musculus. Cytogenetics 1: 129–140.

Okamoto I, Arnaud D, Le Baccon P et al. (2005) Evidence for de novo imprinted X‐chromosome inactivation independent of meiotic inactivation in mice. Nature 438: 369–373.

Page J, Berrios S, Rufas JS et al. (2003) The pairing of X and Y chromosomes during meiotic prophase in the marsupial species Thylamys elegans is maintained by a dense plate developed from their axial elements. Journal of Cell Sciences 116: 551–560.

Page J, Viera A, Parra MT et al. (2006) Involvement of synaptonemal complex proteins in sex chromosome segregation during marsupial male meiosis. PLoS Genetics 2: e136.

Potrzebowski L, Vinckenbosch N, Marques AC et al. (2008) Chromosomal gene movements reflect the recent origin and biology of therian sex chromosomes. PLoS Biology 6: e80.

Rens W, O'Brien PC, Grutzner F et al. (2007) The multiple sex chromosomes of platypus and echidna are not completely identical and several share homology with the avian Z. Genome Biology 8: R243.

Rohozinski J and Bishop CE (2004) The mouse juvenile spermatogonial depletion (jsd) phenotype is due to a mutation in the X‐derived retrogene, mUtp14b. Proceedings of the National Academy of Sciences of the USA 101: 11695–11700.

Schoenmakers S, Wassenaar E, Hoogerbrugge JW et al. (2009) Female meiotic sex chromosome inactivation in chicken. PLoS Genetics 5: e1000466.

Sharp P (1982) Sex chromosome pairing during male meiosis in marsupials. Chromosoma 86: 27–47.

Shiu PK, Raju NB, Zickler D and Metzenberg RL (2001) Meiotic silencing by unpaired DNA. Cell 107: 905–916.

Solari AJ (1974) The behavior of the XY pair in mammals. International Review of Cytology 38: 273–317.

Solari AJ (1992) Equalization of Z and W axes in chicken and quail oocytes. Cytogenetics and Cell Genetics 59: 52–56.

Solari AJ and Moses MJ (1977) Synaptonemal complexes in a tetraploid mouse spermatocyte. Experimental Cell Research 108: 464–467.

Song R, Ro S, Michaels JD et al. (2009) Many X‐linked microRNAs escape meiotic sex chromosome inactivation. Nature Genetics 41: 488–493.

Turner JM (2007) Meiotic sex chromosome inactivation. Development 134: 1823–1831.

Turner JM, Aprelikova O, Xu X et al. (2004) BRCA1, histone H2AX phosphorylation, and male meiotic sex chromosome inactivation. Current Biology 14: 2135–2142.

Turner JM, Mahadevaiah SK, Ellis PJ, Mitchell MJ and Burgoyne PS (2006) Pachytene asynapsis drives meiotic sex chromosome inactivation and leads to substantial postmeiotic repression in spermatids. Developmental Cell 10: 521–529.

Turner JM, Mahadevaiah SK, Fernandez‐Capetillo O et al. (2005) Silencing of unsynapsed meiotic chromosomes in the mouse. Nature Genetics 37: 41–47.

Veyrunes F, Waters PD, Miethke P et al. (2008) Bird‐like sex chromosomes of platypus imply recent origin of mammal sex chromosomes. Genome Research 18: 965–973.

Wang PJ (2004) X chromosomes, retrogenes and their role in male reproduction. Trends in Endocrinology and Metabolism 15: 79–83.

Wang PJ, McCarrey JR, Yang F and Page DC (2001) An abundance of X‐linked genes expressed in spermatogonia. Nature Genetics 27: 422–426.

Wang PJ, Page DC and McCarrey JR (2005) Differential expression of sex‐linked and autosomal germ‐cell‐specific genes during spermatogenesis in the mouse. Human Molecular Genetics 14: 2911–2918.

Warren WC, Hillier LW, Marshall Graves JA et al. (2008) Genome analysis of the platypus reveals unique signatures of evolution. Nature 453: 175–183.

Watanabe T, Takeda A, Tsukiyama T et al. (2006) Identification and characterization of two novel classes of small RNAs in the mouse germline: retrotransposon‐derived siRNAs in oocytes and germline small RNAs in testes. Genes & Development 20: 1732–1743.

White MJ, Webb GC and Cheney J (1973) Cytogenetics of the parthenogenetic grasshopper Moraba virgo and its bisexual relatives I. A new species of the virgo group with a unique sex chromosome mechanism. Chromosoma 40: 199–212.

Zhang R, Peng Y, Wang W and Su B (2007) Rapid evolution of an X‐linked microRNA cluster in primates. Genome Research 17: 612–617.

Further Reading

Burgoyne PS, Mahadevaiah SK and Turner JMA (2009) The consequences of asynapsis for mammalian meiosis. Nature Reviews. Genetics 10(3): 207–216.

Daish T and Grützner F (2009) Location, location, location! Monotremes provide unique insights into the evolution of sex chromosome silencing in mammals. DNA and Cell Biology 28(2): 91–100. Review.

Holmes RJ and Cohen PE (2007) Small RNAs and RNAi pathways in meiotic prophase I. Chromosome Research 15: 653–665.

Khalil AM and Wahlestedt C (2008) Epigenetic mechanisms of gene regulation during mammalian spermatogenesis. Epigenetics 3(1): 21–28. Review.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Daish, Tasman J, and Grützner, Frank(Feb 2010) Meiotic Sex Chromosome Inactivation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022109]