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Viral and Stem-Loop RNA Consortia Promote Life

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Viral and Stem-Loop RNA Consortia Promote Life nyas12565 W3G-nyas.cls October 15, 2014 19:48 NYAS nyas12565-1655000 Dispatch: October 15, 2014 CE: Journal MSP No. No. of pages: 10 PE: Lia Zarganas 1 Ann. N.Y. Acad. Sci. ISSN 0077-8923 2 3 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 4 Issue: DNA Habits and Their RNA Inhabitants 5 6 Force for ancient and recent life: viral and stem-loop RNA 7 8 consortia promote life 9 10 Luis P. Villarreal 11 Center for Virus Research, University of California, Irvine, California 12 13 Address for correspondence: Luis P. Villarreal, Department of Molecular Biology and Biochemistry, University of California, 2208 Bio. Sci III, Irvine, CA 92697. [email protected] 14Q1 15 16 Lytic viruses were thought to kill the most numerous host (“kill the winner”). But persisting viruses/defectives can 17 also protect against viruses, especially in a ubiquitous virosphere. In 1991, Yarmalinsky et al. discovered the addiction 18 modules of P1 phage, in which opposing toxic and protective functions stabilize persistence. Subsequently, I proposed 19 that lytic and persisting cryptic virus also provide addiction modules that promote group identity. In eukaryotes (and 20 the RNA world), a distinct RNA virus–host relationship exists. Retrovirurses/retroposons are major contributors 21 to eukaryotic genomes. Eukaryotic complexity appears to be mostly mediated by regulatory complexity involving 22 noncoding retroposon-derived RNA. RNA viruses evolve via quasispecies, which contain cooperating, minority, 23 and even opposing RNA types. Quasispecies can also demonstrate group preclusion (e.g., hepatitis C). Stem-loop 24 RNA domains are found in long terminal repeats (and viral RNA) and mediate viral regulation/identity. Thus, 25 stem-loop RNAs may be ancestral regulators. I consider the RNA (ribozyme) world scenario from the perspective 26 of addiction modules and cooperating quasispecies (i.e., subfunctional agents that establish group identity). Such 27 an RNA collective resembles a “gang” but requires the simultaneous emergence of endonuclease, ligase, cooperative 28 catalysis, group identity, and history markers (RNA). I call such a collective a gangen (pathway to gang) needed for 29 life to emerge. 30 Keywords: virus; evolution; group selection; cooperatively; origin of life; gangen 31 32 33 34 The ever-present virosphere we are led to think of consortia, not clones, as the 35 more fundamental features of life. This perspective All living habitats (including prebiotic ones) have 36 also includes the characteristics of both competition and must operate in a virosphere (a network of in- 37 and symbiosis, as viruses are inherently symbiotic fectious genetic agents). The authentic survivability 38 parasites that can also compete fiercely (killing or of life must also be measured in the virosphere. 39 protecting host). Although the realization of the ubiquity, scale, and 40 diversity of the virosphere is a rather recent de- 41 Dark matter of the virosphere: persistence velopment, it still identifies a fundamental feature 42 applicable to all life. However, most experimental Viruses can transfer genes between themselves and 43 paradigms seek to eliminate or have ignored viruses. their host. However, it is much more common 44 For example, when we clone Escherichia coli free of that they transfer virus-derived information to 45 temperate and lytic phage or when we establish a their host, as demonstrated by any metagenomic 46 sterile mouse colony free of all the usual persis- analysis.1 Stable transfer of the entire information 47 tent viruses, we create a misleading virus-free habi- content of the virus is a definition of virus persis- 48 tat for the survival of life. I suggest that, to bet- tence. But even transfer of partial (defective) viral 49 ter understand the origin and evolution of life, we information can lead to virus–host persistence at 50 must instead adopt a virus-first perspective. In such a population level. Thus, viruses often stably col- 51 a perspective, the persistence of virus information onize their host and persist (symbiosis). Viruses 52 becomes key. It is through such a perspective that can also kill their host, but persistent viruses can doi: 10.1111/nyas.12565 Ann. N.Y. Acad. Sci. xxxx (2014) 1–10 C 2014 New York Academy of Sciences. 1 nyas12565 W3G-nyas.cls October 15, 2014 19:48 1 Force for ancient and recent life Villarreal 2 3 protect their host from the very same (or simi- path to cooperation via the combination toxic de- 4 lar) virus. It is asserted here that, together (virus structive (lytic) action and counteracting protective 5 killing and virus protection), we see a truly cre- (immune) action. P1 is a stable episomal prophage 6 ative and cooperative force in the evolution of life of E. coli that is ubiquitous in wild isolates and has 7 that is fundamentally both symbiotic and competi- long been studied for its ability to interfere with 8 tive but affects populations, not simply individuals infections by other phage.3 Initially, P1 was con- 9 (due to virus transmission). Since virus persistence sidered as a plasmid, but its recognition as a per- 10 is exceedingly common but usually a silent state, sistent and lysogenic phage was soon realized. The 11 it represents a large but mostly unnoticed force in mechanism for this stability was first discovered by 12 evolution—the dark matter of biology. In addition, the Yarmolinski group at NIH in the 1990s after Q2 13 viruses will spontaneously parasitize themselves by many years of study of postsegregation killing.4 The 14 generating defective virus. Such defective parasites virus stability is mediated by an addiction module 15 of viruses appear to be “junk” to most observers, and that comprises a stable protein toxin and a less sta- 16 are indistinguishable in function or consequence ble protein antitoxin that are coregulated and act 17 from what we call transposons. The persistence of in coordination.5–7 Loss of plasmid (virus) during 18 such defective parasites can, nevertheless, also pro- cell division into daughter cells leads to the killing 19 vide protection against virus killing. Thus, the per- of the “cured” cells by the stable toxin. The ability 20 sistence of virus information can promote virus– of the P1 addiction module to induce postsegrega- 21 host survival yet also provide survival advantage to tion killing, however, also involves the cells’ own 22 populations that retain the ability to produce lytic programmed cell death systems, such as the mazEF 23 virus and kill competitor populations.2 This virus– toxin/antitoxin gene pair.8 Indeed, it has been pro- 24 host dynamic is an ancient, ongoing, and inherently posed that this self-killing (programmed cell death), 25 symbiotic force in evolution. Together, these oppos- besides insuring maintenance of P1 prophage, can 26 ing functions of protection and killing provide and be a defense mechanism that inhibits the lytic spread 27 define an acquired host group identity. Such group of P1.9 Such observations led me to generalize the 28 identity allows subfunctional consortia to attain a concept of P1 addiction from a process that insures 29 combined greater competence and operates via a the specific maintenance of P1 and promotes its 30 dynamic, consortial, and history-dependent mech- survival to one in which combinations of persist- 31 anism. Thus, a main objective of this communica- ing cryptic prophage (often hyperparasites) will to- 32 tion is to experimentally justify and further clarify gether provide resistance of the colonized host to 33 this perspective and to extend this thinking into a diverse set of viruses, such as those in the ever- 34 the RNA world. As it fundamentally involves non- present virosphere.10–13 The presence of P1 will kill 35 linear consortia (networks), understanding it will cells infected by other phage. P1 itself can be colo- 36 be counter-intuitive and difficult. This perspective nized by IS2, which can interrupt addiction modules 37 depends on an ever-present virosphere, which pro- and change the host–virus relationship with other 38 vides a creative–destructive combination force for viruses.14 Interestingly, similar insertions of IC re- Q3 39 the origin and development of life. However, the striction systems into P1 can also be seen as linked to 40 real power of the consortial action of genetic par- the horizontal spread of DNA restriction systems.14 41 asites will be best understood through the action Since such states involving genetic parasites being 42 of stem-loop RNA. These simple ancestors to life colonized by other genetic parasites are very com- 43 and viruses are particularly competent to function mon and they can significantly affect the relation- 44 as consortia. ship of the colonized host with other viruses, I have 45 previously called this a hyperparasite colonization A main strategy for the persistence 46 that provides a network-based virus–host system af- of parasitic information is the addiction 47 fecting its viral ecology.2,10 This raises the interesting module 48 question of how an addiction system (like P1) might 49 Addiction modules were initially identified through be modified by yet further colonization. Clearly, cell 50 the study of episomal DNA phage. Addiction mod- death would need to be prevented by new colonizers. 51 ules define a core strategy for virus persistence, but I have argued that these viral (and subviral) agents 52 also lead us to understand how viruses provide a are the principal mediators of acquired host group 2 Ann. N.Y. Acad. Sci. xxxx (2014) 1–10 C 2014 New York Academy of Sciences. nyas12565 W3G-nyas.cls October 15, 2014 19:48 1 Villarreal Force for ancient and recent life 2 3 identity. But besides affecting host and group sur- lective function and group identity.
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