A frog with three sex chromosomes that co-mingle together in nature: Xenopus tropicalis has a degenerate W and a Y that evolved from a Z chromosome

Autoři: Benjamin L. S. Furman aff001;  Caroline M. S. Cauret aff001;  Martin Knytl aff001;  Xue-Ying Song aff001;  Tharindu Premachandra aff001;  Caleb Ofori-Boateng aff004;  Danielle C. Jordan aff005;  Marko E. Horb aff005;  Ben J. Evans aff001
Působiště autorů: Department of Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada aff001;  Department of Zoology, University of British Columbia, 6270 University Blvd Vancouver, British Columbia, V6T 1Z4 Canada aff002;  Department of Cell Biology, Charles University, 7 Vinicna Street, Prague, 12843, Czech Republic aff003;  CSIR-Forestry Research Institute of Ghana, Kumasi, Ghana aff004;  Eugene Bell Center for Regenerative Biology and Tissue Engineering and National Resource, Marine Biological Laboratory, 7 MBL St, Woods Hole, MA 02543 USA aff005
Vyšlo v časopise: A frog with three sex chromosomes that co-mingle together in nature: Xenopus tropicalis has a degenerate W and a Y that evolved from a Z chromosome. PLoS Genet 16(11): e1009121. doi:10.1371/journal.pgen.1009121
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009121


In many species, sexual differentiation is a vital prelude to reproduction, and disruption of this process can have severe fitness effects, including sterility. It is thus interesting that genetic systems governing sexual differentiation vary among—and even within—species. To understand these systems more, we investigated a rare example of a frog with three sex chromosomes: the Western clawed frog, Xenopus tropicalis. We demonstrate that natural populations from the western and eastern edges of Ghana have a young Y chromosome, and that a male-determining factor on this Y chromosome is in a very similar genomic location as a previously known female-determining factor on the W chromosome. Nucleotide polymorphism of expressed transcripts suggests genetic degeneration on the W chromosome, emergence of a new Y chromosome from an ancestral Z chromosome, and natural co-mingling of the W, Z, and Y chromosomes in the same population. Compared to the rest of the genome, a small sex-associated portion of the sex chromosomes has a 50-fold enrichment of transcripts with male-biased expression during early gonadal differentiation. Additionally, X. tropicalis has sex-differences in the rates and genomic locations of recombination events during gametogenesis that are similar to at least two other Xenopus species, which suggests that sex differences in recombination are genus-wide. These findings are consistent with theoretical expectations associated with recombination suppression on sex chromosomes, demonstrate that several characteristics of old and established sex chromosomes (e.g., nucleotide divergence, sex biased expression) can arise well before sex chromosomes become cytogenetically distinguished, and show how these characteristics can have lingering consequences that are carried forward through sex chromosome turnovers.

Klíčová slova:

Genomics – Ghana – Sex chromosomes – Single nucleotide polymorphisms – X chromosomes – Y chromosomes – W chromosomes – Z chromosomes


1. Bachtrog D, Mank JE, Peichel CL, Kirkpatrick M, Otto SP, Ashman TL, et al. Sex determination: Why so many ways of doing it? PLoS Biology. 2014;12(7):e1001899. doi: 10.1371/journal.pbio.1001899 24983465

2. Lahn BT, Page DC. Four evolutionary strata on the human X chromosome. Science. 1999;286(5441):964–967. doi: 10.1126/science.286.5441.964 10542153

3. Zhou Q, Zhang J, Bachtrog D, An N, Huang Q, Jarvis ED, et al. Complex evolutionary trajectories of sex chromosomes across bird taxa. Science. 2014;346(6215):1246338. doi: 10.1126/science.1246338 25504727

4. Matsubara K, Tarui H, Toriba M, Yamada K, Nishida-Umehara C, Agata K, et al. Evidence for different origin of sex chromosomes in snakes, birds, and mammals and step-wise differentiation of snake sex chromosomes. Proceedings of the National Academy of Sciences. 2006;103(48):18190–18195. doi: 10.1073/pnas.0605274103 17110446

5. Bachtrog D. Y-chromosome evolution: Emerging insights into processes of Y-chromosome degeneration. Nature Reviews Genetics. 2013;14(2):113–124. doi: 10.1038/nrg3366 23329112

6. Wright AE, Dean R, Zimmer F, Mank JE. How to make a sex chromosome. Nature Communications. 2016;7(1):1–8. doi: 10.1038/ncomms12087

7. Deakin J. Chromosome evolution in marsupials. Genes. 2018;9(2):72. doi: 10.3390/genes9020072

8. Kamiya T, Kai W, Tasumi S, Oka A, Matsunaga T, Mizuno N, et al. A trans-species missense SNP in Amhr2 is associated with sex determination in the tiger pufferfish, Takifugu rubripes (fugu). PLoS Genetics. 2012;8(7):e1002798. doi: 10.1371/journal.pgen.1002798 22807687

9. Adolfsson S, Ellegren H. Lack of dosage compensation accompanies the arrested stage of sex chromosome evolution in ostriches. Molecular Biology and Evolution. 2013;30(4):806–810. doi: 10.1093/molbev/mst009 23329687

10. Perrin N. Sex reversal: A fountain of youth for sex chromosomes? Evolution: International Journal of Organic Evolution. 2009;63(12):3043–3049. doi: 10.1111/j.1558-5646.2009.00837.x 19744117

11. Vicoso B, Kaiser VB, Bachtrog D. Sex-biased gene expression at homomorphic sex chromosomes in emus and its implication for sex chromosome evolution. Proceedings of the National Academy of Sciences. 2013;110(16):6453–6458. doi: 10.1073/pnas.1217027110 23547111

12. Bull JJ. Evolution of sex determining mechanisms. The Benjamin/Cummings Publishing Company, Inc.; 1983.

13. Volff JN, Nanda I, Schmid M, Schartl M. Governing sex determination in fish: Regulatory putsches and ephemeral dictators. Sexual Development. 2007;1(2):85–99. doi: 10.1159/000100030 18391519

14. Miura I. An evolutionary witness: The frog Rana rugosa underwent change of heterogametic sex from XY male to ZW female. Sexual Development. 2007;1(6):323–331. doi: 10.1159/000111764 18391544

15. Jeffries DL, Lavanchy G, Sermier R, Sredl MJ, Miura I, Borzée A, et al. A rapid rate of sex-chromosome turnover and non-random transitions in true frogs. Nature Communications. 2018;9(1):4088. doi: 10.1038/s41467-018-06517-2 30291233

16. Saunders PA, Neuenschwander S, Perrin N. Impact of deleterious mutations, sexually antagonistic selection, and mode of recombination suppression on transitions between male and female heterogamety. Heredity. 2019;123(3):419–428. doi: 10.1038/s41437-019-0225-z 31028370

17. Vicoso B. Molecular and evolutionary dynamics of animal sex-chromosome turnover. Nature Ecology and Evolution. 2019; p. 1–10. 31768022

18. Myosho T, Takehana Y, Hamaguchi S, Sakaizumi M. Turnover of sex chromosomes in celebensis group medaka fishes. G3: Genes, Genomes, Genetics. 2015;5(12):2685–2691. doi: 10.1534/g3.115.021543 26497145

19. Tennessen JA, Wei N, Straub SC, Govindarajulu R, Liston A, Ashman TL. Repeated translocation of a gene cassette drives sex-chromosome turnover in strawberries. PLoS Biology. 2018;16(8):e2006062. doi: 10.1371/journal.pbio.2006062 30148831

20. Yano A, Nicol B, Jouanno E, Quillet E, Fostier A, Guyomard R, et al. The sexually dimorphic on the Y-chromosome gene (sdY) is a conserved male-specific Y-chromosome sequence in many salmonids. Evolutionary applications. 2013;6(3):486–496. doi: 10.1111/eva.12032 23745140

21. Blaser O, Grossen C, Neuenschwander S, Perrin N. Sex-chromosome turnovers induced by deleterious mutation load. Evolution: International Journal of Organic Evolution. 2013;67(3):635–645. 23461315

22. Blaser O, Neuenschwander S, Perrin N. Sex-chromosome turnovers: The hot-potato model. The American Naturalist. 2014;183(1):140–146. doi: 10.1086/674026 24334743

23. Evans BJ, Pyron RA, Wiens JJ. Polyploidization and sex chromosome evolution in amphibians. In: Polyploidy and Genome Evolution. Springer; 2012. p. 385–410.

24. Pennell MW, Mank JE, Peichel CL. Transitions in sex determination and sex chromosomes across vertebrate species. Molecular Ecology. 2018;27(19):3950–3963. doi: 10.1111/mec.14540 29451715

25. Cauret CM, Gansauge MT, Tupper AS, Furman BL, Knytl M, Song XY, et al. Developmental systems drift and the drivers of sex chromosome evolution. Molecular Biology and Evolution. 2020;37(3):799–810. doi: 10.1093/molbev/msz268 31710681

26. Green DM, Zeyl CW, Sharbel TF. The evolution of hypervariable sex and supernumerary (B) chromosomes in the relict New Zealand frog, Leiopelma hochstetteri. Journal of Evolutionary Biology. 1993;6(3):417–441. doi: 10.1046/j.1420-9101.1993.6030417.x

27. Roco ÁS, Olmstead AW, Degitz SJ, Amano T, Zimmerman LB, Bullejos M. Coexistence of Y, W, and Z sex chromosomes in Xenopus tropicalis. Proceedings of the National Academy of Sciences. 2015;112(34):E4752–E4761. doi: 10.1073/pnas.1505291112

28. Olmstead AW, Lindberg-Livingston A, Degitz SJ. Genotyping sex in the amphibian, Xenopus (Silurana) tropicalis, for endocrine disruptor bioassays. Aquatic Toxicology. 2010;98(1):60–66. doi: 10.1016/j.aquatox.2010.01.012 20202696

29. Mitros T, Lyons J, Session A, Jenkins J, Shu S, Kwon T, et al. A chromosome-scale genome assembly and dense genetic map for Xenopus tropicalis. Developmental Biology. 2019.

30. Tymowska J. Polyploidy and cytogenetic variation in frogs of the genus Xenopus. Amphibian cytogenetics and evolution. 1991;259:297.

31. Bewick AJ, Chain FJ, Zimmerman LB, Sesay A, Gilchrist MJ, Owens ND, et al. A large pseudoautosomal region on the sex chromosomes of the frog Silurana tropicalis. Genome Biology and Evolution. 2013;5(6):1087–1098. doi: 10.1093/gbe/evt073 23666865

32. Evans BJ, Gansauge MT, Stanley EL, Furman BL, Cauret CM, Ofori-Boateng C, et al. Xenopus fraseri: Mr. Fraser, where did your frog come from? PloS One. 2019;14(9).

33. Grainger RM. Xenopus tropicalis as a model organism for genetics and genomics: Past, present, and future. In: Xenopus Protocols. Springer; 2012. p. 3–15.

34. Blum M, Ott T. Xenopus: an undervalued model organism to study and model human genetic disease. Cells Tissues Organs. 2018;205(5-6):303–313. doi: 10.1159/000490898 30092565

35. Showell C, Conlon FL. The Western clawed frog (Xenopus tropicalis): An emerging vertebrate model for developmental genetics and environmental toxicology. Cold Spring Harbor Protocols. 2009;2009(9):pdb–emo131. doi: 10.1101/pdb.emo131 20147259

36. Yoshimoto S, Okada E, Umemoto H, Tamura K, Uno Y, Nishida-Umehara C, et al. A W-linked DM-domain gene, DM-W, participates in primary ovary development in Xenopus laevis. Proceedings of the National Academy of Sciences. 2008;105(7):2469–2474. doi: 10.1073/pnas.0712244105 18268317

37. Song XY, Furman BL, Premachandra T, Knytl M, Cauret CMS, Wasonga DV, et al. Sex-biased expression of sex-linked transcripts in African clawed frogs (Xenopus). Philosophical Transactions of the Royal Society B;in press.

38. Furman BLS, Evans BJ. Sequential turnovers of sex chromosomes in African clawed frogs (Xenopus) suggest some genomic regions are good at sex determination. G3: Genes|Genomes|Genetics. 2016;6(11):3625–3633. doi: 10.1534/g3.116.033423 27605520

39. Tinsley R, Loumont C, Kobel H. Geographical distribution and ecology. In: Tinsley R, Kobel H, editors. The Biology of Xenopus. Oxford: Clarendon Press; 1996. p. 35–41.

40. Miller CS, Gosling WD. Quaternary forest associations in lowland tropical West Africa. Quaternary Science Reviews. 2014;84:7–25. doi: 10.1016/j.quascirev.2013.10.027

41. Demenou BB, Doucet JL, Hardy OJ. History of the fragmentation of the African rain forest in the Dahomey Gap: Insight from the demographic history of Terminalia superba. Heredity. 2018;120(6):547–561. doi: 10.1038/s41437-017-0035-0 29279603

42. Düsing K. The regulation of the gender ratio in the multiplication of the people, animals and plants. Fischer; 1884.

43. Fisher RA. The genetical theory of natural selection. The Clarendon Press; 1958.

44. Hamilton WD. Extraordinary sex ratios. Science. 1967;156(3774):477–488. doi: 10.1126/science.156.3774.477 6021675

45. Vuilleumier S, Lande R, Van Alphen J, Seehausen O. Invasion and fixation of sex-reversal genes. Journal of Evolutionary Biology. 2007;20(3):913–920. doi: 10.1111/j.1420-9101.2007.01311.x 17465902

46. Bateman A, Anholt B. Maintenance of polygenic sex determination in a fluctuating environment: an individual-based model. Journal of Evolutionary Biology. 2017;30(5):915–925. doi: 10.1111/jeb.13054 28187242

47. Bewick AJ, Anderson DW, Evans BJ. Evolution of the closely related, sex-related genes DM-W and DMRT1 in African clawed frogs (Xenopus). Evolution: International Journal of Organic Evolution. 2011;65(3):698–712. doi: 10.1111/j.1558-5646.2010.01163.x

48. Hellsten U, Harland RM, Gilchrist MJ, Hendrix D, Jurka J, Kapitonov V, et al. The genome of the Western Clawed Frog Xenopus tropicalis. Science. 2010;328(5978):633–636. doi: 10.1126/science.1183670 20431018

49. Chain FJ. Sex-biased expression of young genes in Silurana (Xenopus) tropicalis. Cytogenetic and Genome Research. 2015;145(3-4):265–277. doi: 10.1159/000430942 26065714

50. Kitano J, Kakioka R, Ishikawa A, Toyoda A, Kusakabe M. Differences in the contributions of sex-linkage and androgen regulation to sex-biased gene expression in juvenile and adult sticklebacks. Journal of Evolutionary Biology. 2020;. doi: 10.1111/jeb.13662 32533720

51. Bull JJ, Charnov EL. Changes in the heterogametic mechanism of sex determination. Heredity. 1977;39(1):1. 268319

52. Charlesworth B, Coyne JA, Barton NH. The relative rates of evolution of sex chromosomes and autosomes. The American Naturalist. 1987;130(1):113–146. doi: 10.1086/284701

53. Vicoso B, Charlesworth B. Effective population size and the faster-X effect: an extended model. Evolution: International Journal of Organic Evolution. 2009;63(9):2413–2426. doi: 10.1111/j.1558-5646.2009.00719.x

54. Malcom JW, Kudra RS, Malone JH. The sex chromosomes of frogs: Variability and tolerance offer clues to genome evolution and function. Journal of Genomics. 2014;2:68. doi: 10.7150/jgen.8044 25031658

55. Furman BL, Dang UJ, Evans BJ, Golding GB. Divergent subgenome evolution after allopolyploidization in African clawed frogs (Xenopus). Journal of Evolutionary Biology. 2018;31(12):1945–1958. doi: 10.1111/jeb.13391 30341989

56. Ottolini CS, Newnham LJ, Capalbo A, Natesan SA, Joshi HA, Cimadomo D, et al. Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates. Nature Genetics. 2015;47(7):727. doi: 10.1038/ng.3306 25985139

57. Sardell JM, Cheng C, Dagilis AJ, Ishikawa A, Kitano J, Peichel CL, et al. Sex differences in recombination in sticklebacks. G3: Genes, Genomes, Genetics. 2018;8(6):1971–1983. doi: 10.1534/g3.118.200166 29632132

58. Brelsford A, Dufresnes C, Perrin N. High-density sex-specific linkage maps of a European tree frog (Hyla arborea) identify the sex chromosome without information on offspring sex. Heredity. 2016;116(2):177. doi: 10.1038/hdy.2015.83 26374238

59. Berset-Brändli L, Jaquiéry J, Broquet T, Ulrich Y, Perrin N. Extreme heterochiasmy and nascent sex chromosomes in European tree frogs. Proceedings of the Royal Society B: Biological Sciences. 2008;275(1642):1577–1585. doi: 10.1098/rspb.2008.0298 18426748

60. Theodosiou L, McMillan W, Puebla O. Recombination in the eggs and sperm in a simultaneously hermaphroditic vertebrate. Proceedings of the Royal Society B: Biological Sciences. 2016;283(1844):20161821. doi: 10.1098/rspb.2016.1821 27974520

61. Sutherland BJ, Rico C, Audet C, Bernatchez L. Sex chromosome evolution, heterochiasmy, and physiological QTL in the salmonid brook charr Salvelinus fontinalis. G3: Genes, Genomes, Genetics. 2017;7(8):2749–2762. doi: 10.1534/g3.117.040915 28626004

62. Sardell JM, Kirkpatrick M. Sex differences in the recombination landscape. The American Naturalist. 2020;195(2):361–379. doi: 10.1086/704943 32017625

63. Brandvain Y, Coop G. Scrambling eggs: meiotic drive and the evolution of female recombination rates. Genetics. 2012;190(2):709–723. doi: 10.1534/genetics.111.136721 22143919

64. Charlesworth B, Charlesworth D. The degeneration of Y chromosomes. Philosophical Transactions of the Royal Society of London Series B: Biological Sciences. 2000;355(1403):1563–1572. doi: 10.1098/rstb.2000.0717 11127901

65. Baird NA, Etter PD, Atwood TS, Currey MC, Shiver AL, Lewis ZA, et al. Rapid SNP discovery and genetic mapping using sequenced RAD markers. PLoS One. 2008;3(10):e3376. doi: 10.1371/journal.pone.0003376 18852878

66. Rungger D. Xenopus helveticus, an endangered species? International Journal of Developmental Biology. 2002;46(1):49–63. 11902687

67. Baxter SW, Davey JW, Johnston JS, Shelton AM, Heckel DG, Jiggins CD, et al. Linkage mapping and comparative genomics using next-generation RAD sequencing of a non-model organism. PloS One. 2011;6(4):e19315. doi: 10.1371/journal.pone.0019315 21541297

68. Bolger AM, Lohse M, Usadel B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics. 2014; p. btu170. doi: 10.1093/bioinformatics/btu170 24695404

69. Li H, Durbin R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics. 2009;25(14):1754–1760. doi: 10.1093/bioinformatics/btp324 19451168

70. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The sequence alignment/map format and SAMtools. Bioinformatics. 2009;25(16):2078–2079. doi: 10.1093/bioinformatics/btp352 19505943

71. Li H. A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics. 2011;27(21):2987–2993. doi: 10.1093/bioinformatics/btr509 21903627

72. Andrews KR, Good JM, Miller MR, Luikart G, Hohenlohe PA. Harnessing the power of RADseq for ecological and evolutionary genomics. Nature Reviews Genetics. 2016;17(2):81. doi: 10.1038/nrg.2015.28 26729255

73. Glaubitz JC, Casstevens TM, Lu F, Harriman J, Elshire RJ, Sun Q, et al. TASSEL-GBS: A high capacity genotyping by sequencing analysis pipeline. PloS One. 2014;9(2):e90346. doi: 10.1371/journal.pone.0090346 24587335

74. Goudet J, Raymond M, de Meeüs T, Rousset F. Testing differentiation in diploid populations. Genetics. 1996;144(4):1933–1940. 8978076

75. Skotte L, Korneliussen TS, Albrechtsen A. Estimating individual admixture proportions from next generation sequencing data. Genetics. 2013;195(3):693–702. doi: 10.1534/genetics.113.154138 24026093

76. Jakobsson M, Rosenberg NA. CLUMPP: A cluster matching and permutation program for dealing with label switching and multimodality in analysis of population structure. Bioinformatics. 2007;23(14):1801–1806. doi: 10.1093/bioinformatics/btm233 17485429

77. Bhatia G, Patterson N, Sankararaman S, Price AL. Estimating and interpreting FST: The impact of rare variants. Genome Research. 2013;23(9):1514–1521. doi: 10.1101/gr.154831.113 23861382

78. Nieuwkoop PD. Normal table of Xenopus laevis (Daudin). Normal table of Xenopus laevis (Daudin). 1956; p. 162–203.

79. Bray NL, Pimentel Haroldand Melsted P, Pachter L. Near-optimal probabilistic RNA-seq quantification. Nature Biotechnology. 2016;34(5):525–527. doi: 10.1038/nbt.3519 27043002

80. Robinson MD, McCarthy DJ, Smyth GK. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26(1):139–140. doi: 10.1093/bioinformatics/btp616 19910308

81. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology. 2014;15(12):550. doi: 10.1186/s13059-014-0550-8 25516281

82. Zhu A, Ibrahim JG, Love MI. Heavy-tailed prior distributions for sequence count data: removing the noise and preserving large differences. Bioinformatics. 2019;35(12):2084–2092. doi: 10.1093/bioinformatics/bty895 30395178

83. Wu TD, Watanabe CK. GMAP: A genomic mapping and alignment program for mRNA and EST sequences. Bioinformatics. 2005;21(9):1859–1875. doi: 10.1093/bioinformatics/bti310 15728110

84. Wagner GP, Kin K, Lynch VJ. Measurement of mRNA abundance using RNA-seq data: RPKM measure is inconsistent among samples. Theory in biosciences. 2012;131(4):281–285. doi: 10.1007/s12064-012-0162-3 22872506

85. Signorell A, et al. DescTools: Tools for Descriptive Statistics; 2020. Available from: https://cran.r-project.org/package=DescTools.

86. Margarido GRA, de Souza AP, Garcia AAF. OneMap: Software for genetic mapping in outcrossing species. Hereditas. 2007;144:78–79. doi: 10.1111/j.2007.0018-0661.02000.x 17663699

87. R Core Team. R: A Language and Environment for Statistical Computing; 2016. Available from: https://www.R-project.org/.

88. Karimi K, Fortriede JD, Lotay VS, Burns KA, Wang DZ, Fisher ME, et al. Xenbase: a genomic, epigenomic and transcriptomic model organism database. Nucleic Acids Research. 2018;46(D1):D861–D868. doi: 10.1093/nar/gkx936 29059324

Článek vyšel v časopise

PLOS Genetics

2020 Číslo 11

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Zvyšte si kvalifikaci online z pohodlí domova

Antiseptika a prevence ve stomatologii
nový kurz
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Citikolin v neuroprotekci a neuroregeneraci: od výzkumu do klinické praxe nejen očních lékařů
Autoři: MUDr. Petr Výborný, CSc., FEBO

Zánětlivá bolest zad a axiální spondylartritida – Diagnostika a referenční strategie
Autoři: MUDr. Monika Gregová, Ph.D., MUDr. Kristýna Bubová

Diagnostika a léčba deprese pro ambulantní praxi
Autoři: MUDr. Jan Hubeňák, Ph.D

Význam nemocničního alert systému v době SARS-CoV-2
Autoři: doc. MUDr. Helena Lahoda Brodská, Ph.D., prim. MUDr. Václava Adámková

Všechny kurzy
Kurzy Doporučená témata Časopisy
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se