# A Genomic Survey of Signalling in the Myxococcaceae
## 1 Introduction
Due to their abundance, and the wealth of knowledge regarding their functioning, we particularly wanted to assess the patterns of conservation of myxobacterial signalling genes, to better understand which pathways and processes regulate core myxobacterial functions and which are unique to individual species or strains. We therefore investigated three exemplar myxobacterial signalling pathways: carotenogenesis, fruiting body development and quorum signalling. Production of photo-protective carotenoid pigments is regulated by illumination in _M. xanthus_ via the Car pathway. Exposure to light stimulates release of the alternative sigma factor CarQ, to direct transcription of _carS_[12; 13; 14]. CarS is an anti-repressor of the _crt_ carotenoid biosynthetic genes [15; 16; 17]. The pathway is essentially a long linear signalling pathway, supplemented by a second repressor, which is directly inactivated by light [18]. When a population of myxobacteria is starved, it produces a multicellular fruiting body containing myxospores [19; 20; 21; 22]. The regulators of fruiting body formation are dominated by TCS proteins, organised into largely discrete modules. Development requires the integration of signals from multiple modules, with the secondary messengers c-di-GMP (cyclic di-GMP) and (p)ppGpp, and two major intercellular signals: A-signal is a quorum signal, while C-signalling is a consequence of cell-cell contact [22; 23]. Quorum signalling (QS) pathways are simple, and multiple independent pathways can be found in some organisms [24; 25]. A synthase enzyme makes the QS signal (or autoinducer, AI), which is then typically transduced by either a DNA-binding transcription factor or a TCS pathway. Typical AIs include AI-I, AI-II, CAI-I and HAI-I (autoinducer-1, autoinducer-2, cholerae autoinducer-1 and harveyi autoinducer-1) [24; 25]. Myxobacteria are not known to produce any AIs, however they have recently been shown to modulate myxobacterial behaviour [26]. The signalling pathways underpinning carotenoid production, fruiting body formation and QS are therefore very different, both in organisation and in the type of regulators involved, and we hypothesised that the pathway regulators would exhibit different patterns of conservation as a consequence. To that end, we surveyed the signalling proteins found in the genomes of four distinct groups of Myxococcaceae--the ten type strains of _Corallococcus_ spp., the eleven type strains of _Myxococcus_Psxidicoccus_ spp., ten strains of _M. xanthus_ and ten strains of _Corallococcus exigus_ (including four genomes described here for the first time). Our analysis included TCS, Ser/Thr kinases, sigma factors, OCS and other TRs. We did not include regulatory ncRNAs (non-coding RNAs) as they have been recently surveyed elsewhere [27]. Despite their large numbers, signalling proteins (particularly TCS proteins) were found to be enriched in the core Myxococcaceaeal genome. While the linear carotenogenesis pathway was wholly conserved, the conservation of components of the fruiting body network was highly variable. The Myxococcaceae also generally appear to be able to produce QS signals, and to sense/disrupt the QS of other organisms.