Functional diversification of the MADS-box gene family in fine-tuning the dimorphic transition of Talaromyces marneffei

The dynamic transition between yeast and hypha is a crucial adaptive mechanism for many human pathogenic fungi, including Talaromyces marneffei, a thermodimorphic fungus responsible for causing fatal talaromycosis. In the current study, we elucidated the roles of the MADS-box gene family in fine-tuning the dimorphic transition in T. marneffei through functional diversification. Utilizing adaptive laboratory evolution, we identified an enrichment of MADS-box genes in mutants deficient in yeast-to- mycelium transition. Further phylogenetic analyses revealed a significant expansion of MADS-box gene family within T. marneffei. Functional genetic manipulations revealed that overexpression of mads9, as opposed to its paralog mads10, effectively impeded the hyphal-to-yeast transition. Through integrating RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq), we demonstrated that mads9 and the previously characterized madsA modulated the rate of hyphal-to-yeast conversion by orchestrating metabolic pathways and membrane dynamics, respectively, with mutual regulation via shared target genes. Our findings illuminated the distinct functional roles of the MADS-box family in regulating dimorphic transitions in T. marneffei, offering new insights into fungal adaptability.