Functional dissection of the CRP-family transcription factor DevH and its interplay with NtcA in a cyanobacterium

Gene duplication and subsequent functional diversification of transcription factors represent a fundamental evolutionary strategy for microbial adaptation. In Anabaena PCC 7120, NtcA and DevH, both belonging to the CRP-family transcription factors, share extensive overlapping functions but show distinct regulatory roles. Both of them play critical functions, particularly in heterocyst development and cell survival under various conditions. Then, how do they achieve functional diversification? Since devH is essential, we used a conditional devH mutant to define the DevH regulon and identified its consensus DNA-binding motif. Comparative analyses of their protein levels, DNA-binding properties, and structural features showed that DevH, unlike NtcA, operates at higher cellular concentrations and exhibits broader regulatory functions independent of allosteric control. Phylogenomic studies further support the evolutionary specialization of these paralogs. Our findings illustrate how duplicated transcription factors enhance regulatory complexity, optimizing cyanobacterial fitness in dynamically changing environments.