Prediction of protein architectures involved in the signaling-pathway initiating sporulation in Firmicutes
Like many other proteins, those belonging to the signal transduction cascade initiating sporulation (Spo0 pathway) have conserved protein domains (Capra and Laub in Annu Rev Microbiol 66:325–47, 2012). Improvements in bioinformatics applications to discover proteins involved in the initiation of the sporulating cascade in newly sequenced genomes is an important task that requires rigorous comparative genomic methods and manual curation to identify endospore-forming bacteria. This note aims to present a collection of predicted proteins involved in the Spo0 pathway found in the proteomes of fully sequenced and manually curated endospore-forming Firmicutes species. This collection may serve as a guide to conduct future experiments in endospore formers in genomic and metagenomic projects.
Similar to the report of Davidson et al. (PLoS Genet 14:1–33, 2018), we used Pfam profiles (El-Gebali et al. in Nucleic Acids Res 47:D427–32, 2019) defining each protein and the genomic context surrounding the query gene to predict probable orthologs of the Spo0 pathway in Firmicutes. We present in this note a collection of 325 Firmicutes species organized by phylogenetic class and classified as spore formers, non-spore formers or unknown spore phenotype based on published literature, for which we predicted probable orthologs defining the signal transduction pathway initiating sporulation.
KeywordsSporulation Firmicutes Protein architecture Orthologs
hidden Markov model
cluster of orthologous genes
Comparative genomic analysis is a valuable tool to explore new genomes and metagenomes to search for functional processes, phylogenetic relationships, and evolutionary traits among organisms. An example of this comparative analysis is finding that proteins involved in the Spo0 pathway constitute of at least a sensor kinase, the phosphotransferases Spo0F and Spo0B, and the response regulator Spo0A , were suggested to be ancestral since it was found not only in Bacilli but also in some Clostridia . While an original article from our group that describes the distribution and prevalence of the Spo0 pathway and also confirms that this pathway is ancestral was under review, the results mentioned above were published by Davidson and collaborators using a set 84 Firmicutes . Therefore, in this note, we provide a more extensive list of manually curated Firmicutes possessing different forms of the Spo0 pathway initiating sporulation in Firmicutes.
Overview of data files/data sets
Name of data file/data set
File type (file extension)
Data repository and identifier (DOI or accession number)
Data File 1 
Architectures, Pfams and model organisms
MS Excel file (.xlsx)
Figshare ( https://doi.org/10.6084/m9.figshare.9701522)
Data File 2 
MS Excel file (.xlsx)
Figshare ( https://doi.org/10.6084/m9.figshare.9701630)
Data File 3 
Spo0 predicted pathways and curated Firmicutes
MS Excel file (.xlsx)
Figshare ( https://doi.org/10.6084/m9.figshare.9876683)
To detect orphan histidine kinases (HKo), defined as kinases not having as a neighboring response regulator , we performed a hmmscan using the profiles of the PfamA shown in Table 1, Data File 1  and kept those hits with an expectation value > 0.001 that fulfill the architectures described in Table 1, Data File 1 . As an additional condition, we discarded those sequences that did not have the same number of domains and with a length no more than twice the length of the model. As the architectures were constructed using proteins experimentally proven to participate in sporulation (Table 1, Data File 1) , we considered for this analysis the architecture found in Clostridium thermocellum, which is composed of a HisKA, an HATPase, and a response regulator domain (Table 1, Data File 1) .
Spo0 pathways found for each endospore former are shown in Table 1, Data File 3 . These results show the architectures describing twelve HKos, three architectures representing transferases, and two architectures describing the response regulator Spo0A. The final table includes 185 Bacilli, 134 Clostridia, 4 Negativicutes, and 2 Erysipelotrichia species.
Experimental evidence of a sporulation phenotype is not available for a vast number of strains since the conditions have not been identified.
New protein profiles should be constructed to identify novel orphan kinases.
A study should be performed in newly sequenced genomes to increase the collection; nonetheless, the groups presented in this note are probably enough to confirm the main conclusions found by both groups.
We thank Ricardo Ciria, Walter Santos, Juan Manuel Hurtado, David Santiago Castañeda Carreón, and Shirley Ainsworth for their technical and bibliographical support.
All data and materials described herein are available in the links provided in the main text.
PMA was responsible for data preparation and method development. AL was responsible for data preparation. LS and NGC were responsible for manual curation. EM was responsible for COG identification. RMGR was involved in data preparation, method improvement, data analysis, and manual curation and wrote the manuscript. PMA, LS, NC, AL, EM, and RMGR reviewed the manuscript. All authors read and approved the final manuscript.
The design of the study and data collection was supported by the grant IN202118 from PAPIIT-UNAM awarded to RMGR. A CONACyT scholarship supported Paola Martinez-Amador, Lizeth Soto-Avila, and Nori Castañeda-Gomez. Antonio Loza was supported by a postdoctoral scholarship of the Consorcio de Investigación del Golfo de México (CIGoM), which is supported by the National Council of Science and Technology of Mexico—Mexican Ministry of Energy—Hydrocarbon Trust, project 201441.
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Consent for publication
The author declares that she has no competing interests.
The authors declare that they have no competing interests.
- 3.Data file 1. Proteins model architectures of the signal transduction cascade in endospore formers. 2019. https://doi.org/10.6084/m9.figshare.9701522.
- 7.KEGG Organisms: complete genomes. https://www.genome.jp/kegg/catalog/org_list.html.
- 12.Data file 2. COG defining the Spo0 pathway. 2019. https://doi.org/10.6084/m9.figshare.9701630.
- 14.Data file 3. Spo0 pathwaySpo0 predicted pathways and curated Firmicutes. 2019. https://doi.org/10.6084/m9.figshare.9876683.
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