Archaeal Genes Code for GGDEF Domain Proteins With Diguanylate Cyclase Activity

ABSTRACT Cyclic di‐GMP is ubiquitous in Bacteria, including members of the deepest branching phyla, but has not yet been detected in Archaea. Thus, whether cyclic di‐GMP was present as a signaling nucleotide in the last universal common ancestor (LUCA) of Bacteria and Archaea remains unknown. In this work, bioinformatic analyses and structural modelling identified GGDEF domain proteins in archaeal isolates and encoded by metagenomes of confirmed archaeal origin. In particular, in bacterial model organisms, phenotypic and in vivo assays, in combination with catalytic mutants, suggest that selected archaeal GGDEF domain proteins possess diguanylate cyclase activity. These include the complex REC S ‐PAS/PAC‐PocR‐GGDEF‐HD‐GYP domain protein of Methanocella arvoryzae MRE50, a member of the Stenosarchaea order Methanocellales . While cyclic di‐GMP signaling proteins are ubiquitous in Bacteria, their presence seems to be more sporadic in Archaea. It is currently unclear whether cyclic di‐GMP signaling proteins have been lost in some lineages, secondarily introduced by horizontal gene transfer into others, or whether both scenarios have occurred.