hetR and patS, two genes necessary for heterocyst pattern formation, are widespread in filamentous non heterocyst-forming cyanobacteria

Heterocysts, cells specialized in N-2 fixation in cyanobacteria, appeared at near to 2.1 Ga. They constitute one of the oldest forms of differentiated cells in evolution, and are thus an interesting model for studies on evolutionary-developmental biology. How heterocysts arose during evolution remains unknown. In Anabaena PCC 7120, heterocyst development requires, among other genes, hetR for the initiation of heterocyst differentiation, and patS, encoding a diffusible inhibitor of heterocyst formation. In this study, we report that both hetR and patS are widespread among filamentous cyanobacteria that do not form heterocysts or fix N-2. hetR and patS are found in proximity on the chromosome in several cases, such as Arthrospira platensis, in which the level of HetR increased following nitrogen deprivation. The hetR gene of A. platensis could complement a hetR mutant of Anabaena PCC 7120, and patS of A. platensis could suppress heterocyst differentiation in Anabaena PCC 7120. Thus, key regulatory genes, including hetR and patS, involved in heterocyst development may have evolved before heterocysts appeared, suggesting that their function was not limited to heterocyst differentiation.