Mammalian sex chromosomes appear, behave and function differently than the autosomes, passing on their genes in a unique sex-linked manner. The publishing of Ohno’s hypothesis provided a framework for discussion of sex chromosome evolution, allowing it to be developed and challenged numerous times. In this report we discuss the pressures that drove the evolution of sex and the mechanisms by which it occurred. We concentrate on how the sex chromosomes evolved in mammals, discussing the various hypotheses proposed and the evidence supporting them.   

1.
Adler DA, Bressler SL, Chapman VM, Page DC, Disteche CM: Inactivation of the Zfx gene on the mouse X chromosome. Proc natl Acad Sci, USA 88:4592–4595 (1991).
2.
Allen EF, Albrecht I, Drake JW: Properties of bacteriophage T4 mutants defective in DNA polymerase. Genetics 65:187–200 (1970).
3.
Ariel M, Robinson E, McCarrey JR, Cedar H: Gamete-specific methylation correlates with imprinting of the murine Xist gene. Nature Genet 9:312–315 (1995).
4.
Baverstock PR, Adams M, Polkinghorne RW, Gelder M: A sex-linked enzyme in birds – Z-chromosome conservation but no dosage compensation. Nature 296:763–766 (1982).
5.
Bickmore WA, Cooke HJ: Evolution of homologous sequences on the human X and Y chromosomes, outside of the meiotic pairing segment. Nucl Acids Res 15:6261–6271 (1987).
6.
Borsani G, Tonlorenzi R, Simmler MC, Dandolo L, Arnaud D, Capra V, Grompe M, Pizzuti A, Muzny D, Lawrence C: Characterization of a murine gene expressed from the inactive X chromosome. Nature 351:325–329 (1991).
7.
Bowles J, Koopman P: New clues to the puzzle of mammalian sex determination. Genome Biol 2:1025 (2001).
8.
Brockdorff N, Ashworth A, Kay GF, McCabe VM, Norris DP, Cooper PJ, Swift S, Rastan S: The product of the mouse Xist gene is a 15-kb inactive X-specific transcript containing no conserved ORF and located in the nucleus. Cell 71:515–526 (1992).
9.
Brown WR: A physical map of the human pseudoautosomal region. EMBO J 7:2377–2385 (1988).
10.
Brown CJ, Willard HF: The human X-inactivation centre is not required for maintenance of X- chromosome inactivation. Nature 368:154–156 (1994).
11.
Brown CJ, Ballabio A, Rupert JL, Lafreniere RG, Grompe M, Tonlorenzi R, Willard HF: A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349:38–44 (1991).
12.
Brown CJ, Hendrich BD, Rupert JL, Lafreniere RG, Xing Y, Lawrence J, Willard HF: The human XIST gene: analysis of a 17-kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell 71:527–542 (1992).
13.
Bull JJ: Evolution of Sex Determining Mechanisms (Benjamin/Cummings, Don Mills 1983).
14.
Burgoyne PS: Genetic homology and crossing over in the X and Y chromosomes of mammals. Hum Genet 61:85–90 (1982).
15.
del Castillo I, Cohen-Salmon M, Blanchard S, Lutfalla G, Petit C: Structure of the X-linked Kallmann syndrome gene and its homologous pseudogene on the Y chromosome. Nature Genet 2:305–310 (1992).
16.
Chan WY, Rennert OM: Molecular aspects of sex differentiation. Current molec Med 2:25–37 (2002).
17.
Charlesworth B: Model for evolution of Y chromosomes and dosage compensation. Proc natl Acad Sci, USA 75:5618–5622 (1978).
18.
Charlesworth B: The evolution of sex chromosomes. Science 251:1030–1033 (1991).
19.
Charlesworth B: The evolution of chromosomal sex determination and dosage compensation. Current Biol 6:149–162 (1996).
20.
Charlesworth B, Charlesworth D: The degeneration of Y chromosomes. Phil Trans R Soc London – Series B: Biol Sci 355:1563–1572 (2000).
21.
Christidis L: Chromosomal repatterning and systemics in the passeriformes (songbirds). Chrom Today 10:279–294 (1989).
22.
Clark MS, Wall WJ: Chromosomes, the Complex Code (Chapman and Hall, London 1996).
23.
Cooke HJ, Brown WR, Rappold GA: Hypervariable telomeric sequences from the human sex chromosomes are pseudoautosomal. Nature 317:687–692 (1985).
24.
Crow JF: Advantages of sexual reproduction. Dev Genet 15:205–213 (1994).
25.
Dominguez-Steglich M, Meng G, Bettecken T, Muller CR, Schmid M: The dystrophin gene is autosomally located on a microchromosome in chicken. Genomics 8:536–540 (1990).
26.
Dorit RL, Akashi H, Gilbert W: Absence of polymorphism at the ZFY locus on the human Y chromosome. Science 268:1183–1185 (1995).
27.
Ellis NA: Human Genome Evolution, in Strachan T, Read A (eds): Human Molecular Genetics, Chapter 10 (John Wiley and Sons, New York 1996).
28.
Ellis NA, Goodfellow PJ, Pym B, Smith M, Palmer M, Frischauf AM, Goodfellow PN: The pseudoautosomal boundary in man is defined by an Alu repeat sequence inserted on the Y chromosome. Nature 337:81–84 (1989).
29.
Ellis N, Yen P, Neiswanger K, Shapiro LJ, Goodfellow PN: Evolution of the pseudoautosomal boundary in Old World monkeys and great apes. Cell 63:977–986 (1990).
30.
Felsenstein J: The evolutionary advantage of recombination. Genetics 78:737–756 (1974).
31.
Forwood JK, Harley V, Jans DA: The C-terminal nuclear localization signal of the sex-determining region Y (SRY) high mobility group domain mediates nuclear import through importin beta 1. J biol Chem 276:46575–46582 (2001).
32.
Fredga K: Aberrant chromosomal sex-determining mechanisms in mammals, with special reference to species with XY females. Phil Trans R Soc London – Series B: Biol Sci 322:83–95 (1988).
33.
Freije D, Helms C, Watson MS, Donis-Keller H: Identification of a second pseudoautosomal region near the Xq and Yq telomeres. Science 258:1784–1787 (1992).
34.
Gabriel-Robez O, Rumpler Y, Ratomponirina C, Petit C, Levilliers J, Croquette MF, Couturier J: Deletion of the pseudoautosomal region and lack of sex-chromosome pairing at pachytene in two infertile men carrying an X;Y translocation. Cytogenet Cell Genet 54:38–42 (1990).
35.
Gartler SM, Dyer KA, Goldman MA: Mammalian X chromosome inactivation. Mol Genet Med 2:121–160 (1992).
36.
Gerhart J, Kirschner M: Cells, Embryos and Evolution: Toward a Cellular and Developmental Understanding of Phenotypic Variation and Evolutionary Adaptability (Blackwell Science, Malden 1997).
37.
Glas R, Marshall Graves JA, Toder R, Ferguson-Smith M, O’Brien PC: Cross-species chromosome painting between human and marsupial directly demonstrates the ancient region of the mammalian X. Mammal Genome 10:1115–1116 (1999).
38.
Graves JA: The origin and function of the mammalian Y chromosome and Y-borne genes – an evolving understanding. Bioessays 17:311–320 (1995).
39.
Graves JA: Evolution of the mammalian Y chromosome and sex-determining genes. J Exp Zool 281:472–481 (1998).
40.
Graves JA: Human Y chromosome, sex determination, and spermatogenesis – a feminist view. Article. Biol Reprod 63:667–676 (2000).
41.
Graves JA, Disteche CM, Toder R: Gene dosage in the evolution and function of mammalian sex chromosomes. Cytogenet Cell Genet 80:94–103 (1998a).
42.
Graves JA, Wakefield MJ, Toder R: The origin and evolution of the pseudoautosomal regions of human sex chromosomes. Hum molec Genet 7:1991–1996 (1998b).
43.
Griffin DK, Harvey SC, Campos-Ramos R, Ayling L-J, Bromage NR, Masabanda JS, Penman D: Early origins of the X and Y chromosome: lessons from tilapia. Cytogenet Genome Res 99:157–163 (2003).
44.
Grumbach MM, Morishima A, Taylor JH: Human sex chromosome abnormalities in relation to DNA replication and heterochromatinization. Proc natl Acad Sci, USA 49:581–589 (1963).
45.
Hammer MF: A recent common ancestry for human Y chromosomes. Nature 378:376–378 (1995).
46.
Hartshorn C. Rice JE. Wangh LJ: Developmentally-regulated changes of Xist RNA levels in simple preimplantation mouse embryos, as revealed by quantitative real-time PCR. Mol Reprod Dev 61:425–436 (2002).
47.
Hassold TJ, Sherman SL, Pettay D, Page DC, Jacobs PA: XY chromosome nondisjunction in man is associated with diminished recombination in the pseudoautosomal region. Am J hum Genet 49:253–260 (1991).
48.
Hope RM, Cooper S, Wainwright B: Globin Macromolecular Sequences in Marsupials and Monotremes, Mammals from Pouches and Eggs: Genetics, Breeding and Evolution of Marsupials and Monotremes. (CSIRO Press, Melborne 1990).
49.
Hurst LD, Peck JR: Recent advances in understanding the evolution and maintenance of sex. Trends Ecol Evol 11:46–52 (1996).
50.
Incerti B, Guioli S, Pragliola A, Zanaria E, Borsani G, Tonlorenzi R, Bardoni B, Franco B, Wheeler D, Ballabio A: Kallmann syndrome gene on the X and Y chromosomes: implications for evolutionary divergence of human sex chromosomes. Nature Genet 2:311–314 (1992).
51.
Jegalian K, Lahn BT: Why the Y. Sci Am 284(2):42–47 (2001).
52.
Jones S: The Language of the Genes: Biology, History and Evolutionary Future (HarperCollins, London 1994).
53.
Jost A, Vigier B, Prepin J, Perchellet JP: Studies on sex differentiation in mammals. Recent Prog Horm Res 29:1–41 (1973).
54.
Just W, Rau W, Vogel W, Akhverdian M, Fredga K, Graves JA, Lyapunova E: Absence of Sry in species of the vole Ellobius. Nature Genet 11:117–118 (1995).
55.
Karpen GH, Le MH, Le H: Centric heterochromatin and the efficiency of achiasmate disjunction in Drosophila female meiosis. Science 273:118–122 (1996).
56.
Kay GF, Penny GD, Patel D, Ashworth A, Brockdorff N, Rastan S: Expression of Xist during mouse development suggests a role in the initiation of X chromosome inactivation. Cell 72:171–182 (1993).
57.
Kay GF, Barton SC, Surani MA, Rastan S: Imprinting and X chromosome counting mechanisms determine Xist expression in early mouse development. Cell 77:639–650 (1994).
58.
Kipling D, Salido EC, Shapiro LJ, Cooke HJ: High frequency de novo alterations in the long-range genomic structure of the mouse pseudoautosomal region. Nature Genet 13:78–80 (1996).
59.
Koopman P, Munsterberg A, Capel B, Vivian N, Lovell-Badge R: Expression of a candidate sex-determining gene during mouse testis differentiation. Nature 348:450–452 (1990).
60.
Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R: Male development of chromosomally female mice transgenic for Sry. Nature 351:117–121 (1991).
61.
Kvaloy K, Galvagni F, Brown WR: The sequence organization of the long arm pseudoautosomal region of the human sex chromosomes. Hum molec Genet 3:771–778 (1994).
62.
Lee C, Griffin DK, O’Brien PC, Yang F, Lin CC, Ferguson-Smith MA: Defining the anatomy of the Rangifer tarandus sex chromosomes. Chromosoma 107:61–69 (1998).
63.
Lee JT, Davidow LS, Warshawsky D: Tsix, a gene antisense to Xist at the X-inactivation center. Nature Genet 21:400–404 (1999).
64.
Li B, Zhang W, Chan G, Jancso-Radek A, Liu S, Weiss MA: Human sex reversal due to impaired nuclear localization of SRY: A clinical correlation. J biol Chem 276:46480–46484 (2001).
65.
Lifschytz E, Lindsley DL: The role of X-chromosome inactivation during spermatogenesis (Drosophila-allocycly-chromosome evolution-male sterility-dosage compensation). Proc natl Aca Sci, USA 69:182–186 (1972).
66.
McCarrey JR, Dilworth DD: Expression of Xist in mouse germ cells correlates with X-chromosome inactivation. Nature Genet 2:200–203 (1992).
67.
McKay LM, Watson JM, Graves JA: Mapping human X-linked genes in the phalangerid marsupial Trichosurus vulpecula. Genomics 14:302–308 (1992).
68.
Migeon BR: X-chromosome inactivation: molecular mechanisms and genetic consequences. Trends Genet 10:230–235 (1994).
69.
Mohandas TK, Speed RM, Passage MB, Yen PH, Chandley AC, Shapiro LJ: Role of the pseudoautosomal region in sex-chromosome pairing during male meiosis: meiotic studies in a man with a deletion of distal Xp. Am J hum Genet 51:526–533 (1992).
70.
Muller HJ: The relation of recombination to mutational advance. Mutat Res 1:2–9 (1964).
71.
Murphy EC, Zhurkin VB, Louis JM, Cornilescu G, Clore GM: Structural basis for SRY-dependent 46-X,Y sex reversal: modulation of DNA bending by a naturally occurring point mutation. J molec Biol 312:481–499 (2001).
72.
Ohno S: Sex Chromosomes and Sex Linked Genes. (Springer, New York 1967).
73.
Ortenberg J, Oddoux C, Craver R, McElreavey K, Salas-Cortes L, Guillen-Navarro E, Ostrer H, Sarafoglou K: SRY gene expression in the ovotestes of XX true hermaphrodites. J Urol 167:1828–1831 (2002).
74.
Ottolenghi C, Fellous M, Barbieri M, McElreavey K: Novel paralogy relations among human chromosomes support a link between the phylogeny of doublesex-related genes and the evolution of sex determination. Genomics 79:333–343 (2002).
75.
Page DC, Mosher R, Simpson EM, Fisher EM, Mardon G, Pollack J, McGillivray B, de la Chapelle A, Brown LG: The sex-determining region of the human Y chromosome encodes a finger protein. Cell 51:1091–1104 (1987).
76.
Page J, Berrios S, Rufas JS, Parra MT, Suja JA, Heyting C, Fernandez-Donoso R: 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. J Cell Sci 116:551–560 (2003).
77.
Pailhoux E, Parma P, Sundstrom J, Vigier B, Servel N, Kuopio T, Locatelli A, Pelliniemi LJ, Cotinot C: Time course of female-to-male sex reversal in 38,XX fetal and postnatal pigs. Dev Dynam 222:328–340 (2001).
78.
Palmer MS, Berta P, Sinclair AH, Pym B, Goodfellow PN: Comparison of human ZFY and ZFX transcripts. Proc natl Acad Sci, USA 87:1681–1685 (1990).
79.
Petit C, Levilliers J, Weissenbach J: Physical mapping of the human pseudo-autosomal region; comparison with genetic linkage map. EMBO J 7:2369–2376 (1988).
80.
Penny GD, Kay GF, Sheardown SA, Rastan S, Brockdorff N: Requirement for Xist in X chromosome inactivation. Nature 379:131–137 (1996).
81.
Quilter C, Sargent C, Archibald A, Affara A, Griffin DK: Mapping of Y specific and X/Y homologous genes in the pig: Implications for sex chromosome evolution. Mammal Genome 13:588–594 (2002).
82.
Rappold GA: The pseudoautosomal regions of the human sex chromosomes. Hum Genet 92:315–324 (1993).
83.
Rappold GA, Lehrach H: A long range restriction map of the pseudoautosomal region by partial digest PFGE analysis from the telomere. Nucl Acids Res 16:5361–5377 (1988).
84.
Rastan S: X chromosome inactivation and the Xist gene. Curr Opin Genet Dev 4:292–297 (1994).
85.
Rice WR: Degeneration of a nonrecombining chromosome. Science 263:230–232 (1994).
86.
Richler C, Soreq H, Wahrman J: X inactivation in mammalian testis is correlated with inactive X-specific transcription. Nature Genet 2:192–195 (1992).
87.
Salido EC, Yen PH, Mohandas TK, Shapiro LJ: Expression of the X-inactivation-associated gene XIST during spermatogenesis. Nature Genet 2:196–199 (1992).
88.
Salido EC, Li XM, Yen PH, Martin N, Mohandas TK, Shapiro LJ: Cloning and expression of the mouse pseudoautosomal steroid sulphatase gene (Sts). Nature Genet 13:83–86 (1996).
89.
Schneider-Gadicke A, Beer-Romero P, Brown LG, Nussbaum R, Page DC: ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation. Cell 57:1247–1258 (1989).
90.
Schmid M, Nanda I, Steinlein C, Epplen JT: Evolution of the sex chromosome in amphibia. Chrom Today 10:199–222 (1989).
91.
Sharp P: Sex chromosome pairing during male meiosis in marsupials. Chromosoma 86:27–47 (1982).
92.
Simmler MC, Rouyer F, Vergnaud G, Nystrom-Lahti M, Ngo KY, de la Chapelle A, Weissenbach J: Pseudoautosomal DNA sequences in the pairing region of the human sex chromosomes. Nature 317:692–697 (1985).
93.
Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, Foster JW, Frischauf AM, Lovell-Badge R, Goodfellow PN: A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346:240–244 (1990).
94.
Singh L, Jones KW: Sex reversal in the mouse (Mus musculus) is caused by a recurrent nonreciprocal crossover involving the X and an aberrant Y chromosome. Cell 28:205–216 (1982).
95.
Sola L, Cataudella S, Capanna E: New developments in vertebrate cytotaxonomy. III. Karyology of bony fishes: a review. Genetica 54:285–328 (1981).
96.
Spencer JA, Sinclair AH, Watson JM, Graves JA: Genes on the short arm of the human X chromosome are not shared with the marsupial X. Genomics 11:339–345 (1991a).
97.
Spencer JA, Watson JM, Graves JA: The X chromosome of marsupials shares a highly conserved region with eutherians. Genomics 9:598–604 (1991b).
98.
Switonski M, Jackowiak H, Godynicki S, Klukowska J, Borsiak K, Urbaniak K: Familial occurrence of pig intersexes (38,XX; SRY-negative) on a commercial fattening farm. Anim Reprod Sci 69:117–124 (2002).
99.
Takagi N, Sasaki M: Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse. Nature 256:640–642 (1975).
100.
Toder R, Wakefield MJ, Graves JA: The minimal mammalian Y chromosome – the marsupial Y as a model system Cytogenet Cell Genet 91:285–292 (2000).
101.
Torres-Maldonado L, Moreno-Mendoza N, Landa A, Merchant-Larios H: Timing of SOX9 downregulation and female sex determination in gonads of the sea turtle Lepidochelys olivacea. J Exp Zool 290:498–503 (2001).
102.
Watson JM, Spencer JA, Riggs AD, Graves JA: The X chromosome of monotremes shares a highly conserved region with the eutherian and marsupial X chromosomes despite the absence of X chromosome inactivation. Proc natl Aca Sci, USA 87:7125–7129 (1990).
103.
Watson JM, Spencer JA, Riggs AD, Graves JA: Sex chromosome evolution: platypus gene mapping suggests that part of the human X chromosome was originally autosomal. Proc natl Aca Sci, USA 88:11256–11260 (1991).
104.
Western PS, Harry JL, Graves JA, Sinclair AH: Temperature-dependent sex determination: upregulation of SOX9 expression after commitment to male development. Dev Dynam 214:171–177 (1999a).
105.
Western PS, Harry JL, Graves JA, Sinclair AH: Temperature-dependent sex determination in the American alligator: AMH precedes SOX9 expression. Dev Dynam 216:411–419 (1999b).
106.
Whitfield LS, Sulston JE, Goodfellow PN: Sequence variation of the human Y chromosome. Nature 378:379–380 (1995).
107.
Willard HF, Carrel L: Making sense (and antisense) of the X inactivation center. Proc natl Aca Sci, USA 98:10025–10007 (2001).
108.
Winter PC, Hickey GI, Fletcher HL: Instat Notes in Genetics. (Bios Scientific Publishers, Oxford 1998).
109.
Wrigley JM, Graves JA: Sex chromosome homology and incomplete, tissue-specific X-inactivation suggest that monotremes represent an intermediate stage of mammalian sex chromosome evolution. J Hered 79:115–118 (1988).
110.
Yen PH, Allen E, Marsh B, Mohandas T, Wang N, Taggart RT, Shapiro LJ: Cloning and expression of steroid sulfatase cDNA and the frequent occurrence of deletions in STS deficiency: implications for X-Y interchange. Cell 49:443–454 (1987).
111.
Yen PH, Marsh B, Allen E, Tsai SP, Ellison J, Connolly L, Neiswanger K, Shapiro LJ: The human X-linked steroid sulfatase gene and a Y-encoded pseudogene: evidence for an inversion of the Y chromosome during primate evolution. Cell 55:1123–1135 (1988).
112.
Yuan X, Lu ML, Li T, Balk SP: SRY interacts with and negatively regulates androgen receptor transcriptional activity. J biol Chem 276:46647–46654 (2001).
113.
Zuccotti M, Monk M: Methylation of the mouse Xist gene in sperm and eggs correlates with imprinted Xist expression and paternal X-inactivation. Nature Genet 9:316–320 (1995).
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.