The mole vole Ellobius lutescens is an interesting animal, not only concerning its sex determination mechanism without the Y-chromosomal Sry gene, that triggers sex determination in nearly all other mammalian species, but also regarding the karyotype with an odd number of chromosomes, being identical in male and female animals. The odd chromosome represents the X chromosome, and therefore, even males do not have a Y chromosome. We present an overview of a search for candidate genes of male sex determination in the mole vole Ellobius lutescens. A singular X raises questions about the need for X chromosome inactivation in female cells. We present preliminary data that support a hypothesis that the E. lutescensXist gene may be degenerated and thus non-functional.

Keywords:
Comparative genomics, Evolution, Sex determination, X inactivation
1.
Achermann JC, Ito M, Ito M, Hindmarsh PC, Jameson JL: A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. Nat Genet 22:125–126 (1999).
2.
Achermann JC, Meeks JJ, Larry JJ: Phenotypic spectrum of mutations in DAX-1 and SF-1. Mol Cell Endocrinol 185:17–25 (2001).
3.
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ: Basic local alignment search tool. J Mol Biol 215:403–410 (1990).
4.
Arakawa Y, Nishida-Umehara C, Matsuda Y, Sutou S, Suzuki H: X-chromosomal localization of mammalian Y-linked genes in two XO species of the Ryukyu spiny rat. Cytogenet Genome Res 99:303–309 (2002).
5.
Asdell SA: The genetic sex of intersexual goats and a probable linkage with the gene for hornlessness. Science 99:124 (1944).
6.
Bachtrog D: Adaptation shapes patterns of genome evolution on sexual and asexual chromosomes in Drosophila. Nat Genet 34:215–219 (2003).
7.
Bardoni B, Zanaria E, Guioli S, Floridia G, Worley KC, et al: A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal. Nat Genet 7:497–501 (1994).
8.
Baumstark A, Akhverdyan M, Schulze A, Reisert I, Vogel W, Just W: Exclusion of SOX9 as the testis determining factor in Ellobius lutescens: Evidence for another testis determining gene besides SRY and SOX9. Mol Genet Metab 72:61–66 (2001).
9.
Baumstark A, Hameister H, Hakhverdyan M, Bakloushinskaya I, Just W: Characterization of Pisrt1/Foxl2 in Ellobius lutescens and exclusion as sex-determining genes. Mamm Genome 16:281–289 (2005).
10.
Bishop CE, Whitworth DJ, Qin Y, Agoulnik AI, Agoulnik IU, et al: A transgenic insertion upstream of Sox9 is associated with dominant XX sex reversal in the mouse. Nat Genet 26:490–494 (2000).
11.
Borissov YM, Lyapunova EA, Vorontsov NN: Karyotype evolution in the genus Ellobius (Microtinae, Rodentia). Genetika 27:523–532 (1991).
12.
Boumil RM, Ogawa Y, Sun BK, Huynh KD, Lee JT: Differential methylation of Xite and CTCF sites in Tsix mirrors the pattern of X-inactivation choice in mice. Mol Cell Biol 26:2109–2117 (2006).
13.
Brown CJ, Ballabio A, Rupert JL, Lafrenière RG, Grompe M, et al: A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349:38–44 (1991).
14.
Castro-Sierra E, Wolf U: Replication patterns of the unpaired chromosome No. 9 of the rodent Ellobius lutescens TH. Cytogenetics 6:268–275 (1967).
15.
Chandra HS: Another way of looking at the enigma of sex determination in Ellobius lutescens. Curr Sci 76:1072 (1999).
16.
Chao W, Huynh KD, Spencer RJ, Davidow LS, Lee JT: CTCF, a candidate trans-acting factor for X-inactivation choice. Science 295:345–347 (2002).
17.
Coskun Y: On distribution, morphology and biology of the mole vole, Ellobius lutescens Thomas, 1897 (Mammalia: Rodentia) in eastern Turkey. Zool Middle East 23:5–12 (2001).
18.
de la Chapelle A, Hortling H, Niemi M, Wennstroem J: XX sex chromosomes in a human male. First case. Acta Med Scand 175:Suppl 8 (1964).
19.
De La Maza LM, Sawyer JR: The G and Q banding pattern of Ellobius lutescens. A unique case of sex determination in mammals. Can J Genet Cytol 18:497–502 (1976).
20.
Delbridge ML, Graves JA: Mammalian Y chromosome evolution and the male-specific functions of Y chromosome-borne genes. Rev Reprod 4:101–109 (1999).
21.
Disteche CM, Filippova GN, Tsuchiya KD: Escape from X inactivation. Cytogenet Genome Res 99:36–43 (2002).
22.
Djalali M, Hameister H, Vogel W: Further chromosomal studies on Ellobius lutescens: Heteromorphism of chromosome No.1 is not associated with sex determination. Experientia 42:1281–1282 (1986).
23.
Ferguson-Smith M: The evolution of sex chromosomes and sex determination in vertebrates and the key role of DMRT1. Sex Dev 1:2–11 (2007).
24.
Ford CE, Jones KW, Polani PE, De Almeida JCC, Briggs JH: A sex-chromosome anomaly in a case of gonadal dysgenesis (Turner’s Syndrome). Lancet i:711–713 (1959).
25.
Foster JW, Marshall Graves JA: An SRY-related sequence on the marsupial X chromosome: Implications for the evolution of the mammalian testis-determining gene. Proc Natl Acad Sci USA 91:1927–1931 (1994).
26.
Foster JW, Dominguez-Steglich MA, Guioli S, Kwok C, Weller PA, et al: Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature 372:525–530 (1994).
27.
Ginatulin AA, Ginatulina LK, Borissov YM, Lyapunova EA, Vorontsov NN: Relationship between the study of DNA reassociation kinetics of various chromosomal forms of Ellobius and questions concerning the pathways of chromosome rearrangement during evolution. Mol Biol (Mosk) 11:883–890 (1977).
28.
Graves JA: Evolution of the mammalian Y chromosome and sex-determining genes. J Exp Zool 281:472–481 (1998a).
29.
Graves JA: Interactions between SRY and SOX genes in mammalian sex determination. BioEssays 20:264–269 (1998b).
30.
Graves JA: The rise and fall of SRY. Trends Genet 18:259–264 (2002).
31.
Graves JA: The degenerate Y chromosome – can conversion save it? Reprod Fertil Dev 16:527–534 (2004).
32.
Grutzner F, Rens W, Tsend-Ayush E, El Mogharbel N, O’Brien PC, et al: In the platypus a meiotic chain of ten sex chromosomes shares genes with the bird Z and mammal X chromosomes. Nature 432:913–917 (2004).
33.
Hanley NA, Ball SG, Clement-Jones M, Hagan DM, Strachan T, et al: Expression of steroidogenic factor 1 and Wilms’ tumour 1 during early human gonadal development and sex determination. Mech Dev 87:175–180 (1999).
34.
Hanley NA, Hagan DM, Clement-Jones M, Ball SG, Strachan T, et al: SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development. Mech Dev 91:403–407 (2000).
35.
Honda T, Suzuki H, Itoh M: An unusual sex chromosome constitution found in the amami spinous country-rat, Tokudaia osimensis osimensis. Jap J Genet 52/3:247–249 (1977).
36.
Huang B, Wang S, Ning Y, Lamb AN, Bartley J: Autosomal XX sex reversal caused by duplication of SOX9. Am J Med Genet 87:349–353 (1999).
37.
Hughes JF, Skaletsky H, Pyntikova T, Minx PJ, Graves T, et al: Conservation of Y-linked genes during human evolution revealed by comparative sequencing in chimpanzee. Nature 437:100–103 (2005).
38.
Ion A, Telvi L, Chaussain JL, Galacteros F, Valayer J, et al: A novel mutation in the putative DNA helicase XH2 is responsible for male-to-female sex reversal associated with an atypical form of the ATR-X syndrome. Am J Hum Genet 58:1185–1191 (1996).
39.
Just W, De Almeida JCC, Goldshmidt B, Vogel W: The male pseudohermaphrodite XX polled goat is Zfy and Sry negative. Hereditas 120:71–75 (1994).
40.
Just W, Rau W, Vogel W, Akhverdian M, Fredga K, et al: Absence of Sry in species of the vole Ellobius. Nat Genet 11:117–118 (1995).
41.
Just W, Baumstark A, Hameister H, Schreiner B, Reisert I, et al: The sex determination in Ellobius lutescens remains bizarre. Cytogenet Genome Res 96:146–153 (2002).
42.
Kent WJ: BLAT–the BLAST-like alignment tool. Genome Res 12:656–664 (2002).
43.
Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, et al: The human genome browser at UCSC. Genome Res 12:996–1006 (2002).
44.
Kolomiets OL, Vorontsov NN, Lyapunova EA, Mazurova TF: Ultrastructure, meiotic behavior, and evolution of sex chromosomes of the genus Ellobius. Genetica 84:179–189 (1991).
45.
Lee JT, Davidow LS, Warshawsky D: Tsix, a gene antisense to Xist at the X-inactivation centre. Nat Genet 21:400–404 (1999).
46.
Lyapunova EA, Vorontsov NN, Zakarjan GG: Zygotic mortality in Ellobius lutescens (Rodentia: Microtinae). Experientia 31:417–418 (1975).
47.
Mashal RD, Koontz J, Sklar J: Detection of mutations by cleavage of DNA heteroduplexes with bacteriophage resolvases. Nat Genet 9:177–183 (1995).
48.
Matthey R: La formule chromosomique et le problème de la détermination sexuelle chez Ellobius lutescens Thomas (Rodentia-Muridae-Microtinae). Arch Klaus-Stift Vererb-Forsch 28:65–73 (1953).
49.
Matthey R: Un nouveau type de determination chromosomique du sexe chez les mammiferes Ellobius lutescens Th. et Microtus (Chilotus) oregoni Bachm. (Murides-Microtines). Experientia 14:240–241 (1958).
50.
Matthey R: Etudes sur les chromosomes d’Ellobius lutescens (Mammalia – Muridae – Microtinae). II. Informations complémentaires sur les divisions méiotiques. Rev Suisse Zool 71:401–410 (1964).
51.
McCarrey JR, Watson C, Atencio J, Ostermeier GC, Marahrens Y, et al: X-chromosome inactivation during spermatogenesis is regulated by an Xist/Tsix-independent mechanism in the mouse. Genesis 34:257–266 (2002).
52.
McElreavey K, Salas-Cortes L: X-Y translocations and sex differentiation. Semin Reprod Med 19:133–139 (2001).
53.
Meyers-Wallen VN, Schlafer D, Barr I, Lovell-Badge R, Keyzner A: Sry-negative XX sex reversal in purebred dogs. Mol Reprod Dev 53:266–273 (1999).
54.
Navarro P, Pichard S, Ciaudo C, Avner P, Rougeulle C: Tsix transcription across the Xist gene alters chromatin conformation without affecting Xist transcription: implications for X-chromosome inactivation. Genes Dev 19:1474–1484 (2005).
55.
Nesterova TB, Slobodyanyuk SY, Elisaphenko EA, Shevchenko AI, Johnston C, et al: Characterization of the genomic Xist locus in rodents reveals conservation of overall gene structure and tandem repeats but rapid evolution of unique sequence. Genome Res 11:833–849 (2001).
56.
Ohno S: Conservation of the original X and homology of the X-linked genes in placental mammals, in Labhart A, Mann T, Samuels LT, Zander J (eds): Sex Chromosomes and Sex-Linked Genes, pp 46–72 (Springer, Berlin 1967).
57.
Pailhoux E, Popescu PC, Parma P, Boscher J, Legault C, et al: Genetic analysis of 38XX males with genital ambiguities and true hermaphrodites in pigs. Anim Genet 25:299–305 (1994a).
58.
Pailhoux E, Cribiu EP, Chaffaux S, Darre R, Fellous M, Cotinot C: Molecular analysis of 60,XX pseudohermaphrodite polled goats for the presence of SRY and ZFY genes. J Reprod Fert 100:491–496 (1994b).
59.
Pailhoux E, Vigier B, Chaffaux S, Servel N, Taourit S, et al: A 11.7-kb deletion triggers intersexuality and polledness in goats. Nat Genet 29:453–458 (2001).
60.
Pask AJ, Harry JL, Renfree MB, Marshall Graves JA: Absence of SOX3 in the developing marsupial gonad is not consistent with a conserved role in mammalian sex determination. Genesis 27:145–152 (2000).
61.
Phelan JK, McCabe ER: Mutations in NR0B1(DAX1) and NR5A1 (SF1) responsible for adrenal hypoplasia congenita. Hum Mutat 18:472–487 (2001).
62.
Raymond CS, Parker ED, Kettlewell JR, Brown LG, Page DC, et al: A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators. Hum Mol Genet 8:989–996 (1999).
63.
Raymond CS, Murphy MW, O’Sullivan MG, Bardwell VJ, Zarkower D: Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation. Genes Dev 14:2587–2595 (2000).
64.
Rens W, Grutzner F, O’Brien PC, Fairclough H, Graves JA, Ferguson-Smith MA: Resolution and evolution of the duck-billed platypus karyotype with an X1Y1X2Y2X3Y3X4Y4X5Y5 male sex chromosome constitution. Proc Natl Acad Sci USA 101:16257–16261 (2004).
65.
Rice WR: Genetic hitchhiking and the evolution of reduced genetic activity of the Y sex chromosome. Genetics 116:161–167 (1987).
66.
Rice WR: Degeneration of a nonrecombining chromosome. Science 263:230–232 (1994).
67.
Rozen S, Skaletsky H, Marszalek JD, Minx PJ, Cordum HS, et al: Abundant gene conversion between arms of palindromes in human and ape Y chromosomes. Nature 423:873–876 (2003).
68.
Schimenti J: Synapsis or silence. Nat Genet 37:11–13 (2005).
69.
Selden JR, Moorhead PS, Koo GC, Wachtel SS, Haskins ME, Patterson DF: Inherited XX sex reversal in the cocker spaniel dog. Hum Genet 67:62–69 (1984).
70.
Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, et al: A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346:240–244 (1990).
71.
Sitnikova NA, Romanenko SA, O’Brien PC, Perelman PL, Fu B, et al: Chromosomal evolution of Arvicolinae (Cricetidae, Rodentia). I. The genome homology of tundra vole, field vole, mouse and golden hamster revealed by comparative chromosome painting. Chromosome Res 15:447–456 (2007).
72.
Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L, et al: The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 423:825–837 (2003).
73.
Soullier S, Hanni C, Catzeflis F, Berta P, Laudet V: Male sex determination in the spiny rat Tokudaia osimensis (Rodentia: Muridae) is not Sry dependent. Mamm Genome 9:590–592 (1998).
74.
Stefan Y: Morphologie et structure histologique du système génital mâle d’un rongeur d’Iran: Ellobius lutescens (Thomas). Arch Anat Histol Embryol 50:151–168 (1967a).
75.
Stefan Y: Hypogénitalisme chez un Rongeur d’Iran: Ellobius lutescens Th.: Action comparée d’injections d’hypophyses de rat et d’ellobius sur le système génital de ratons immature. C R Acad Sci Hebd Seances Acad Sci D 264:2487–2489 (1967b).
76.
Stefan Y, Steimer T: The Leydig cell of a hypogonadic rodent (Ellobius lutescens, Th.): correlation between ultrastructure and biosynthetic activity. Biol Reprod 19:913–921 (1978).
77.
Swain A, Narvaez V, Burgoyne PS, Camerino G, Lovell-Badge R: Dax1 antagonizes Sry action in mammalian sex determination. Nature 391:761–767 (1998).
78.
Turner JM: Meiotic sex chromosome inactivation. Development 134:1823–1831 (2007).
79.
Turner JM, Mahadevaiah SK, Elliott DJ, Garchon HJ, Pehrson JR, et al: Meiotic sex chromosome inactivation in male mice with targeted disruptions of Xist. J Cell Sci 115:4097–4105 (2002).
80.
Vaiman D, Schibler L, Oustry-Vaiman A, Pailhoux E, Goldammer T, et al: High-resolution human/goat comparative map of the goat polled/intersex syndrome (PIS): the human homologue is contained in a human YAC from HSA3q23. Genomics 56:31–39 (1999).
81.
Vogel W, Steinbach P, Djalali M, Mehnert K, Ali S, Epplen JT: Chromosome 9 of Ellobius lutescens is the X chromosome. Chromosoma 96:112–118 (1988).
82.
Wagner T, Wirth J, Meyer J, Zabel B, Held M, et al: Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell 79:1111–1120 (1994).
83.
Wolf M, Schempp W, Vogel W: Ellobius lutescens Th. (Rodentia, Microtinae): Q-, R-, and replication banding patterns. Chromosome 1 polymorphism in the male and presumptive heterogamety in the female. Cytogenet Cell Genet 23:117–123 (1979).
© 2007 S. Karger AG, Basel
2007
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.