Evolution of molecular communication in the permanent Azolla symbiosis

Heritable symbioses exist across eukaryotes with different degrees of intimacy. In most cases, the symbionts are obligate and require inheritance for their survival. On the host side, symbiont retention can facilitate fitness benefits. Only rarely are these symbioses interwoven to the point that host survival relies on the symbiont. In land plants, the symbiosis of the water fern Azolla with its symbiotic cyanobacterium shows such a degree of high co-dependence. The symbiosis originated in the last common ancestor of Azolla and exists continuously for at least 60 million years with no evolutionarily stable, secondary loss of the symbiont reported. This is a feat achieved by interactions on an organellar-like level or those considered recent organelle acquisitions. Yet, Azolla's symbiont is extracellular. How can loss of autonomy concomitant with full co-dependence be accommodated in this extracellular symbiosis? Here, we synthesize what we know from the Azolla symbiosis on the consequences of evolutionary co-dependence and stable symbiont retention. We discuss the need for symbiotic integration into environmental responsiveness if host survival depends on symbiont well-being. Cross-organismal integration of environmental stress responses may be one of the key steps that favor this evolutionarily stable permanent integration.