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Further, we show that this clade of ATP-grasp domains additionally includes two previously unknown, related prokaryotic families with potential roles in distinct biological conflict systems [ 20- 22].
Studies in the past decade are pointing to certain unifying themes across the proteinaceous toxins deployed in each of these distinct types of biological conflict.
Genomic analysis has also revealed that the richest source of proteinaceous toxins is the bacterial superkingdom, wherein several systems involved in most of the levels of biological conflict enumerated above are encountered [ 4, 6, 17, 18, 21, 22, 25].
The HEPN domains, similar to several other RNase domains found in biological conflict systems [ 1, 2, 10, 35], was also recruited as a core RNA processing enzyme, Las1, whose fixation might have enabled the emergence of the unique structure of the eukaryotic 5.8S-25S/28S rRNA precursor [ 55].
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These have been separated into nine major categories; namely Biological, Conflicts, Environmental, Interest, Legislation, Market, Operational, R&D, and Vandalism.
Similarly, the R2K.2 and R2K.3 families are also proposed to participate in biological conflicts, probably between bacteriophages and their hosts.
Similarly, the two other prokaryotic R2K clade families are also proposed to participate in biological conflicts between bacteriophages and their hosts.
Recent studies indicate that many of the RNases related to those that participate in biological conflicts are involved in core cellular functions as RNA-processing enzymes.
Furthermore, HEPN domains might have been encoded by fast-evolving mobile elements involved in biological conflicts even in the LUCA if not at earlier stages of evolution.
Thus, the RNase activity of HEPN domain could be a unifying theme shared by cellular RNA maturation systems and those involved in biological conflicts.
Thus, the study of RNase domains involved in biological conflicts also often throws light on the functions and molecular mechanisms of RNases participating in core cellular processes.
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