- Physical Review Journals
All JournalsPhysics Magazine

PRX Life

Reuse & Permissions

It is not necessary to obtain permission to reuse this article or its components as it is available under the terms of the Creative Commons Attribution 4.0 International license. This license permits unrestricted use, distribution, and reproduction in any medium, provided attribution to the author(s) and the published article's title, journal citation, and DOI are maintained. Please note that some figures may have been included with permission from other third parties. It is your responsibility to obtain the proper permission from the rights holder directly for these figures.

Export citation

Export citation

Choose format for download:

Download Citation
  • Open Access

Coarsening Model of Chromosomal Crossover Placement

Marcel Ernst*, Riccardo Rossetto, and David Zwicker†

  • *Contact author: marcel.ernst@ds.mpg.de
  • †Contact author: david.zwicker@ds.mpg.de
PDF

PRX Life 4, 013033 – Published 11 March, 2026

DOI: https://doi.org/10.1103/8jrt-rb28

Abstract

Chromosomal crossovers play a crucial role in meiotic cell division, as they ensure proper chromosome segregation and increase genetic variability. Experiments have consistently revealed two key observations across species: (i) the number of crossovers per chromosome is typically small, but at least one, and (ii) crossovers on the same chromosome are subject to interference, i.e., they are more separated than expected by chance. These observations can be explained by a recently proposed coarsening model, where the dynamics of droplets associated with chromosomes designate crossovers. We here introduce an extended coarsening model, which includes material exchanges between droplets, the synaptonemal complex, and the nucleoplasm. Using a comprehensive analysis, including scaling laws for the crossover count, allows us to analyze data across species. Moreover, our model provides a coherent explanation of experimental data across mutants, including the wild type and zyp1 mutant of Arabidopsis thaliana. Consequently, the extended coarsening model provides a solid framework for investigating the underlying mechanisms of crossover placement.

View figure in article

Physics Subject Headings (PhySH)

Collections

This article appears in the following collection:

Collection on Physics of Biomolecular Condensates

From the fundamentals of phase separation, dynamics and structure of condensates in biological settings, to advanced imaging methods, this special collection presented by PRX Life showcases exciting and timely work on the physics of biomolecular condensates.

This Invited Collection is coordinated by PRX Life Associate Editor Christoph Weber, in consultation with Jerelle Joseph, Simon Alberti, and Tanja Mittag. Every article published in this collection underwent a rigorous peer review process, adhering to the same high standards applied to all papers handled by the journal. The PRX Life editorial team managed the peer review and made all editorial decisions.

Article Text

Supplemental Material

References (77)

  1. L. E. Berchowitz and G. P. Copenhaver, Genetic interference: don't stand so close to me, Curr. Genomics 11, 91 (2010).
  2. S. T. Globus and S. Keeney, The joy of six: How to control your crossovers, Cell 149, 11 (2012).
  3. L. K. Anderson, L. D. Lohmiller, X. Tang, D. B. Hammond, L. Javernick, L. Shearer, S. Basu-Roy, O. C. Martin, and M. Falque, Combined fluorescent and electron microscopic imaging unveils the specific properties of two classes of meiotic crossovers, Proc. Natl. Acad. Sci. USA 111, 13415 (2014).
  4. S. Wang, D. Zickler, N. Kleckner, and L. Zhang, Meiotic crossover patterns: obligatory crossover, interference and homeostasis in a single process, Cell Cycle 14, 305 (2015).
  5. D. Zickler and N. Kleckner, A few of our favorite things: Pairing, the bouquet, crossover interference and evolution of meiosis, Semin. Cell Dev. Biol. 54, 135 (2016).
  6. S. P. Otto and B. A. Payseur, Crossover interference: Shedding light on the evolution of recombination, Annu. Rev. Genet. 53, 19 (2019).
  7. G. R. Smith and M. Nambiar, New solutions to old problems: molecular mechanisms of meiotic crossover control, Trends Genet. 36, 337 (2020).
  8. G. H. Jones, The control of chiasma distribution, Symp. Soc. Exp. Biol. 38, 293 (1984).
  9. G. V. Börner, N. Kleckner, and N. Hunter, Crossover/ noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis, Cell 117, 29 (2004).
  10. L. von Diezmann and O. Rog, Let's get physical—mechanisms of crossover interference, J. Cell Sci. 134, jcs255745 (2021).
  11. A. Lloyd, Crossover patterning in plants, Plant Reprod. 36, 55 (2023).
  12. C. Girard, D. Zwicker, and R. Mercier, The regulation of meiotic crossover distribution: A coarse solution to a century-old mystery? Biochem. Soc. Trans. 51, 1179 (2023).
  13. F. Cole, L. Kauppi, J. Lange, I. Roig, R. Wang, S. Keeney, and M. Jasin, Homeostatic control of recombination is implemented progressively in mouse meiosis, Nat. Cell Biol. 14, 424 (2012).
  14. D. Zickler and N. Kleckner, Recombination, pairing, and synapsis of homologs during meiosis, Cold Spring Harbor Perspect. Biol. 7, a016626 (2015).
  15. J. B. Fernandes, M. Séguéla-Arnaud, C. Larchevêque, A. H. Lloyd, and R. Mercier, Unleashing meiotic crossovers in hybrid plants, Proc. Natl. Acad. Sci. USA 115, 2431 (2018).
  16. A. H. Sturtevant, The linear arrangement of six sex-linked factors in Drosophila, as shown by their mode of association, J. Exp. Zool. 14, 43 (1913).
  17. A. H. Sturtevant, The behavior of the chromosomes as studied through linkage, Z. Indukt. Abstamm.- Vererbungsl. 13, 234 (1915).
  18. H. J. Muller, The mechanism of crossing-over, Am. Nat. 50, 193 (1916).
  19. N. Kleckner, A. Storlazzi, and D. Zickler, Coordinate variation in meiotic pachytene SC length and total crossover/chiasma frequency under conditions of constant DNA length, Trends Genet. 19, 623 (2003).
  20. A. T. Carpenter, Electron microscopy of meiosis in Drosophila melanogaster females: I. Structure, arrangement, and temporal change of the synaptonemal complex in wild-type, Chromosoma 51, 157 (1975).
  21. D. Zickler and N. Kleckner, Meiotic chromosomes: Integrating structure and function, Annu. Rev. Genet. 33, 603 (1999).
  22. S. L. Page and R. S. Hawley, The genetics and molecular biology of the synaptonemal complex, Annu. Rev. Cell Dev. Biol. 20, 525 (2004).
  23. L. Capilla-Pérez, S. Durand, A. Hurel, Q. Lian, A. Chambon, C. Taochy, V. Solier, M. Grelon, and R. Mercier, The synaptonemal complex imposes crossover interference and heterochiasmy in Arabidopsis, Proc. Natl. Acad. Sci. USA 118, e2023613118 (2021).
  24. W. T. Stauffer, L. Zhang, and A. Dernburg, Diffusion through a liquid crystalline compartment regulates meiotic recombination, Proc. SPIE 10888, 1088809 (2019).
  25. O. Rog, S. Köhler, and A. F. Dernburg, The synaptonemal complex has liquid crystalline properties and spatially regulates meiotic recombination factors, eLife 6, e21455 (2017).
  26. S. Wang, Y. Liu, Y. Shang, B. Zhai, X. Yang, N. Kleckner, and L. Zhang, Crossover interference, crossover maturation, and human aneuploidy, BioEssays 41, 1800221 (2019).
  27. S. Neyton, F. Lespinasse, P. B. Moens, R. Paul, P. Gaudray, V. Paquis-Flucklinger, and S. Santucci-Darmanin, Association between MSH4 (MUTS homologue 4) and the DNA strand-exchange RAD51 and DMC1 proteins during mammalian meiosis, Mol. hum. reprod. 10, 917 (2004).
  28. F. Baudat and B. de Massy, Regulating double-stranded DNA break repair towards crossover or non-crossover during mammalian meiosis, Chromosome Res. 15, 565 (2007).
  29. N. M. Hollingsworth and S. J. Brill, The MUS81 solution to resolution: Generating meiotic crossovers without holliday junctions, Genes Dev. 18, 117 (2004).
  30. L. Zhang, Z. Liang, J. Hutchinson, and N. Kleckner, Crossover patterning by the beam-film model: Analysis and implications, PLoS Genet. 10, e1004042 (2014).
  31. N. Kleckner, D. Zickler, G. H. Jones, J. Dekker, R. Padmore, J. Henle, and J. Hutchinson, A mechanical basis for chromosome function, Proc. Natl. Acad. Sci. USA 101, 12592 (2004).
  32. J. S. King and R. Mortimer, A polymerization model of chiasma interference and corresponding computer simulation, Genetics 126, 1127 (1990).
  33. L. Zhang, S. Köhler, R. Rillo-Bohn, and A. F. Dernburg, A compartmentalized signaling network mediates crossover control in meiosis, eLife 7, e30789 (2018).
  34. S. Durand, Q. Lian, J. Jing, M. Ernst, M. Grelon, D. Zwicker, and R. Mercier, Joint control of meiotic crossover patterning by the synaptonemal complex and HEI10 dosage, Nat. Commun. 13, 5999 (2022).
  35. C. Morgan, J. A. Fozard, M. Hartley, I. R. Henderson, K. Bomblies, and M. Howard, Diffusion-mediated HEI10 coarsening can explain meiotic crossover positioning in Arabidopsis, Nat. Commun. 12, 4674 (2021).
  36. L. Zhang, W. Stauffer, C. Liu, H. Shao, N. Abuzahriyeh, R. Jiang, D. Zwicker, X. Liu, X. Yao, and A. F. Dernburg, Crossover patterning through condensation and coarsening of pro-crossover factors, Nat. Cell. Biol. 27, 1161 (2025).
  37. P. A. Ziolkowski, C. J. Underwood, C. Lambing, M. Martinez-Garcia, E. J. Lawrence, L. Ziolkowska, C. Griffin, K. Choi, F. C. H. Franklin, R. A. Martienssen, et al., Natural variation and dosage of the HEI10 meiotic E3 ligase control Arabidopsis crossover recombination, Genes Dev. 31, 306 (2017).
  38. M. Sym and G. Roeder, Crossover interference is abolished in the absence of a synaptonemal complex protein, Cell 79, 283 (1994).
  39. J. A. Fozard, C. Morgan, M. Howard, A. Shinohara, and D. Weigel, Coarsening dynamics can explain meiotic crossover patterning in both the presence and absence of the synaptonemal complex, eLife 12, e79408 (2023).
  40. E. Martini, R. L. Diaz, N. Hunter, and S. Keeney, Crossover homeostasis in yeast meiosis, Cell 126, 285 (2006).
  41. T. Wang, H. Wang, Q. Lian, Q. Jia, C. You, G. P. Copenhaver, C. Wang, and Y. Wang, HEI10 is subject to phase separation and mediates RPA1A degradation during meiotic interference-sensitive crossover formation, Proc. Natl. Acad. Sci. USA 120, e2310542120 (2023).
  42. H. Kim, J. Kim, N. Son, P. Kuo, C. Morgan, A. Chambon, D. Byun, J. Park, Y. Lee, Y. M. Park, et al., Control of meiotic crossover interference by a proteolytic chaperone network, Nat. Plants 10, 453 (2024).
  43. L. Zhang, W. Stauffer, C. Liu, H. Shao, N. Abuzahriyeh, R. Jiang, D. Zwicker, X. Liu, X. Yao, and A. F. Dernburg, Crossover patterning through condensation and coarsening of pro-crossover factors, Nat. Cell Biol. 27, 1161 (2025).
  44. R. Rossetto, M. Ernst, and D. Zwicker, Exchange controls coarsening of surface condensates, arXiv:2511.03619.
  45. D. Zwicker, O. Paulin, and C. ter Burg, Physics of droplet regulation in biological cells, Rep. Prog. Phys. 88, 116601 (2025).
  46. J. Söding, D. Zwicker, S. Sohrabi-Jahromi, M. Boehning, and J. Kirschbaum, Mechanisms for active regulation of biomolecular condensates, Trends Cell Biol. 30, 4 (2020).
  47. J. Kirschbaum and D. Zwicker, Controlling biomolecular condensates via chemical reactions, J. R. Soc. Interface. 18, 20210255 (2021).
  48. Y. Cho and W. M. Jacobs, Interfacial effects determine nonequilibrium phase behaviors in chemically driven fluids, Proc. Natl. Acad. Sci. USA 122, e2501145122 (2025).
  49. C. A. Weber, D. Zwicker, F. Jülicher, and C. F. Lee, Physics of active emulsions, Rep. Prog. Phys. 82, 064601 (2019).
  50. P. W. Voorhees, Ostwald ripening of two-phase mixtures, Annu. Rev. Mater. Sci. 22, 197 (1992).
  51. F. Jülicher, A. Ajdari, and J. Prost, Modeling molecular motors, Rev. Mod. Phys. 69, 1269 (1997).
  52. M. Z. Bazant, Theory of chemical kinetics and charge transfer based on nonequilibrium thermodynamics, Acc. Chem. Res. 46, 1144 (2013).
  53. P. W. Atkins, J. De Paula, and J. Keeler, Atkins' Physical Chemistry (Oxford University Press, Oxford, UK, 2023).
  54. P. Hänggi, P. Talkner, and M. Borkovec, Reaction-rate theory: Fifty years after kramers, Rev. Mod. Phys. 62, 251 (1990).
  55. F. Jülicher and C. A. Weber, Droplet physics and intracellular phase separation, Annu. Rev. Condens. Matter Phys. 15, 237 (2024).
  56. D. Zwicker, The intertwined physics of active chemical reactions and phase separation, Curr. Opin. Colloid Interface Sci. 61, 101606 (2022).
  57. J. Bauermann, C. A. Weber, and F. Jülicher, Energy and matter supply for active droplets, Ann. Phys. 534, 2200132 (2022).
  58. C. Wagner, Theorie der Alterung von Niederschlägen durch Umlösen (Ostwald‐Reifung), Z. Elektrochem. 65, 581 (1961).
  59. A. W. Folkmann, A. Putnam, C. F. Lee, and G. Seydoux, Regulation of biomolecular condensates by interfacial protein clusters, Science 373, 1218 (2021).
  60. Y. Zhang, A. G. Pyo, R. Kliegman, Y. Jiang, C. P. Brangwynne, H. A. Stone, and N. S. Wingreen, The exchange dynamics of biomolecular condensates, eLife 12, RP91680 (2024).
  61. I. M. Lifshitz and V. V. Slyozov, The kinetics of precipitation from supersaturated solid solutions, J. Phys. Chem. Solids 19, 35 (1961).
  62. See Supplemental Material at http://link.aps.org/supplemental/10.1103/8jrt-rb28 for theoretical details and numerical methods, including Refs. [76, 77].
  63. M. Ernst, R. Mercier, and D. Zwicker, Interference length reveals regularity of crossover placement across species, Nat. Commun. 15, 8973 (2024).
  64. A. Hald, A. de Moivre, and B. McClintock, A. de moivre: 'de mensura sortis' or 'on the measurement of chance', Int. Stat. Rev. 52, 229 (1984).
  65. A. de Moivre, De mensura sortis, seu, de probabilitate eventuum in ludis a casu fortuito pendentibus, Philos. Trans. R. Soc. London 27, 213 (1711).
  66. P. Erdős and A. Rényi, On a classical problem of probability theory, Magyar Tud. Akad. Mat. Kutató Int. Közl 6, 215 (1961).
  67. A. T. C. Carpenter, Normal synaptonemal complex and abnormal recombination nodules in two alleles of the drosophila meiotic mutant mei-w68, Genetics 163, 1337 (2003).
  68. M. A. Prusicki, E. M. Keizer, R. P. van Rosmalen, S. Komaki, F. Seifert, K. Müller, E. Wijnker, C. Fleck, and A. Schnittger, Live cell imaging of meiosis in Arabidopsis thaliana, eLife 8, e42834 (2019).
  69. B. Hu, M. A. Prusicki, K. Stahlmann, Y. Wang, and A. Schnittger, A cytological framework of female meiosis in Arabidopsis, bioRxiv (2025), https://doi.org/10.1101/2025.08.22.671760.
  70. N. Ziethen, J. Kirschbaum, and D. Zwicker, Nucleation of chemically active droplets, Phys. Rev. Lett. 130, 248201 (2023).
  71. S. Rosu, D. E. Libuda, and A. M. Villeneuve, Robust crossover assurance and regulated interhomolog access maintain meiotic crossover number, Science 334, 1286 (2011).
  72. M. Xue, J. Wang, L. Jiang, M. Wang, S. Wolfe, W. P. Pawlowski, Y. Wang, and Y. He, The number of meiotic double-strand breaks influences crossover distribution in Arabidopsis, Plant Cell 30, 2628 (2018).
  73. J. Jing, Q. Lian, S. Durand, and R. Mercier, Maximizing meiotic crossover rates reveals the map of crossover potential, Nat. Commun. 16, 5306 (2025).
  74. V. Borde and B. de Massy, Programmed induction of dna double strand breaks during meiosis: Setting up communication between DNA and the chromosome structure, Curr. Opin. Genet. Dev. 23, 147 (2013).
  75. M. Ernst and D. Zwicker, marcelernst/paper-coarsening-model: Release v1.0.0, Zenodo (2026), https://doi.org/10.5281/zenodo.18593493.
  76. P. Flajolet, D. Gardy, and L. Thimonier, Birthday paradox, coupon collectors, caching algorithms and self-organizing search, Discrete Appl. Math. 39, 207 (1992).
  77. S. Ilie, K. R. Jackson, and W. H. Enright, Adaptive time-stepping for the strong numerical solution of stochastic differential equations, Numer. Algorithms 68, 791 (2015).

Outline

Information

PRX Life 4, 013033– Published 11 March, 2026
  • Received 11 September 2025
  • Accepted 30 January 2026
Crossmark - Check for updates button
Creative Commons Logo

Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI. Open access publication funded by Max Planck Society.

Published by the American Physical Society

Sign In to Your Journals Account

Filter

Filter

Article Lookup

Enter a citation