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Medical Hypotheses (2005) 65, 868–872 http://intl.elsevierhealth.com/journals/mehyOrigin and evolution of viruses: EscapedDNA/RNA sequences as evolutionaryaccelerators and natural biological weapons a,*Ivan Bubanovic , Stevo Najman b, Zlatibor Andjelkovic ca Department of Obstetrics and Gynecology, Medica Centre, Novosadska 1/c, 18000 Nis, Serbia,Serbia and Montenegrob Institute of Biology, Medical Faculty, University Medical School, Nis, Serbia and Montenegroc Institute of Histology, Medical Faculty, Pristina, Kosovska Mitrovica, Serbia and MontenegroReceived 15 April 2005; accepted 12 May 2005Summary Knowledge of the origin and evolution of viruses could provide a better understanding of a number ofphenomena in the ﬁeld of evolution such as the origin and development of multi-cellular organisms, the rapiddiversiﬁcation of species over the last 600–700 million years and the lack of transitional forms in the evolution of species(‘‘missing links’’) etc. One of the possible effects of escaped DNA/RNA sequences or viruses on the evolution of multi-cellular organisms, especially vertebrates, could be the phenomenon of horizontal transmission and dissemination ofgenes. Interestingly, if so, this effect could be considered as a model of primeval and natural genetic engineering. Otherpossible links between the evolution of multi-cellular organisms and viruses are connected with the fact that virusesrepresent the source of different forms of selective pressure such as epidemics of infectious diseases, autoimmunity,malignant alteration, reproductive efﬁciency, etc. At the same time, these two models of ‘‘long-term evolutionaryrelations’’ could represent ‘‘key factors’’ in the evolution between viruses and multi-cellular organisms. The capabilityof a genome to produce and emit DNA/RNA sequences or de novo created viruses which can be a vector of geneshorizontal transmission and/or cause selective pressure on concurrent or predator species gives a new characteristic toviruses – the possibility of their acting as natural biological weapons. Finally, possibly evolutionary advantages of thisgenome capability could be one of explanations for the phenomena such as genome instability and its ability to emitDNA/RNA sequences and/or de novo created viruses, as well as evolutionary conservation of this unique phenomena.c 2005 Elsevier Ltd. All rights reserved.The origin and evolution of viruses mostly unknown. Our knowledge concerning their origin is lost in a sea of conjecture and specula-In contrast to other microbes and multi-cellular tions, hardly supported at all with precise scientiﬁcorganisms, the origin and evolution of viruses is evidences. For example, viruses have never been detected as fossil particles, probably because they * Corresponding author. Tel.: +381 1849 178. are too small and too fragile to succumb to fossil- E-mail address: firstname.lastname@example.org (I. Bubanovic). ization processes. Even in fossilized biological 0306-9877/$ - see front matter c 2005 Elsevier Ltd. All rights reserved.doi:10.1016/j.mehy.2005.05.038
Origin and evolution of viruses 869materials such as plant leaves or insects in amber, tion of evolutionary processes, which could resultpreserved nucleic acid sequences of viruses have in rapid diversiﬁcation of species and sometimesnever been detected. Hence, evolutionists are lim- quicker and better adapting to environmental con-ited in their ability to precisely reconstruct an evo- ditions; (iii) the possibility that de novo createdlutional history of viruses. However, in spite of all viruses can act as natural biological weaponsthe difﬁculties in understanding their origin and against predator and/or concurrent species.evolution, several theories more or less success- There are a number of complex molecular lifefully explain the basic observed facts [1–3]. forms that blur the boundaries between cells and Due to the fact that the genome of viruses viruses. Also, there are pieces of self-replicatingunderlies mutation and genetic recombination, genetic material found in bacteria, e.g., episomes,viruses probably evolve according to a form of nat- which evolve independently of their hosts, and canural selection, very similar to that governing other even move from one host to another – but carryliving things. It seems that this simple fact may genetic information that may be toxic or beneﬁ-well provide enough support for scientiﬁc accept- cial, even essential, to their host. In the case ofability of several commonly discussed hypotheses the beneﬁcial role of episomes, many bacteriaon virus origin and evolution. Currently, there are would be unable to reproduce at all without them.three such hypotheses. The ﬁrst hypothesis is the Episomes are, in many ways, quite similar toso-called theory of ‘‘regressive evolution’’, which viruses – except that they only reproduce them-proposes that viruses descend from free-living selves when their hosts do, whereas viruses repro-and more complex parasites. According to this the- duce themselves hundreds of times, causingory, ancestral viruses developed a growing depen- disease. According to this way of thinking, virusesdence on host-cell intracellular ‘‘machinery’’ probably co-evolve with their hosts, like any ‘‘goodthrough evolutionary time, while retaining the abil- parasite’’. There appears to be quite a lot of justi-ity to auto-replicate, like mitochondria that have ﬁcation for this idea, especially from studies oftheir own genetic information and replicate on viruses such as papilloma viruses, endogenous ret-their own [2–4]. The second hypothesis is the so- rovirus-like sequences in animal genomes, and her-called theory of ‘‘cell origin’’, which assumes that pes viruses. For example, the divergences ofviruses reﬂect their origin from cell DNA and/or primates and of birds related to chickens have beenmessenger RNA, which acquired the ability to traced by comparing the types and sequences ofauto-replicate, create extracellular virions, exist retroviral-derived sequences in their genomes. Itand function independently. Finally, there is the has also been repeatedly shown that the closesttheory of ‘‘independent’’ or ‘‘parallel’’ evolution relatives of human papillomavirus types infectingof viruses and other organisms, which assumes that particular tissue types (e.g., cutaneous wart types,viruses appeared at the same time as the most genital mucosal types) are those viruses infectingprimitive organisms [1,3,4]. similar tissue types in other primates, indicating Whatever the advantages and disadvantages of that these tissue preferences were well establishedeach theory are, the ability of every cell (excluding before the divergence of humanoid apes from thecells without a nucleus, e.g., the erythrocytes of primate line [1,3,4].mammals) to release DNA/RNA sequences or denovo created viruses is unique and amazing. Atthe same time, the cell’s ability to release DNA/ Viruses as evolutionary acceleratorsRNA sequences shows a high level of evolutionaryconservation. These facts might be well enough The model of living beings evolving based on gen-motifs for identiﬁcation of positive selective pres- ome changes and the ability to adapt to positivesure that could be linked with this genome ability, and/or negative selection pressures is widely ac-as well as a highly important thesis for better cepted among evolutionists. However, it is hardunderstanding of origin and evolution of viruses, to imagine that the evolution of life is based onand even life as we know it [3–5]. Several factors accidental and isolated gene mutations and thatof positive selective pressure could play important this model of evolution ﬁnally brought about therole in development and evolutionary ‘‘symbiotic’’ form of life we know today. One of key argumentslinking (conservation) of genome and its ‘‘instabil- against a model of evolution based on the acciden-ity’’, which is probably responsible for cell ability tal changes of isolated genes is the simple fact thatto emit de novo created viruses: (i) the possibility gene mutation is a relatively rare event and hence,of horizontal and vertical dissemination of gene according to this model, evolution would be veryblocks, and their incorporation into the cell gen- slow. Many evolutionists argue that life on theome of new hosts; (ii) the possibility of accelera- Earth would still be at the bacteria and seaweed
870 Bubanovic et al.stage, if genetic changes were based only on acci- takes whole blocks of genes and moves them to dif-dental changes of isolated genes. Considering the ferent locations. These new locations could befact that most mutations are sources of negative elsewhere in the same genome or in the genomeselective pressure, the minor percentage of acci- of a different host. One of recombination mecha-dental mutations of genes that might cause posi- nisms is transduction by viruses that works in bothtive selective pressure, theoretically, could not prokaryotic and eukaryotic organisms. The discov-result in the evolution of living beings and the ery that large blocks of genetic instructions candiversity of species that we know today. Certainly, be swapped and transferred among living beingsthis opinion does not completely exclude participa- is a clue that the insertion of new genes could betion of accidental isolated gene changes in the evo- the mechanism that assists evolution. If viruseslutionary processes, but the inﬂuence of these can transfer eukaryotic genes across speciesevents on the evolution of life probably is minimal boundaries, and can install their own genes intoand marginal [3,4,6]. their hosts, the case for the new mechanism is even With the exception of the mutations of isolated stronger. Viruses do just that [1,3,4,6,7].genes, several different mechanisms can lead togenome changes. These mechanisms are recombi-nation, transposition, translocations, inversions,deletions, duplications, transduction and other Viruses as natural biological weaponunpredictable, chaotic and yet unremarkable ge-netic events which, in contrast to mutations, lead From the standpoint of medical science, instabil-to great changes of genome. Signiﬁcant genetic ity is a highly undesirable feature of a genome aschanges can probably result in ‘‘great evolutionary it is very often a source of malignant alterationdisplacement’’ and acceleration of evolutionary of cells, spontaneous abortion, autoimmunity,processes. Incidentally, this hypothesis might rep- genetic diseases, emerging and even the re-resent an acceptable explanation for the many emerging of new viruses. In contrast to this,‘‘missing links’’ in palaeontology and the state of speaking in a Darwinian sense, the evolutionaryour knowledge regarding the origin of life and spe- advantages of genome instability are probablycies. Put quite simply, what we call the ‘‘missing more important than potential and real negativelinks’’ probably never existed, due to ‘‘rapid’’ consequences of this phenomenon. In addition,and large-scale changes which, for as yet unknown emitted DNA/RNA sequences and/or de novo cre-reasons, have implicated, from time to time, every ated viruses can operate as natural biologicalliving creature in the last billion years. Conse- weapons against predator and/or concurrent spe-quently, we can conclude that the evolution of liv- cies. This possibility could also be the source ofing beings probably has not been based on gradual positive selective pressure supporting evolution-and ‘‘ﬁne’’ passing forms. In this story, viruses ary conservation of features such as genomecould be an important factor in the theory of ‘‘ra- instability and its ability to emit its own se-pid and big evolutionary steps’’ based on great quences [8–11].changes of genome. Several mechanisms might be Viruses apparently can, and obviously do, makeincluded in this evolutionary scheme: (i) horizontal big jumps in hosts every now and then. It seems al-transmission of genes between individuals of iden- most certain, for example, that arthropods are thetical or even different species; (ii) vertical trans- original source for a number of virus familiesmission of genes and bi-directional vertical infecting insects and mammals – such as the Flavi-transmission between mother and offspring in viridae – and probably also of viruses infecting in-viviparous species; (iii) genome destabilization sects and other animals and plants – such as theand induction of new changes of genome; (iv) Rhabdoviridae and Reoviridae. For example, picor-increasing genome instability. Finally, the advanta- naviruses of mammals are very similar structurallyges of the rapid evolution of living beings and a and genetically to a large number of small RNApossible link of this phenomenon with viruses could viruses of insects and to at least two plant viruses,be an acceptable explanation for the ‘‘symbiotic’’ and – as the insect viruses are more diverse thanconnection of the genomic ability to emit DNA/RNA the mammalian viruses – probably had their originsequences and/or de novo created viruses. This in some insect that adapted to feed on mammalsphenomenon could lead to evolutionary conserva- (or plants) at some distant point in evolutionarytion of genome instability as a universal genome time. The majority of existing viruses relevant tocharacteristic [6,7]. humankind are zoonozis. In spite of the fact that Recombination is a far more powerful way for animals are the source of many viruses pathogenicDNA to change. This model of genome remodelling to humans, the most important factor in the
Origin and evolution of viruses 871dissemination of viruses is the fact that humans hunting and killing the two smaller species oflive in a manner which increases the possibility of monkey .transmission of new viruses from their endogen The hypothesis that HIV evolved from SIV ishosts (animals) to humans. Rodents and arthropods based on the many similarities between theseare also included in transmission of viruses from two viruses, especially at the genetic level. Theone species to another, especially in an urban two viruses are genetically very similar and aremilieu where their vector role is multi-ampliﬁed. transmitted in the same way. However, HIV onlyOther animals, especially primates, represent causes AIDS in humans and SIV only causes AIDSimportant sources of viruses potentially pathogenic in monkeys. The SIV virus, like HIV, is found infor humans. In this context, we can mention a few blood. This can provide support for the beliefemerging or even re-emerging, new extremely that HIV entered man via monkey’s blood. Forvirulent and dangerous viruses which cause dis- this, possible routes include drinking the bloodeases such as Ebola, Marburg and Congo-Crimean of monkeys, eating raw monkeys or perhaps di-haemorrhagic fever, Hantavirus lung syndrome, rect exposure of humans to monkey bloodKorean haemorrhagic disease, SARS-Co virus, and [13,14,16]. Finally, the possibility of interspeciesof course, HIV1 and HIV2 [1,3,4,7]. sexual transmission cannot yet be excluded. HIV is important problem for humankind andalso a good example that can support our hypoth-esis on viruses as natural biological weapons. It isnow generally accepted that HIV is a descendant Conclusionof simian immunodeﬁciency virus (SIV). Certainsimian immunodeﬁciency viruses bear a very close The opinion that viruses simply cause infectiousresemblance to HIV-1 and HIV-2. For example, diseases is over-simpliﬁed and archaic. Their roleHIV-2 corresponds to a simian immunodeﬁciency in nature and their inﬂuence on the evolution ofvirus found in the sooty mangabey monkey other living things is probably of greater and,(SIVsm), widely known as the green monkey, even, crucial importance. The ability of a gen-which is indigenous to western Africa. The more ome to emit de novo created viruses and the evi-virulent strain of HIV, namely HIV-1, was, until dent evolutionary conservation of this propertyvery recently, more difﬁcult to place. The closest strongly suggests that emitted DNA/RNA se-counterpart that had been identiﬁed was the sim- quences could be important in the evolution ofian immunodeﬁciency virus that was known to in- life. Practically, this means that viruses couldfect chimpanzees (SIVcpz), but there were be important sources of positive selection pres-signiﬁcant differences between it and HIV. In sure on certain species, thus opening up the pos-addition, it was reported that frozen tissue taken sibilities of: (i) horizontal dissemination of genes;from a chimpanzee carried a simian virus (SIVcpz) (ii) rapid and large-scale evolutionary changes bywhich was almost identical to HIV-1. The chim- way of unstable genomes; (iii) a role as biologicalpanzee came from a sub-group of chimpanzees weapons directed against concurrent and/orknown as Pan troglodytes troglodytes, which were predator species.once common in west-central Africa. It is claimedby some researchers that this shows that thesechimpanzees were the source of HIV-1, and thatthe virus at some point crossed species from chim- Referencespanzees to humans. However, it was not necessar-  Margulis L, Sagan D. Microcosmos: four billion years ofily clear that chimpanzees were the original evolution from our microbial ancestors. University ofreservoir for HIV-1 because chimpanzees are only California Press; 1997.rarely infected with SIVcpz. Also, there is opinion  Desjardins C, Eisen JA, Nene V. New evolutionarythat wild chimps became infected simultaneously frontiers from unusual virus genomes. Genome Biolwith two simian immunodeﬁciency viruses (SIVs) 2005;6:212–3.  Margulis L. Symbiotic planet: a new look at evolu-that had ‘‘viral sex’’ to form a third virus capable tion. Basic Books; 2000.of infecting humans and causing AIDS [12–15].  Margulis L, Sagan D. What is life? University of CaliforniaSharp et al.  discovered that the chimp virus Press; 2000.was an amalgam of the SIV infecting red-capped  Vandamme AM. Phylogenetic techniques improve ourmangabeys and the virus found in greater spot- understanding of virus evolution. Infect Genet Evol 2005;5(3):197–200.nosed monkeys. The authors believe that the  Singh ND, Petrov DA. Rapid sequence turnover at anhybridisation took place inside chimps that had intergenic locus in Drosophila. Mol Biol Evol 2004;21:become infected with both strains of SIV after 670–80.
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