When growth becomes risky: stress-driven sporulation and sexual development in fungi

Abstract

Fungi frequently encounter nutrient limitation, osmotic stress, oxidative pressure, light fluctuations, temperature shifts, and host-associated stresses. Rather than responding passively to deteriorating environments, many fungi actively redirect development from vegetative growth toward asexual sporulation, sexual reproduction, or resting structure formation. These transitions promote dispersal, dormancy, stress resistance, or genetic diversification, but they are not governed by a single conserved stress-response pathway. Instead, conserved nutrient- and stress-sensing modules are integrated with lineage-specific developmental circuits. This review synthesizes recent advances in understanding how environmental stress, particularly nutrient limitation, regulates fungal reproductive development. We discuss nutrient limitation as both a physiological constraint and a developmental signal, and compare regulatory mechanisms across yeasts, filamentous ascomycetes, and pathogenic fungi. Major pathways and regulatory layers include cAMP-PKA, TOR, HOG MAPK signaling, light-responsive systems, the Velvet complex, chromatin regulation, diffusible chemical signals, and sexual-stage-specific adenosine-to-inosine (A-to-I) mRNA editing. Together, these mechanisms determine whether fungi remain vegetative or commit to reproduction. We also evaluate why sexual reproduction may be favored under stressful or low-fitness conditions. While asexual spores and resting structures can enhance survival and dispersal, costly meiotic reproduction may be promoted when recombination allows offspring or alleles to escape maladapted genetic backgrounds. Fitness-associated sex and abandon-ship models therefore provide useful evolutionary frameworks for interpreting stress-induced reproduction. Understanding these mechanisms is timely and important because fungal reproductive switching affects industrial spore production, pathogen transmission, disease management, and evolutionary potential. Future progress will require causal, ecologically grounded models linking environmental perception, molecular regulation, reproductive output, and fitness consequences.

Keywords

Fungal development / Sporulation / Sexual reproduction / Nutrient limitation / Stress signaling / RNA editing / Disease management

References

[1] Adams TH, Wieser JK, Yu JH. Asexual sporulation in Aspergillus nidulans. Microbiol Mol Biol Rev, 1998, 62(1): 35-54

[2] Atanasoff-Kardjalieff AK, Studt L. Secondary metabolite gene regulation in mycotoxigenic Fusarium species: a focus on chromatin. Toxins (Basel), 2022, 14(2): 96

[3] Baker CL, Loros JJ, Dunlap JC. The circadian clock of Neurospora crassa. FEMS Microbiol Rev, 2012, 36(1): 95-110

[4] Bayram Ö, Braus GH. Coordination of secondary metabolism and development in fungi: The velvet familyof regulatory proteins. FEMS Microbiol Rev, 2012, 36(1): 1-24

[5] Bayram Ö, Krappmann S, Ni M, Bok JW, Helmstaedt K, Valerius O, Braus-Stromeyer S, Kwon N-J, Keller NP, Yu J-H, Braus GH. VelB/VeA/LaeA complex coordinates light signal with fungal development and secondary metabolism. Science, 2008, 320(5882): 1504-1506

[6] Bian ZY, Ni YJ, Xu JR, Liu HQ. A-to-I mRNA editing in fungi: occurrence, function, and evolution. Cell Mol Life Sci, 2019, 76(2): 329-340

[7] Calvo AM. The VeA regulatory system and its role in morphological and chemical development in fungi. Fungal Genet Biol, 2008, 45(7): 1053-1061

[8] Chen H, Fink GR. Feedback control of morphogenesis in fungi by aromatic alcohols. Genes Dev, 2006, 20(9): 1150-1161

[9] Collemare J, Seidl MF. Chromatin-dependent regulation of secondary metabolite biosynthesis in fungi: is the picture complete?. FEMS Microbiol Rev, 2019, 43(6): 591-607

[10] Dijksterhuis J (2019) Fungal spores: Highly variable and stress-resistant vehicles for distribution and spoilage. Food Microbiol 81:2–11. https://doi.org/10.1016/j.fm.2018.11.006

[11] Du YF, Wang CH, Zhang Y, Liu HQ. Evolutionary origins and adaptive significance of A-to-I RNA editing in animals and fungi. BioEssays, 2025, 47(5 ArticleID: e202400220

[12] Du YF, Zhang Y, Wang CH, Huang Y, Wu MC, Huang JQ, Hou MD, Wang QH, Jiang C, Liu HQ. Beyond gene duplication: A-to-I RNA editing-mediated stop codon readthrough modulates Dbf2 dosage to resolve pleiotropic conflicts. Proc Natl Acad Sci U S A, 2026, 123(17 ArticleID: e2532534123

[13] Dunlap JC, Loros JJ. The Neurospora circadian system. J Biol Rhythms, 2004, 19(5): 414-424

[14] Engh I, Nowrousian M, Kück U. Sordaria macrospora, a model organism to study fungal cellular development. Eur J Cell Biol, 2010, 89(12): 864-872

[15] Feng CJ, Xin KY, Du YF, Zou JW, Xing XX, Xiu Q, Zhang YJ, Zhang R, Huang WW, Wang QH, Jiang C, Wang XJ, Kang ZS, Xu JR, Liu H. Unveiling the A-to-I mRNA editing machinery and its regulation and evolution in fungi. Nat Commun, 2024, 15 ArticleID: 3934

[16] Gacek A, Strauss J. The chromatin code of fungal secondary metabolite gene clusters. Appl Microbiol Biotechnol, 2012, 95(6): 1389-1404

[17] Gao L, Liu X. Nutritional requirements of mycelial growth and sporulation of several biocontrol fungi in submerged and on solid culture. Microbiol, 2010, 79(5): 612-619

[18] Garrido-Bazán V, Jaimes-Arroyo R, Sánchez O, Lara-Rojas F, Aguirre J. SakA and MpkC stress MAPKs show opposite and common functions during stress responses and development in Aspergillus nidulans. Front Microbiol, 2018, 9 ArticleID: 2518

[19] Gerber N, Kokko H. Abandoning the ship using sex, dispersal or dormancy: multiple escape routes from challenging conditions. Philos Trans R Soc B Biol Sci, 2018

[20] Guan G, Tao L, Li C, Xu M, Liu L, Bennett RJ, Huang G. Glucose depletion enables Candida albicans mating independently of the epigenetic white-opaque switch. Nat Commun, 2023, 14(1 ArticleID: 2067

[21] Hadany L, Beker T. On the evolutionary advantage of fitness-associated recombination. Genetics, 2003, 165(4): 2167-2179

[22] Hadany L, Otto SP. Condition‐dependent sex and the rate of adaptation. Am Nat, 2009, 174(S1): S71-S78

[23] Hohmann S. Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev, 2002, 66(2): 300-372

[24] Honigberg SM, Purnapatre K. Signal pathway integration in the switch from the mitotic cell cycle to meiosis in yeast. J Cell Sci, 2003, 116(11): 2137-2147

[25] Jiang J, Yun Y, Liu Y, Ma Z. FgVELB is associated with vegetative differentiation, secondary metabolism and virulence in Fusarium graminearum. Fungal Genet Biol, 2012, 49(8): 653-662

[26] Jiang ST, Chang AN, Han LT, Guo JS, Li YH, Liu TB. Autophagy regulates fungal virulence and sexual reproduction in Cryptococcus neoformans. Front Cell Dev Biol, 2020, 8: 374

[27] Kato N, Brooks W, Calvo AM. The expression of sterigmatocystin and penicillin genes in Aspergillus nidulans is controlled by veA, a gene required for sexual development. Eukaryot Cell, 2003, 2(6): 1178-1186

[28] Keller NP, Turner G, Bennett JW. Fungal secondary metabolism—from biochemistry to genomics. Nat Rev Microbiol, 2005, 3(12): 937-947

[29] Kim JY, Bahn YS. Role of the heme activator protein complex in the sexual development of Cryptococcus neoformans. mSphere, 2022, 7(3 ArticleID: e00170-22

[30] Kim H, Kim HK, Lee S, Yun SH. The White Collar complex is involved in sexual development of Fusarium graminearum. PLoS ONE, 2015, 10(3 ArticleID: e0120293

[31] Lara-Rojas F, Sánchez O, Kawasaki L, Aguirre J. Aspergillus nidulans transcription factor AtfA interacts with the MAPK SakA to regulate general stress responses, development and spore functions. Mol Microbiol, 2011, 80(2): 436-454

[32] Lengeler KB, Davidson RC, D’souza C, Harashima T, Shen WC, Wang P, Pan X, Waugh M, Heitman J. Signal transduction cascades regulating fungal development and virulence. Microbiol Mol Biol Rev, 2000, 64(4): 746-785

[33] Liu HQ, Wang QH, He Y, Chen LF, Hao CF, Jiang C, Li Y, Dai YF, Kang ZS, Xu JR. Genome-wide A-to-I RNA editing in fungi independent of ADAR enzymes. Genome Res, 2016, 26(4): 499-509

[34] Liu HQ, Li Y, Chen DP, Qi ZM, Wang QH, Wang JH, Jiang C, Xu JR. A-to-I RNA editing is developmentally regulated and generally adaptive for sexual reproduction in Neurospora crassa. Proc Natl Acad Sci U S A, 2017, 114(37): E7756-E7765

[35] Loewith R, Hall MN. Target of Rapamycin (TOR) in nutrient signaling and growth control. Genetics, 2011, 189(4): 1177-1201

[36] Mata J, Lyne R, Burns G, Bähler J. The transcriptional program of meiosis and sporulation in fission yeast. Nat Genet, 2002, 32(1): 143-147

[37] Miller MG, Johnson AD. White-opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Cell, 2002, 110(3): 293-302

[38] Neiman AM. Ascospore formation in the yeast Saccharomyces cerevisiae. Microbiol Mol Biol Rev, 2005, 69(4): 565-584

[39] Niu M, Steffan BN, Fischer GJ, Venkatesh N, Raffa NL, Wettstein MA, Bok JW, Greco C, Zhao C, Berthier E, Oliw E, Beebe D, Bromley M, Keller NP. Fungal oxylipins direct programmed developmental switches in filamentous fungi. Nat Commun, 2020, 11(1): 5158

[40] Nowrousian M. The role of chromatin and transcriptional control in the formation of sexual fruiting bodies in fungi. Microbiol Mol Biol Rev, 2022, 86(4): e00104-e122

[41] Osborne LE, Stein JM. Epidemiology of Fusarium head blight on small-grain cereals. Int J Food Microbiol, 2007, 119(1–2): 103-108

[42] Otsubo Y, Yamamoto M. Signaling pathways for fission yeast sexual differentiation at a glance. J Cell Sci, 2012, 125(12): 2789-2793

[43] Park HS, Yu JH. Genetic control of asexual sporulation in filamentous fungi. Curr Opin Microbiol, 2012, 15(6): 669-677

[44] Pfannenstiel BT, Keller NP. On top of biosynthetic gene clusters: how epigenetic machinery influences secondary metabolism in fungi. Biotechnol Adv, 2019, 37(6 ArticleID: 107345

[45] Pöggeler S, Nowrousian M, Teichert I, Beier A, Kück UAnke T, Schüffler A. Fruiting-body development in Ascomycetes. Physiology and genetics: selected basic and applied aspects, 2018Springer International Publishing1-56

[46] Qi ZM, Lu P, Long XY, Cao XY, Wu MC, Xin KY, Xue T, Gao XL, Huang Y, Wang QH, Jiang C, Xu JR, Liu HQ. Adaptive advantages of restorative RNA editing in fungi for resolving survival-reproduction trade-offs. Sci Adv, 2024, 10(1 ArticleID: eadk6130

[47] Saito H. Regulation of the osmoregulatory HOG MAPK cascade in yeast. J Biochem, 2004, 136(3): 267-272

[48] Schoustra S, Rundle HD, Dali R, Kassen R. Fitness-associated sexual reproduction in a filamentous fungus. Curr Biol, 2010, 20(15): 1350-1355

[49] Schumacher JFillinger S, Elad Y. Signal transduction cascades regulating differentiation and virulence in Botrytis cinerea. Botrytis – the fungus, the pathogen and its management in agricultural systems, 2016Springer International Publishing247267

[50] Seudre O, Namias A, Gardella O, Da Silva G, Gouyon PH, López-Villavicencio M. Why outcross? The abandon-ship hypothesis in a facultative outcrossing/selfing fungal species. Fungal Genet Biol, 2018, 120: 1-8

[51] Silar PHorwitz BA, Mukherjee PK, Mukherjee M, Kubicek CP. Podospora anserina : from laboratory to biotechnology. Genomics of soil- and plant-associated fungi, 2013Springer Berlin Heidelberg283309 36

[52] Strauss J, Reyes-Dominguez Y. Regulation of secondary metabolism by chromatin structure and epigenetic codes. Fungal Genet Biol, 2011, 48(1): 62-69

[53] Talbot NJ. On the trail of a cereal killer: exploring the biology of Magnaporthe grisea. Annu Rev Microbiol, 2003, 57(1): 177-202

[54] Trail F. For blighted waves of grain: Fusarium graminearum in the postgenomics era. Plant Physiol, 2009, 149(1): 103-110

[55] Tsitsigiannis DI, Keller NP. Oxylipins as developmental and host–fungal communication signals. Trends Microbiol, 2007, 15(3): 109-118

[56] Tsuyuzaki H, Hosokawa M, Arikawa K, Yoda T, Okada N, Takeyama H, Sato M. Time-lapse single-cell transcriptomics reveals modulation of histone H3 for dormancy breaking in fission yeast. Nat Commun, 2020, 11(1 ArticleID: 1265

[57] Van Werven FJ, Amon A (2011) Regulation of entry into gametogenesis. Philos Trans R Soc Lond B Biol Sci 366(1584):3521–3531. https://doi.org/10.1098/rstb.2011.0081

[58] Veneault-Fourrey C, Barooah M, Egan M, Wakley G, Talbot NJ. Autophagic fungal cell death is necessary for infection by the rice blast fungus. Science, 2006, 312(5773): 580-583

[59] Wang CF, Xu JR, Liu HQ. A-to-I RNA editing independent of ADARs in filamentous fungi. RNA Biol, 2016, 13(10): 940-945

[60] Wang F, Sethiya P, Hu X, Guo S, Chen Y, Li A, Tan K, Wong KH. Transcription in fungal conidia before dormancy produces phenotypically variable conidia that maximize survival in different environments. Nat Microbiol, 2021, 6(8): 1066-1081

[61] Wang Y, Zheng X, Li G, Wang X. TORC1 signaling in fungi: From yeasts to filamentous fungi. Microorganisms, 2023, 11(1): 218

[62] Willetts HJ. The survival of fungal sclerotia under adverse environmental conditions. Biol Rev, 1971, 46(3): 387-407

[63] Wu MC, Liu JF, Cao PN, Liu MQ, Feng CJ, Wang QH, Jiang C, Xu JR, Liu HQ. Epitranscriptomic RNA editing resolves Mus81 DNA repair tradeoffs in heat tolerance and meiosis. Nat Commun, 2026, 17(1): 4617

[64] Wu MC, Liu JF, Han JH, Huang JQ, Feng CJ, Jiang C, Xu JR, Wang QH, Liu HQ. Adaptive Spo11 RNA editing gate optimizes meiosis I pace and mitotic proliferation while preserving ascospore formation. Sci Adv, 2026, 12(24 ArticleID: eadu7607

[65] Wyatt TT, Wösten HAB, Dijksterhuis J (2013) Fungal spores for dispersion in space and time. Adv Appl Microbiol 85:43–91. https://doi.org/10.1016/B978-0-12-407672-3.00002-2

[66] Xin KY, Zhang Y, Fan LG, Qi ZM, Feng CJ, Wang QH, Jiang C, Xu JR, Liu HQ. Experimental evidence for the functional importance and adaptive advantage of A-to-I RNA editing in fungi. Proc Natl Acad Sci U S A, 2023, 120(12 ArticleID: e2219029120

[67] Xin KY, Kang XB, Liu MQ, Fan JJ, Du YF, Feng CJ, Liu HQ. Navigating trade-offs: the adaptive significance of A-to-I RNA editing in fungi, bacteria, and animals. Epigenet Insights, 2025

[68] Yamamoto M. The molecular control mechanisms of meiosis in fission yeast. Trends Biochem Sci, 1996, 21(1): 18-22

[69] Yamamoto M. The selective elimination of messenger RNA underlies the mitosis-meiosis switch in fission yeast. Proc Jpn Acad B, 2010, 86(8): 788-797

[70] Yu F, Gu Q, Yun Y, Yin Y, Xu JR, Shim WB, Ma Z. The TOR signaling pathway regulates vegetative development and virulence in Fusarium graminearum. New Phytol, 2014, 203: 219-232

[71] Zheng Q, Guan G, Cao C, Li Q, Huang G. The PHO pathway regulates white–opaque switching and sexual mating in the human fungal pathogen Candida albicans. Curr Genet, 2020, 66(6): 1155-1162

RIGHTS & PERMISSIONS

The Author(s)