Abstract
The availability of numerous complete genome sequences of prokaryotes and several eukaryotic genome sequences provides for new insights into the origin of unique functional systems of the eukaryotes. Several key enzymes of the apoptotic machinery, including the paracaspase and metacaspase families of the caspase-like protease superfamily, apoptotic ATPases and NACHT family NTPases, and mitochondrial HtrA-like proteases, have diverse homologs in bacteria, but not in archaea. Phylogenetic analysis strongly suggests a mitochondrial origin for metacaspases and the HtrA-like proteases, whereas acquisition from Actinomycetes appears to be the most likely scenario for AP-ATPases. The homologs of apoptotic proteins are particularly abundant and diverse in bacteria that undergo complex development, such as Actinomycetes, Cyanobacteria and α-proteobacteria, the latter being progenitors of the mitochondria. In these bacteria, the apoptosis-related domains typically form multidomain proteins, which are known or inferred to participate in signal transduction and regulation of gene expression. Some of these bacterial multidomain proteins contain fusions between apoptosis-related domains, such as AP-ATPase fused with a metacaspase or a TIR domain. Thus, bacterial homologs of eukaryotic apoptotic machinery components might functionally and physically interact with each other as parts of signaling pathways that remain to be investigated. An emerging scenario of the origin of the eukaryotic apoptotic system involves acquisition of several central apoptotic effectors as a consequence of mitochondrial endosymbiosis and probably also as a result of subsequent, additional horizontal gene transfer events, which was followed by recruitment of newly emerging eukaryotic domains as adaptors.
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Abbreviations
- HGT:
-
horizontal gene transfer
- PCD:
-
programmed cell death
- TIR:
-
toll-interleukin receptor
- AIF:
-
apoptosis-inducing factor
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Acknowledgements
Not only the entire body of current literature on PCD, but even the subset that is directly relevant to the subject of the bacterial contribution to the origin and evolution of apoptosis, is vast. We appreciate the important work of all researchers in this area and apologize to those whose publications are not cited or are cited incompletely due to space considerations or to our inexcusable ignorance. This article is a ‘United States Government Work’ paper as defined by the US Copyright Act.
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Edited by G Melino
After submission of the manuscript of this study, it came to our attention that mitochondrial endosymbiosis and the origin of eukaryotic PCD could be linked in a straightforward hypothesis. The early α-proteobacterial endosymbionts might have been using secreted and membrane proteases, such as metacaspases, paracaspases and HtrA-like proteases, to kill their host cells once those became unhospitable environments, e.g. because of scarcity of nutrients. Such a mechanism could enable the endosymbionts to efficiently use the corpse of the assassinated host and move to another host. During subsequent evolution, this weapon of aggression might have been appropriated by the host and made into a means of programmed suicide, with the subsequent addition of regulatory components. In general terms, this idea has been proposed by Frade and Michaelidis (Frade JM, Michaelidis TM (1997) Origin of eukaryotic programmed cell death: a consequence of aerobic metabolism? Bioessays 19: 827–832).
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Koonin, E., Aravind, L. Origin and evolution of eukaryotic apoptosis: the bacterial connection. Cell Death Differ 9, 394–404 (2002). https://doi.org/10.1038/sj.cdd.4400991
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DOI: https://doi.org/10.1038/sj.cdd.4400991
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