Tuesday, 15 April 2025
File under "well said" CXVI
"It does not matter how far ahead you can see if you don't understand what you are looking at"
Gary kasparov
Independently recurring design logic vs. Darwin.
Sporulation: Another Example of a Transcriptional Hierarchy
Previously, I introduced the subject of transcriptional hierarchies in bacteria, which exhibit current design logic across various different systems. We reviewed the control of flagellar assembly in Salmonella and saw that the organization of flagellar genes along the chromosome, and their organization into different operons (collections of genes under control of a common promoter), is crucial to the assembly process. Here, I will discuss another example of a transcriptional hierarchy — the control of sporulation
What Is Sporulation?
Sporulation is a highly regulated process whereby a vegetative cell differentiates into an endospore, a highly resistant, dormant structure that can withstand extreme stress (such as heat, desiccation, and UV radiation). The process is triggered by nutrient starvation. Once sporulation has been initiated, the chromosomes align along the longitudinal axis of the cell — this is known as the axial filament.1 The cell then divides asymmetrically near one of the poles, forming the smaller forespore and the larger mother cell.2,3 The membrane of the mother cell subsequently engulfs the forespore such that it completely envelops it.4 A thick layer of peptidoglycan (known as the cortex) is then deposited between the forespore membranes (this Is crucial for dehydration and dormancy).5 Physical and chemical resistance is conferred by proteinaceous layers known as spore coats, which assemble around the cortex.6 Eventually the mother cell undergoes apoptosis, which releases the mature spore.7
The model system for studying sporulation is Bacillus subtilis (pictured at the top), which I will be focusing on here.
Regulation of Endospore Formation
Similar to flagellar assembly, which we considered previously, sporulation is under the control of a transcriptional hierarchy, whereby sigma factors promote the expression of specific sets of genes.8
The master regulator of sporulation is Spo0A, which is activated by phosphorylation in response to stress, via a phosphorelay system.9,10 Environmental stress signals are detected by sensor histidine kinases (KinA, KinB, and KinC), which in response undergo autophosphorylation.11 The response regulator for this system is Spo0F, which receives the phosphate group from the histidine kinases. This phosphate group, in turn, is transferred to Spo0A by the phosphotransferase Spo0B. This represents a further example of the recurring design logic exhibited by two-component regulatory systems, which I discussed in a previous article.
Phosphorylated Spo0A deactivates abrB, a repressor of early sporulation genes.12 This facilitates expression of spoIIE, which encodes a phosphatase that dephosphorylates SpoIIAA, which otherwise binds and inhibits SpoIIAB (a protein which inactivates σF).13 σF is thereby released and promotes the transcription of a regulon (i.e., a collection of multiple operons that are transcribed in response to the same regulatory protein).14 These genes are primarily involved in the early stages of endospore formulation — in particular, in the forespore compartment.
Among the genes that are under the regulation of σF is a gene coding for a signaling protein called SpoIIR, which activates SpoIIGA, a protease that cleaves pro-σE into its active form, σE.15 σE, in turn, drives the expression of the genes needed for modification of the mother cell membrane to envelop the forespore.16 σE also drives expression of SpoIVB, which cleaves SpoIVFA, a protein which, along with another molecule called BofA, inhibits a membrane-associated protease called SpoIVFB.17,18 This cleavage releases the inhibitory complex, thereby rendering SpoIVB active. This protease, along with another protein called CtpB, cleaves pro-σK, converting it to active σK.19,20 This, in turn, directs the transcription of the genes that code for coat proteins and lytic enzymes that bring about the death of the mother cell.21
Recurring Design Logic
In my previous article, I surveyed the transcriptional hierarchy responsible for the assembly of bacterial flagella. We saw that the organization of genes into operons relates to the timing of their expression — in particular, whether they are expressed early, midway, or late in flagellar assembly. In the foregoing, we have seen a very similar design logic exhibited by the transcriptional hierarchy that is sporulation. And yet, nobody would argue that these systems are evolutionarily related to one another. Recurring design logic across multiple unrelated systems is surprising in an evolutionary perspective, whereas on the hypothesis of design it is what might be reasonably predicted. Examples like this, therefore, suggest the existence of a master-architect behind biological systems — particularly when we find many different examples of design logic that are found recurrently throughout life.
Notes
Bylund JE, Haines MA, Piggot PJ, Higgins ML. Axial filament formation in Bacillus subtilis: induction of nucleoids of increasing length after addition of chloramphenicol to exponential-phase cultures approaching stationary phase. J Bacteriol. 1993 Apr;175(7):1886-90. doi: 10.1128/jb.175.7.1886-1890.1993. PMID: 7681431; PMCID: PMC204252.
Barák I, Muchová K, Labajová N. Asymmetric cell division during Bacillus subtilis sporulation. Future Microbiol. 2019 Mar;14:353-363. doi: 10.2217/fmb-2018-0338. Epub 2019 Mar 11. PMID: 30855188.
Khanna K, Lopez-Garrido J, Sugie J, Pogliano K, Villa E. Asymmetric localization of the cell division machinery during Bacillus subtilis sporulation. Elife. 2021 May 21;10:e62204. doi: 10.7554/eLife.62204. PMID: 34018921; PMCID: PMC8192124.
Ojkic N, López-Garrido J, Pogliano K, Endres RG. Cell-wall remodeling drives engulfment during Bacillus subtilis sporulation. Elife. 2016 Nov 17;5:e18657. doi: 10.7554/eLife.18657. PMID: 27852437; PMCID: PMC5158138.
Popham DL, Bernhards CB. Spore Peptidoglycan. Microbiol Spectr. 2015 Dec;3(6). doi: 10.1128/microbiolspec.TBS-0005-2012. PMID: 27337277.
McKenney PT, Driks A, Eichenberger P. The Bacillus subtilis endospore: assembly and functions of the multilayered coat. Nat Rev Microbiol. 2013 Jan;11(1):33-44. doi: 10.1038/nrmicro2921. Epub 2012 Dec 3. PMID: 23202530; PMCID: PMC9910062.
Hosoya S, Lu Z, Ozaki Y, Takeuchi M, Sato T. Cytological analysis of the mother cell death process during sporulation in Bacillus subtilis. J Bacteriol. 2007 Mar;189(6):2561-5. doi: 10.1128/JB.01738-06. Epub 2007 Jan 5. PMID: 17209033; PMCID: PMC1899390.
Eichenberger P, Fujita M, Jensen ST, Conlon EM, Rudner DZ, Wang ST, Ferguson C, Haga K, Sato T, Liu JS, Losick R. The program of gene transcription for a single differentiating cell type during sporulation in Bacillus subtilis. PLoS Biol. 2004 Oct;2(10):e328. doi: 10.1371/journal.pbio.0020328. Epub 2004 Sep 21. PMID: 15383836; PMCID: PMC517825.
Chastanet A, Losick R. Just-in-time control of Spo0A synthesis in Bacillus subtilis by multiple regulatory mechanisms. J Bacteriol. 2011 Nov;193(22):6366-74. doi: 10.1128/JB.06057-11. Epub 2011 Sep 23. PMID: 21949067; PMCID: PMC3209201.
Hoch JA. Regulation of the phosphorelay and the initiation of sporulation in Bacillus subtilis. Annu Rev Microbiol. 1993;47:441-65. doi: 10.1146/annurev.mi.47.100193.002301. PMID: 8257105.
LeDeaux JR, Yu N, Grossman AD. Different roles for KinA, KinB, and KinC in the initiation of sporulation in Bacillus subtilis. J Bacteriol. 1995 Feb;177(3):861-3. doi: 10.1128/jb.177.3.861-863.1995. PMID: 7836330; PMCID: PMC176674.
Hahn J, Roggiani M, Dubnau D. The major role of Spo0A in genetic competence is to downregulate abrB, an essential competence gene. J Bacteriol. 1995 Jun;177(12):3601-5. doi: 10.1128/jb.177.12.3601-3605.1995. PMID: 7768874; PMCID: PMC177070Arigoni F, Duncan L, Alper S, Losick R, Stragier P. SpoIIE governs the phosphorylation state of a protein regulating transcription factor sigma F during sporulation in Bacillus subtilis. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3238-42. doi: 10.1073/pnas.93.8.3238. PMID: 8622920; PMCID: PMC39589.
Yeak KYC, Boekhorst J, Wels M, Abee T, Wells-Bennik MHJ. Prediction and validation of novel SigB regulon members in Bacillus subtilis and regulon structure comparison to Bacillales members. BMC Microbiol. 2023 Jan 18;23(1):17. doi: 10.1186/s12866-022-02700-0. PMID: 36653740; PMCID: PMC9847131.
Imamura D, Zhou R, Feig M, Kroos L. Evidence that the Bacillus subtilis SpoIIGA protein is a novel type of signal-transducing aspartic protease. J Biol Chem. 2008 May 30;283(22):15287-99. doi: 10.1074/jbc.M708962200. Epub 2008 Mar 31. PMID: 18378688; PMCID: PMC2397457.
Illing N, Errington J. Genetic regulation of morphogenesis in Bacillus subtilis: roles of sigma E and sigma F in prespore engulfment. J Bacteriol. 1991 May;173(10):3159-69. doi: 10.1128/jb.173.10.3159-3169.1991. PMID: 1902463; PMCID: PMC207910.
Dong TC, Cutting SM. SpoIVB-mediated cleavage of SpoIVFA could provide the intercellular signal to activate processing of Pro-sigmaK in Bacillus subtilis. Mol Microbiol. 2003 Sep;49(5):1425-34. doi: 10.1046/j.1365-2958.2003.03651.x. PMID: 12940997.
Yu YT, Kroos L. Evidence that SpoIVFB is a novel type of membrane metalloprotease governing intercompartmental communication during Bacillus subtilis sporulation. J Bacteriol. 2000 Jun;182(11):3305-9. doi: 10.1128/JB.182.11.3305-3309.2000. PMID: 10809718; PMCID: PMC94525.
Campo N, Rudner DZ. SpoIVB and CtpB are both forespore signals in the activation of the sporulation transcription factor sigmaK in Bacillus subtilis. J Bacteriol. 2007 Aug;189(16):6021-7. doi: 10.1128/JB.00399-07. Epub 2007 Jun 8. PMID: 17557826; PMCID: PMC1952037.
Resnekov O, Losick R. Negative regulation of the proteolytic activation of a developmental transcription factor in Bacillus subtilis. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3162-7. doi: 10.1073/pnas.95.6.3162. PMID: 9501233; PMCID: PMC19712.
Nugroho FA, Yamamoto H, Kobayashi Y, Sekiguchi J. Characterization of a new sigma-K-dependent peptidoglycan hydrolase gene that plays a role in Bacillus subtilis mother cell lysis. J Bacteriol. 1999 Oct;181(20):6230-7. doi: 10.1128/JB.181.20.6230-6237.1999. PMID: 10515909; PMCID: PMC103754.
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