Most vertebrates develop distinct females and males, where sex is determined by repeatedly evolved environmental or genetic triggers. Undifferentiated sex chromosomes and large genomes have caused major knowledge gaps in amphibians. Only a single master sex-determining gene, the dmrt1-paralogue (dm-w) of female-heterogametic clawed frogs (Xenopus; ZW♀/ZZ♂), is known across >8740 species of amphibians. In this study, by combining chromosome-scale female and male genomes of a non-model amphibian, the European green toad, Bufo(tes) viridis, with ddRAD- and whole genome pool-sequencing, we reveal a candidate master locus, governing a male-heterogametic system (XX♀/XY♂). Targeted sequencing across multiple taxa uncovered structural X/Y-variation in the 5'-regulatory region of the gene bod1l, where a Y-specific non-coding RNA (ncRNA-Y), only expressed in males, suggests that this locus initiates sex-specific differentiation. Developmental transcriptomes and RNA in-situ hybridization show timely and spatially relevant sex-specific ncRNA-Y and bod1l-gene expression in primordial gonads. This coincided with differential H3K4me-methylation in pre-granulosa/pre-Sertoli cells, pointing to a specific mechanism of amphibian sex determination.

Advanced Research and Development Center for Experimental Medicine CEMEX Grigore T Popa University of Medicine and Pharmacy Mihail Kogălniceanu Street 9 13 Iasi 700259 Romania

Danube Delta National Institute for Research and Development Tulcea 820112 Romania

Department of Biological Sciences and Centre for Bioimaging Sciences National University of Singapore 14 Science Drive 4 Block S1A Level 6 Singapore 117543 Singapore

Department of Biology McMaster University 1280 Main Street West Hamilton L8S 4K1 Ontario ON Canada

Department of Cell Biology Faculty of Science Charles University Viničná 7 Prague 12843 Czech Republic

Department of Ecology and Evolution University of Lausanne Lausanne Switzerland

Department of Molecular Biology and Genetics Genetics Faculty of Science Bilkent University SB Building Ankara 06800 Turkey

Developmental Biochemistry Biocenter University of Wuerzburg Am Hubland 97074 Wuerzburg Germany

Leibniz Institute of Freshwater Ecology and Inland Fisheries IGB Müggelseedamm 301 and 310 12587 Berlin Germany

SIGENAE Plate forme Bio informatique Genotoul Mathématiques et Informatique Appliquées de Toulouse INRAe 31326 Castanet Tolosan France

Swiss Institute of Bioinformatics Lausanne Switzerland

The Xiphophorus Genetic Stock Center Department of Chemistry and Biochemistry Texas State University San Marcos TX 78666 USA

Zobrazit více v PubMed

Herpin A, Schartl M. Plasticity of gene-regulatory networks controlling sex determination: of masters, slaves, usual suspects, newcomers, and usurpators. EMBO Rep. 2015;16:1260–1274. doi: 10.15252/embr.201540667. PubMed DOI PMC

Capel B. Vertebrate sex determination: evolutionary plasticity of a fundamental switch. Nat. Rev. Genet. 2017;18:675–689. doi: 10.1038/nrg.2017.60. PubMed DOI

Bachtrog D, et al. Sex determination: why so many ways of doing it? PLoS Biol. 2014;12:e1001899. doi: 10.1371/journal.pbio.1001899. PubMed DOI PMC

Rovatsos M, et al. Conservation of sex chromosomes in lacertid lizards. Mol. Ecol. 2016;25:3120–3126. doi: 10.1111/mec.13635. PubMed DOI

Beukeboom, L. W. & Perrin, N. The evolution of sex determination (Oxford University Press, 2014).

Volff JN, Nanda I, Schmid M, Schartl M. Governing sex determination in fish: regulatory putsches and ephemeral dictators. Sex. Dev. 2007;1:85–99. doi: 10.1159/000100030. PubMed DOI

Perrin N. Sex reversal: a fountain of youth for sex chromosomes? Evolution. 2009;63:3043–3049. doi: 10.1111/j.1558-5646.2009.00837.x. PubMed DOI

Bertho S, Herpin A, Schartl M, Guiguen Y. Lessons from an unusual vertebrate sex-determining gene. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2021;376:20200092. doi: 10.1098/rstb.2020.0092. PubMed DOI PMC

Kuhl H, et al. A 180 Myr-old female-specific genome region in sturgeon reveals the oldest known vertebrate sex determining system with undifferentiated sex chromosomes. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2021;376:20200089. doi: 10.1098/rstb.2020.0089. PubMed DOI PMC

Kostmann A, Kratochvíl L, Rovatsos M. Poorly differentiated XX/XY sex chromosomes are widely shared across skink radiation. Proc. Biol. Sci. 2021;288:20202139. PubMed PMC

Pan, Q. et al. The rise and fall of the ancient northern pike master sex-determining gene. Elife10, 10.7554/eLife.62858 (2021). PubMed PMC

Ito, M. Sex determination and differentiation in frogs. in Reproductive and Developmental Strategies: The Continuity of Life (eds. Kobayashi, K., Kitano, T., Iwao, Y. & Kondo, M.) 349–366 (Springer Japan, Tokyo, 2018).

Schmid, M. & Steinlein, C. Sex chromosomes, sex-linked genes, and sex determination in the vertebrate class Amphibia. in Genes and Mechanisms in Vertebrate Sex Determination (eds. Scherer, G. & Schmid, M.) 143–176 (Birkhäuser Basel, Basel, 2001). PubMed

Schartl M, Schmid M, Nanda I. Dynamics of vertebrate sex chromosome evolution: from equal size to giants and dwarfs. Chromosoma. 2016;125:553–571. doi: 10.1007/s00412-015-0569-y. PubMed DOI

Green DM. Cytogenetics of the endemic New Zealand frog, Leiopelma hochstetteri: extraordinary supernumerary chromosome variation and a unique sex-chromosome system. Chromosoma. 1988;97:55–70. doi: 10.1007/BF00331795. DOI

Roco Á, et al. Coexistence of Y, W, and Z sex chromosomes in Xenopus tropicalis. Proc. Natl. Acad. Sci. USA. 2015;112:E4752–E4761. doi: 10.1073/pnas.1505291112. PubMed DOI PMC

Furman BLS, et al. 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. 2020;16:e1009121. doi: 10.1371/journal.pgen.1009121. PubMed DOI PMC

AmphibiaWeb. See www.amphibiaweb.org (accessed May 2024).

Yoshimoto S, et al. A W-linked DM-domain gene, DM-W, participates in primary ovary development in Xenopus laevis. Proc. Natl. Acad. Sci. USA. 2008;105:2469–2474. doi: 10.1073/pnas.0712244105. PubMed DOI PMC

Cauret CMS, et al. Developmental systems drift and the drivers of sex chromosome evolution. Mol. Biol. Evol. 2020;37:799–810. doi: 10.1093/molbev/msz268. PubMed DOI

Cauret CMS, et al. Functional dissection and assembly of a small, newly evolved, W chromosome-specific genomic region of the African clawed frog Xenopus laevis. Plos Genet. 2023;19:e1010990. doi: 10.1371/journal.pgen.1010990. PubMed DOI PMC

Evans BJ, et al. New insights into Xenopus sex chromosome genomics from the Marsabit clawed frog X. borealis. J. Evol. Biol. 2022;35:1777–1790. doi: 10.1111/jeb.14078. PubMed DOI PMC

Bogart, J. P. Karyotypes. in Evolution of the genus Bufo (ed. Blair, W. F.) 171–232 (University of Texas Press, 1972).

Schmid M. Chromosome banding in Amphibia I. Constitutive heterochromatin and nucleolus organizer regions in Bufo and Hyla. Chromosoma. 1978;66:361–388. doi: 10.1007/BF00328536. DOI

Piprek RP, Kloc M, Kubiak JZ. Bidder’s organ–structure, development and function. Int. J. Dev. Biol. 2014;58:819–827. doi: 10.1387/ijdb.140147rp. PubMed DOI

Harms W. Untersuchungen über das Biddersche Organ der männlichen und weiblichen Kröten. Z. Anat. Entwickl. Gesch. 1923;69:598–629. doi: 10.1007/BF02593633. DOI

Ponse K. La proportion sexuelle dans la descendance issue des oeufs produits par l’organe de Bidder des crapauds femelles. Rev. Suisse Zool. 1941;48:541–544.

Changxiang W, Qun L, Wei X. Studies of chromosome banding and sister chromatid exchange in Bufo bufo gargarizans. Acta Gen. Sin. 1983;10:291–297.

Abramyan J, Ezaz T, Graves JA, Koopman P. Z and W sex chromosomes in the cane toad (Bufo marinus) Chromosome Res. 2009;17:1015–1024. doi: 10.1007/s10577-009-9095-1. PubMed DOI

Malone JH, Fontenot BE. Patterns of reproductive isolation in toads. PLoS One. 2008;3:e3900. doi: 10.1371/journal.pone.0003900. PubMed DOI PMC

Stöck M, Steinlein C, Lamatsch DK, Schartl M, Schmid M. Multiple origins of tetraploid taxa in the Eurasian Bufo viridis subgroup. Genetica. 2005;124:255–272. doi: 10.1007/s10709-005-3085-9. PubMed DOI

Ueda, H. Offspring of sex-reversed males in Bufo viridis. Sci. Rep. Lab. Amphib. Biol. Hiroshima. Univ. 10, 155–164 (1990).

Stöck M, et al. Low rates of X-Y recombination, not turnovers, account for homomorphic sex chromosomes in several diploid species of Palearctic green toads (Bufo viridis subgroup) J. Evol. Biol. 2013;26:674–682. doi: 10.1111/jeb.12086. PubMed DOI

Brelsford A, et al. Homologous sex chromosomes in three deeply divergent anuran species. Evolution. 2013;67:2434–2440. doi: 10.1111/evo.12151. PubMed DOI

Tamschick S, et al. Sex chromosome conservation, DMRT1 phylogeny and gonad morphology in diploid Palearctic green toads (Bufo viridis subgroup) Cytogenet Genome Res. 2014;144:315–324. doi: 10.1159/000380841. PubMed DOI

Betto-Colliard C, Hofmann S, Sermier R, Perrin N, Stöck M. Profound genetic divergence and asymmetric parental genome contributions as hallmarks of hybrid speciation in polyploid toads. Proc. Biol. Sci. 2018;285:20172667. PubMed PMC

Burgin, C. et al. Mammal Diversity Database (Version 1.12.1) dataset. Zenodo10.5281/zenodo.7830771 (2023) (accessed May 2024: https://www.mammaldiversity.org).

NCBI. See www.ncbi.nlm.nih.gov (accessed May 2024).

Guzmán K, et al. Identification and characterization of a new family of long satellite DNA, specific of true toads (Anura, Amphibia, Bufonidae) Sci. Rep. 2022;12:13960. doi: 10.1038/s41598-022-18051-9. PubMed DOI PMC

Stöck M, et al. Evolution of mitochondrial relationships and biogeography of Palearctic green toads (Bufo viridis subgroup) with insights in their genomic plasticity. Mol. Phylogenet Evol. 2006;41:663–689. doi: 10.1016/j.ympev.2006.05.026. PubMed DOI

Dufresnes C, et al. Phylogeography of Aegean green toads (Bufo viridis subgroup): continental hybrid swarm vs. insular diversification with discovery of a new island endemic. BMC Evol. Biol. 2018;18:67. doi: 10.1186/s12862-018-1179-0. PubMed DOI PMC

Schartl, M. & Herpin, A. Sex determination in vertebrates. in Encyclopedia of Reproduction (2nd Edition) (ed. Skinner, M. K.) 159–167 (Academic Press, 2018).

Gosner KL. A simplified table for staging anuran embryos and larvae with notes on identification. Herpetologica. 1960;16:183–190.

Burren OS, et al. Chromosome contacts in activated T cells identify autoimmune disease candidate genes. Genome Biol. 2017;18:165. doi: 10.1186/s13059-017-1285-0. PubMed DOI PMC

Jackson DA, Dickinson P, Cook PR. The size of chromatin loops in HeLa cells. EMBO J. 1990;9:567–571. doi: 10.1002/j.1460-2075.1990.tb08144.x. PubMed DOI PMC

Lyu J, Shao R, Kwong Yung PY, Elsässer SJ. Genome-wide mapping of G-quadruplex structures with CUT&Tag. Nucleic Acids Res. 2022;50:e13. doi: 10.1093/nar/gkab1073. PubMed DOI PMC

Bayley R, et al. H3K4 methylation by SETD1A/BOD1L facilitates RIF1-dependent NHEJ. Mol. Cell. 2022;82:1924–1939.e10. doi: 10.1016/j.molcel.2022.03.030. PubMed DOI PMC

Giovanni, C. et al. The BOD1L subunit of the mammalian SETD1A complex sustains the expression of DNA damage repair genes despite restraining H3K4 trimethylation. Preprint at https://www.biorxiv.org/content/10.1101/2023.04.06.535882v2 (2023). DOI

Hayashi S, et al. Neofunctionalization of a Noncoding Portion of a DNA Transposon in the Coding Region of the Chimerical Sex-Determining Gene dm-W in Xenopus Frogs. Mol. Biol. Evol. 2022;39:msac138. doi: 10.1093/molbev/msac138. PubMed DOI PMC

Burgos M, et al. Non-coding RNAs: lncRNAs, miRNAs, and piRNAs in sexual development. Sex. Dev. 2021;15:335–350. doi: 10.1159/000519237. PubMed DOI

Joshi M, Rajender S. Long non-coding RNA (lncRNAs) in spermatogenesis, male infertility. Reprod. Biol. Endocrinol. 2020;18:103. doi: 10.1186/s12958-020-00660-6. PubMed DOI PMC

Feng B, et al. lncRNA DMRT2-as acts as a transcriptional regulator of dmrt2 involving in sex differentiation in the Chinese tongue sol (Cynoglossus semilaevis) Comp. Biochem Physiol. B Biochem Mol. Biol. 2021;253:110542. doi: 10.1016/j.cbpb.2020.110542. PubMed DOI

Bowles J, Koopman P. Retinoic acid, meiosis and germ cell fate in mammals. Development. 2007;134:3401–3411. doi: 10.1242/dev.001107. PubMed DOI

Higgs MR, et al. BOD1L is required to suppress deleterious resection of stressed replication forks. Mol. Cell. 2015;59:462–477. doi: 10.1016/j.molcel.2015.06.007. PubMed DOI

Higgs MR, et al. Histone methylation by SETD1A protects nascent DNA through the nucleosome chaperone activity of FANCD2. Mol. Cell. 2018;71:25–41. doi: 10.1016/j.molcel.2018.05.018. PubMed DOI PMC

Rodríguez-Marí A, Postlethwait JH. The role of Fanconi anemia/BRCA genes in zebrafish sex determination. Methods Cell Biol. 2011;105:461–490. doi: 10.1016/B978-0-12-381320-6.00020-5. PubMed DOI

Smallwood SA, Kelsey G. De novo DNA methylation: a germ cell perspective. Trends Genet. 2012;28:33–42. doi: 10.1016/j.tig.2011.09.004. PubMed DOI

Youds JL, Boulton SJ. The choice in meiosis—defining the factors that influence crossover or non-crossover formation. J. Cell Sci. 2011;124:501–513. doi: 10.1242/jcs.074427. PubMed DOI

Ki BS, et al. Epigenetic regulator Cfp1 safeguards male meiotic progression by regulating meiotic gene expression. Exp. Mol. Med. 2022;54:1098–1108. doi: 10.1038/s12276-022-00813-0. PubMed DOI PMC

Fan, H.-Y. & Sun, Q.-Y. Chapter 12 - Oocyte Meiotic Maturation. in The Ovary (3rd Edition) (eds. Leung, P. C. K. & Adashi, E. Y.) 181–203 (Academic Press, 2019).

Dupont S, Capel B. The chromatin state during gonadal sex determination. Sex. Dev. 2021;15:308–316. doi: 10.1159/000520007. PubMed DOI PMC

Garcia-Moreno SA, et al. CBX2 is required to stabilize the testis pathway by repressing Wnt signaling. PLoS Genet. 2019;15:e1007895. doi: 10.1371/journal.pgen.1007895. PubMed DOI PMC

Nakamura M. Sex determination in amphibians. Semin Cell Dev. Biol. 2009;20:271–282. doi: 10.1016/j.semcdb.2008.10.003. PubMed DOI

Wolf JC, et al. Effects of 17β-estradiol exposure on Xenopus laevis gonadal histopathology. Environ. Toxicol. Chem. 2010;29:1091–1105. doi: 10.1002/etc.133. PubMed DOI

Peng Y, Leung HC, Yiu SM, Chin FY. IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth. Bioinformatics. 2012;28:1420–1428. doi: 10.1093/bioinformatics/bts174. PubMed DOI

Ruan J, Li H. Fast and accurate long-read assembly with wtdbg2. Nat. Methods. 2020;17:155–158. doi: 10.1038/s41592-019-0669-3. PubMed DOI PMC

Kolmogorov M, Yuan J, Lin Y, Pevzner PA. Assembly of long, error-prone reads using repeat graphs. Nat. Biotechnol. 2019;37:540–546. doi: 10.1038/s41587-019-0072-8. PubMed DOI

Danecek P, et al. The variant call format and VCFtools. Bioinformatics. 2011;27:2156–2158. doi: 10.1093/bioinformatics/btr330. PubMed DOI PMC

Durand NC, et al. Juicer provides a one-click system for analyzing loop-resolution Hi-C experiments. Cell Syst. 2016;3:95–98. doi: 10.1016/j.cels.2016.07.002. PubMed DOI PMC

Dudchenko O, et al. De novo assembly of the Aedes aegypti genome using Hi-C yields chromosome-length scaffolds. Science. 2017;356:92–95. doi: 10.1126/science.aal3327. PubMed DOI PMC

Durand NC, et al. Juicebox provides a visualization system for Hi-C contact maps with unlimited zoom. Cell Syst. 2016;3:99–101. doi: 10.1016/j.cels.2015.07.012. PubMed DOI PMC

Kent WJ, et al. The human genome browser at UCSC. Genome Res. 2002;12:996–1006. doi: 10.1101/gr.229102. PubMed DOI PMC

Gerchen JF, et al. A single transcriptome of a green toad (Bufo viridis) yields candidate genes for sex determination and -differentiation and non-anonymous population genetic markers. PLoS One. 2016;11:e0156419. doi: 10.1371/journal.pone.0156419. PubMed DOI PMC

Li H. Minimap2: pairwise alignment for nucleotide sequences. Bioinformatics. 2018;34:3094–3100. doi: 10.1093/bioinformatics/bty191. PubMed DOI PMC

Nie Fan, et al. De novo diploid genome assembly using long noisy reads via haplotype-aware error correction and inconsistent overlap identification. Nat. Commun. 2024;15:2964. doi: 10.1038/s41467-024-47349-7. PubMed DOI PMC

Zhang H, et al. Fast alignment and preprocessing of chromatin profiles with Chromap. Nat. Comm. 2021;12:6566. doi: 10.1038/s41467-021-26865-w. PubMed DOI PMC

Zhou C, McCarthy SA, Durbin R. YaHS: yet another Hi-C scaffolding tool. Bioinformatics. 2023;39:btac808. doi: 10.1093/bioinformatics/btac808. PubMed DOI PMC

Kolmogorov M, et al. Chromosome assembly of large and complex genomes using multiple references. Genome Res. 2018;28:1720–1732. doi: 10.1101/gr.236273.118. PubMed DOI PMC

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;116:177–181. doi: 10.1038/hdy.2015.83. PubMed DOI PMC

Rochette NC, Rivera-Colón AG, Catchen JM. Stacks 2: analytical methods for paired-end sequencing improve RADseq-based population genomics. Mol. Ecol. Res. 2019;28:4737–4754. doi: 10.1111/mec.15253. PubMed DOI

Feron R, et al. RADSex: a computational workflow to study sex determination using restriction site-associated DNA sequencing data. Mol. Ecol. Resour. 2021;21:1715–1731. doi: 10.1111/1755-0998.13360. PubMed DOI PMC

https://github.com/RomainFeron/paper-sexdetermination-greentoad-2021.

Li H, et al. The sequence Alignment/Map format and SAMtools. Bioinformatics. 2009;25:2078–2079. doi: 10.1093/bioinformatics/btp352. PubMed DOI PMC

Rimmer A, et al. Integrating mapping-, assembly- and haplotype-based approaches for calling variants in clinical sequencing applications. Nat. Genet. 2014;46:912–918. doi: 10.1038/ng.3036. PubMed DOI PMC

Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010;26:841–842. doi: 10.1093/bioinformatics/btq033. PubMed DOI PMC

Sahlin K, Lim MCW, Prost S. NGSpeciesID: DNA barcode and amplicon consensus generation from long-read sequencing data. Ecol. Evol. 2021;11:1392–1398. doi: 10.1002/ece3.7146. PubMed DOI PMC

Danecek P, et al. Twelve years of SAMtools and BCFtools. Gigascience. 2021;10:giab008. doi: 10.1093/gigascience/giab008. PubMed DOI PMC

Castresana J. Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol. Biol. Evol. 2000;17:540–552. doi: 10.1093/oxfordjournals.molbev.a026334. PubMed DOI

Minh BQ, et al. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol. Biol. Evol. 2020;37:1530–1534. doi: 10.1093/molbev/msaa015. PubMed DOI PMC

Kamran H, Tahir M, Tayara H, Chong KT. iEnhancer-deep: a computational predictor for enhancer sites and their strength using deep learning. Appl. Sci. 2022;12:2120. doi: 10.3390/app12042120. DOI

Tamschick S, et al. Sex reversal assessments reveal different vulnerability to endocrine disruption between deeply diverged anuran lineages. Sci. Rep. 2016;6:23825. doi: 10.1038/srep23825. PubMed DOI PMC

Liao Y, Smyth GK, Shi W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2014;30:923–930. doi: 10.1093/bioinformatics/btt656. PubMed DOI

Dasyani M, et al. Lineage tracing of col10a1 cells identifies distinct progenitor populations for osteoblasts and joint cells in the regenerating fin of medaka (Oryzias latipes) Dev. Biol. 2019;455:85–99. doi: 10.1016/j.ydbio.2019.07.012. PubMed DOI

Knytl, M. & Fornaini, N. R. Measurement of chromosomal arms and FISH reveal complex genome architecture and standardized karyotype of model fish, genus Carassius. Cells10, 10.3390/cells10092343 (2021). PubMed PMC

Courtet M, Flajnik M, Du Pasquier L. Major histocompatibility complex and immunoglobulin loci visualized by in situ hybridization on Xenopus chromosomes. Dev. Comp. Immunol. 2001;25:149–157. doi: 10.1016/S0145-305X(00)00045-8. PubMed DOI

Krylov V, Tlapakova T, Macha J. Localization of the single copy gene Mdh2 on Xenopus tropicalis chromosomes by FISH-TSA. Cytogenet Genome Res. 2007;116:110–112. doi: 10.1159/000097427. PubMed DOI

Knytl M, Tlapakova T, Vankova T, Krylov V. Silurana chromosomal evolution: a new piece to the puzzle. Cytogenet Genome Res. 2018;156:223–228. doi: 10.1159/000494708. PubMed DOI

Seroussi E, et al. Avian expression patterns and genomic mapping implicate leptin in digestion and TNF in immunity, suggesting that their interacting adipokine role has been acquired only in mammals. Int J. Mol. Sci. 2019;20:4489. doi: 10.3390/ijms20184489. PubMed DOI PMC

Mirdita M, et al. ColabFold: making protein folding accessible to all. Nat. Methods. 2022;19:679–682. doi: 10.1038/s41592-022-01488-1. PubMed DOI PMC

Peng J, Xu J. RaptorX: exploiting structure information for protein alignment by statistical inference. Proteins. 2011;79:161–171. doi: 10.1002/prot.23175. PubMed DOI PMC

Wang J, et al. iCn3D, a web-based 3D viewer for sharing 1D/2D/3D representations of biomolecular structures. Bioinformatics. 2020;36:131–135. doi: 10.1093/bioinformatics/btz502. PubMed DOI PMC

FISH mapping in Xenopus pygmaeus refines understanding of genomic rearrangements and reveals jumping NORs in African clawed frogs

Rapid Sex Chromosome Turnover in African Clawed Frogs (Xenopus) and the Origins of New Sex Chromosomes