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Permissive aggregative group formation favors coexistence between cooperators and defectors in yeast

Abstract

In Saccharomyces cerevisiae, the FLO1 gene encodes flocculins that lead to formation of multicellular flocs, that offer protection to the constituent cells. Flo1p was found to preferentially bind to fellow cooperators compared to defectors lacking FLO1 expression, enriching cooperators within the flocs. Given this dual function in cooperation and kin recognition, FLO1 has been termed a “green beard gene”. Because of the heterophilic nature of the Flo1p bond however, we hypothesize that kin recognition is permissive and depends on the relative stability of the FLO1+/flo1 versus FLO1+/FLO1+ detachment force F. We combine single-cell measurements of adhesion, individual cell-based simulations of cluster formation, and in vitro flocculation to study the impact of relative bond stability on the evolutionary stability of cooperation. We identify a trade-off between both aspects of the green beard mechanism, with reduced relative bond stability leading to increased kin recognition at the expense of cooperative benefits. We show that the fitness of FLO1 cooperators decreases as their frequency in the population increases, arising from the observed permissive character (F+− = 0.5 F++) of the Flo1p bond. Considering the costs associated with FLO1 expression, this asymmetric selection often results in a stable coexistence between cooperators and defectors.

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Fig. 1: Mechanical measurement of Flo1p bond properties and mixing predictions.
Fig. 2: Effect of shear on heterotypic Flo1p-dependent flocculation.
Fig. 3: Population dynamics in FLO1 cooperation.
Fig. 4: Effect of Flo1p bond properties on evolutionary stability.

Data availability

Data from the single-cell force spectroscopy and flocculation assay have been made available. The simulation code and framework have been made publicly available at https://doi.org/10.5281/zenodo.6472861.

References

  1. Szathmáry E. Toward major evolutionary transitions theory 2.0. Proc Natl Acad Sci USA. 2015;112:10104–11. https://doi.org/10.1073/pnas.1421398112

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Niklas KJ, Newman SA. The origins of multicellular organisms. Evol Dev. 2013;15:41–52. https://doi.org/10.1111/ede.12013

    Article  PubMed  Google Scholar 

  3. Pfeiffer T, Bonhoeffer S. An evolutionary scenario for the transition to undifferentiated multicellularity. Proc Natl Acad Sci USA. 2003;100:1095–8. https://doi.org/10.1073/pnas.0335420100

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Fisher RM, Regenberg B, Multicellular group formation in Saccharomyces cerevisiae. Proc Royal Soc B: Biol Sci. 2019;286. https://doi.org/10.1098/rspb.2019.1098

  5. Umen JG. Green algae and the origins of multicellularity in the plant kingdom. Cold Spring Harb Perspect Biol. 2014;6:a016170 https://doi.org/10.1101/cshperspect.a016170

    Article  PubMed  PubMed Central  Google Scholar 

  6. Knoll AH. The multiple origins of complex multicellularity. Annu Rev Earth Planet Sci. 2011;39:217–39. https://doi.org/10.1146/annurev.earth.031208.100209

    CAS  Article  Google Scholar 

  7. Bonner JT. The origins of multicellularity. Integr Biol Issues N. Rev. 1998;1:27–36.

    Article  Google Scholar 

  8. Tarnita CE, Taubes CH, Nowak MA. Evolutionary construction by staying together and coming together. J Theor Biol. 2013;320:10–22. https://doi.org/10.1016/j.jtbi.2012.11.022

    Article  PubMed  Google Scholar 

  9. Ratcliff WC, Denison RF, Borrello M, Travisano M. Experimental evolution of multicellularity. Proc Natl Acad Sci USA. 2012;109:1595–1600. https://doi.org/10.1073/pnas.1115323109

    Article  PubMed  PubMed Central  Google Scholar 

  10. Koschwanez JH, Foster KR, Murray AW. Sucrose utilization in budding yeast as a model for the origin of undifferentiated multicellularity. PLoS Biol. 2011;9:e1001122 https://doi.org/10.1371/journal.pbio.1001122

    CAS  Article  PubMed  Google Scholar 

  11. Kuzdzal-Fick JJ, Chen L, Balázsi G. Disadvantages and benefits of evolved unicellularity versus multicellularity in budding yeast. Ecol Evol. 2019;9:8509–23. https://doi.org/10.1002/ece3.5322

    Article  PubMed  PubMed Central  Google Scholar 

  12. Brückner S, Schubert R, Kraushaar T, Hartmann R, Hoffmann D, Jelli E, et al. Kin discrimination in social yeast is mediated by cell surface receptors of the flo11 adhesin family. eLife 2020;9. https://doi.org/10.7554/eLife.55587

  13. Smukalla S, Caldara M, Pochet N, Beauvais A, Guadagnini S, Yan C, et al. FLO1 is a variable green beard gene that drives biofilm-like cooperation in budding yeast. Cell. 2008;135:726–37. https://doi.org/10.1016/j.cell.2008.09.037

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Driscoll WW, Travisano M, Synergistic cooperation promotes multicellular performance and unicellular free-rider persistence. Nat Commun. 2017;8. https://doi.org/10.1038/ncomms15707

  15. Pentz JT, Márquez-Zacarías P, Bozdag GO, Burnetti A, Yunker PJ, Libby E, et al. Ecological advantages and evolutionary limitations of aggregative multicellular development. Curr Biol. 2020;30:4155–.e6. https://doi.org/10.1016/j.cub.2020.08.006.

    CAS  Article  PubMed  Google Scholar 

  16. Goossens K, Willaert R. Flocculation protein structure and cell-cell adhesion mechanism in Saccharomyces cerevisiae. Biotechnol Lett. 2010;32:1571–85. https://doi.org/10.1007/s10529-010-0352-3

    CAS  Article  PubMed  Google Scholar 

  17. Di Gianvito P, Tesnière C, Suzzi G, Blondin B, Tofalo R. FLO5 gene controls flocculation phenotype and adhesive properties in a Saccharomyces cerevisiae sparkling wine strain. Sci Rep. 2017;7:1–12. https://doi.org/10.1038/s41598-017-09990-9

    CAS  Article  Google Scholar 

  18. Veelders M, Brückner S, Ott D, Unverzagt C, Mösch HU, Essen LO. Structural basis of flocculin-mediated social behavior in yeast. Proc Natl Acad Sci USA. 2010;107:22511–6. https://doi.org/10.1073/pnas.1013210108

    Article  PubMed  PubMed Central  Google Scholar 

  19. Verstrepen KJ, Jansen A, Lewitter F, Fink GR. Intragenic tandem repeats generate functional variability. Nat Genet. 2005;37:986–90. https://doi.org/10.1038/ng1618

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Verstrepen KJ, Klis FM. Flocculation, adhesion and biofilm formation in yeasts. Mol Microbiol. 2006;60:5–15. https://doi.org/10.1111/j.1365-2958.2006.05072.x

    CAS  Article  PubMed  Google Scholar 

  21. Verstrepen KJ, Reynolds TB, Fink GR. Origins of variation in the fungal cell surface. Nat Rev Microbiol. 2004;2:533–40. https://doi.org/10.1038/nrmicro927

    CAS  Article  PubMed  Google Scholar 

  22. Kraushaar T, Brückner S, Veelders M, Rhinow D, Schreiner F, Birke R, et al. Interactions by the fungal Flo11 adhesin depend on a fibronectin type III-like adhesin domain girdled by aromatic bands. Structure. 2015;23:1005–17. https://doi.org/10.1016/j.str.2015.03.021

    CAS  Article  PubMed  Google Scholar 

  23. Chen L, Noorbakhsh J, Adams RM, Samaniego-Evans J, Agollah G, Nevozhay D, et al. Two-dimensionality of yeast colony expansion accompanied by pattern formation. PLoS Comput Biol. 2014;10. https://doi.org/10.1371/journal.pcbi.1003979

  24. Oppler ZJ, Parrish ME, Murphy HA, Variation at an adhesin locus suggests sociality in natural populations of the yeast saccharomyces cerevisiae. Proc Royal Soc B: Biol Sci. 2019;286. https://doi.org/10.1098/rspb.2019.1948

  25. Lo WS, Dranginis AM. The cell surface flocculin Flo11 is required for pseudohyphae formation and invasion by Saccharomyces cerevisiae. Mol Biol Cell. 1998;9:161–71. https://doi.org/10.1091/mbc.9.1.161

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. El-Kirat-Chatel S, Beaussart A, Vincent SP, Abellán Flos M, Hols P, Lipke PN, et al. Forces in yeast flocculation. Nanoscale. 2015;7:1760–7. https://doi.org/10.1039/c4nr06315e

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Kobayashi O, Hayashi N, Kuroki R, Sone H. Region of Flo1 proteins responsible for sugar recognition. J Bacteriol. 1998;180:6503–10. https://doi.org/10.1128/jb.180.24.6503-6510.1998

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. Kapsetaki SE, West SA. The costs and benefits of multicellular group formation in algae. Evolution. 2019;73:1296–308. https://doi.org/10.1111/evo.13712

    Article  PubMed  Google Scholar 

  29. Quintero-Galvis JF, Paleo-López R, Solano-Iguaran JJ, Poupin MJ, Ledger T, Gaitan-Espitia JD, et al. Exploring the evolution of multicellularity in Saccharomyces cerevisiae under bacteria environment: An experimental phylogenetics approach. Ecol Evol. 2018;8:4619–30. https://doi.org/10.1002/ece3.3979

    Article  PubMed  PubMed Central  Google Scholar 

  30. Goossens KV, Ielasi FS, Nookaew I, Stals I, Alonso-Sarduy L, Daenen L, et al. Molecular mechanism of flocculation self-recognition in yeast and its role in mating and survival. mBio. 2015;6:1–16. https://doi.org/10.1128/mBio.00427-15

    CAS  Article  Google Scholar 

  31. Hamilton WD. The genetical evolution of social behaviour. I. J Theor Biol. 1964;7:1–16. https://doi.org/10.1016/0022-5193(64)90038-4

    CAS  Article  PubMed  Google Scholar 

  32. Queller DC, Ponte E, Bozzaro S, Strassmann JE. Single-gene greenbeard effects in the social amoeba Dictyostelium discoideum. Science. 2003;299:105–6. https://doi.org/10.1126/science.1077742

    CAS  Article  PubMed  Google Scholar 

  33. Foty RA, Steinberg MS. The differential adhesion hypothesis: A direct evaluation. Dev Biol. 2005;278:255–63. https://doi.org/10.1016/j.ydbio.2004.11.012

    CAS  Article  PubMed  Google Scholar 

  34. Nowak MA. Five rules for the evolution of cooperation. Science. 2006;314:1560–3. https://doi.org/10.1126/science.1133755

    Article  PubMed  PubMed Central  Google Scholar 

  35. Nadell CD, Foster KR, Xavier JB. Emergence of spatial structure in cell groups and the evolution of cooperation. PLoS Comput Biol. 2010;6:e1000716 https://doi.org/10.1371/journal.pcbi.1000716

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. Drescher K, Nadell CD, Stone HA, Wingreen NS, Bassler BL. Solutions to the public goods dilemma in bacterial biofilms. Curr Biol. 2014;24:50–55. https://doi.org/10.1016/j.cub.2013.10.030

    CAS  Article  PubMed  Google Scholar 

  37. Liu CG, Li ZY, Hao Y, Xia J, Bai FW, Mehmood MA, Computer simulation elucidates yeast flocculation and sedimentation for efficient industrial fermentation. Biotechnol J. 2018;13. https://doi.org/10.1002/biot.201700697

  38. Boraas ME, Seale DB, Boxhorn JE. Phagotrophy by flagellate selects for colonial prey: A possible origin of multicellularity. Evol Ecol. 1998;12:153–64. https://doi.org/10.1023/A:1006527528063

    Article  Google Scholar 

  39. Staps M, van Gestel J, Tarnita CE. Emergence of diverse life cycles and life histories at the origin of multicellularity. Nat Ecol Evol. 2019;3:1197–205. https://doi.org/10.1038/s41559-019-0940-0

    Article  PubMed  Google Scholar 

  40. De Vargas Roditi L, Boyle KE, Xavier JB. Multilevel selection analysis of a microbial social trait. Mol Syst Biol. 2013;9:684 https://doi.org/10.1038/msb.2013.42

    Article  PubMed  PubMed Central  Google Scholar 

  41. Damore JA, Gore J. Understanding microbial cooperation. J Theor Biol. 2012;299:31–41. https://doi.org/10.1016/j.jtbi.2011.03.008

    Article  PubMed  Google Scholar 

  42. Denoth Lippuner A, Julou T, Barral Y. Budding yeast as a model organism to study the effects of age. FEMS Microbiol Rev. 2014;38:300–25. https://doi.org/10.1111/1574-6976.12060

    CAS  Article  PubMed  Google Scholar 

  43. Janssens GE, Veenhoff LM. The natural variation in lifespans of single yeast cells is related to variation in cell size, ribosomal protein, and division time. PLoS ONE. 2016;11:e0167394 https://doi.org/10.1371/journal.pone.0167394

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. Ross-Gillespie A, Gardner A, West SA, Griffin AS. Frequency dependence and cooperation: Theory and a test with bacteria. Am Nat. 2007;170:331–42. https://doi.org/10.1086/519860

    Article  PubMed  Google Scholar 

  45. Healey D, Axelrod K, Gore J. Negative frequency-dependent interactions can underlie phenotypic heterogeneity in a clonal microbial population. Mol Syst Biol. 2016;12:877 https://doi.org/10.15252/msb.20167033

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  46. Harrow GL, Lees JA, Hanage WP, Lipsitch M, Corander J, Colijn C, et al. Negative frequency-dependent selection and asymmetrical transformation stabilise multi-strain bacterial population structures. ISME J. 2021;15:1523–38. https://doi.org/10.1038/s41396-020-00867-w

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. Avilés L. Solving the freeloaders paradox: Genetic associations and frequency-dependent selection in the evolution of cooperation among nonrelatives. Proc Natl Acad Sci USA. 2002;99:14268–73. https://doi.org/10.1073/pnas.212408299

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. Fisher RM, Cornwallis CK, West SA. Group formation, relatedness, and the evolution of multicellularity. Curr Biol. 2013;23:1120–5. https://doi.org/10.1016/j.cub.2013.05.004

    CAS  Article  PubMed  Google Scholar 

  49. Pentz JT, Travisano M, Ratcliff WC, Clonal development is evolutionarily superior to aggregation in wild-collected Saccharomyces cerevisiae. In Artificial Life 14 - Proceedings of the 14th International Conference on the Synthesis and Simulation of Living Systems, ALIFE 2014, 2014;550–4. 10.7551/978-0-262-32621-6-ch088.

  50. Melbinger A, Cremer J, Frey E, The emergence of cooperation from a single mutant during microbial life cycles. J Royal Soc Interface. 2015;12. https://doi.org/10.1098/rsif.2015.0171

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Acknowledgements

The authors thank Karin Voordeckers for providing us with the yeast strains; Carmen Bartic and Olivier Deschaume for expertise and support with the SCFS experiments. This work was supported by the KU Leuven Research Fund (CELSA/18/031,C24/18/046). B.S. acknowledges support from the Research Foundation Flanders (FWO) grant 12Z6118N. Research in the lab of K.J.V. is supported by KU Leuven, Vlaams Instituut voor Biotechnologie (VIB) and FWO.

Funding

This work was supported by the KU Leuven Research Fund (CELSA/18/031, C24/18/046). BS acknowledges support from the Research Foundation Flanders (FWO) grant 12Z6118N. Research in the lab of KJV is supported by KU Leuven, Vlaams Instituut voor Biotechnologie (VIB) and FWO.

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HR and BS conceived the project, TB, JP, and BS designed and conducted the simulations. TB designed and conducted the experiments. TB and BS performed data analysis. TB, HS, and BS wrote the manuscript. All authors commented on the manuscript.

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Correspondence to Tom E. R. Belpaire.

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Belpaire, T.E.R., Pešek, J., Lories, B. et al. Permissive aggregative group formation favors coexistence between cooperators and defectors in yeast. ISME J (2022). https://doi.org/10.1038/s41396-022-01275-y

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