Ancient sex compatibility genes underlie tissue differentiation in mushrooms

Complex multicellular development through tissue differentiation and organogenesis is among the most complex, but least understood genetic mechanisms of living systems. Development across different organisms converges on a miniature blueprint of the mature organism, which, in animals, plants and brown algae, is mostly achieved via embryogenesis, resulting in distinct tissues and organs1,2. Fungal fruiting bodies are complex multicellular structures, but in contrast to other organisms, they are assembled via apical growth of tubular hyphae3, a unique mechanism for the fungal kingdom. How hyphal growth was adapted to enable complex development, whether regions of the fruiting body function as real tissues and what are the key regulators of differentiation - equivalents of Hox genes of animals or ABC genes of plants - have remained unknown. Here we show that fruiting bodies of mushroom-forming fungi evolved hallmarks of bona fide tissues, such as distinct transcriptomic footprints, functions, and specialization and we uncover tissue-specific transcriptome patterns and genetic networks underlying their development. We discover that mating pheromones and their receptors, as well as a gene family required for pheromone maturation, are required for tissue differentiation and form distinct, tissue-specific pathways driving differentiation. Ancestrally, these genes regulate mating behaviour, indicating co-option during evolution and that Agaricomycetes use the same genetic system to control sexual compatibility and tissue development. This study uncovers how evolution produced complex tissues from apically growing hyphae, and illustrates that selection can drive the convergent evolution of tissues across organisms with fundamentally different cellular architectures.