mechanisms of plant virus evolution

P1: NBL/sny P2: MBL/mkv QC: MBL/agr T1: MBL

June 23, 1997 11:18 Annual Reviews AR036-R AR036-11

Annu. Rev. of Phytopathol. 1997. 35:191–209Copyright c© 1997 by Annual Reviews Inc. All rights reserved

MECHANISMS OF PLANTVIRUS EVOLUTION

Marilyn J. RoossinckPlant Biology Division, The S.R. Noble Foundation, Post Office Box 2180, Ardmore,Oklahoma 73402-2180; e-mail: [email protected]

KEY WORDS: mutation, selection, recombination, reassortment, virus origins

ABSTRACT

Plant viruses utilize several mechanisms to generate the large amount of ge-netic diversity found both within and between species. Plant RNA viruses andpararetroviruses probably have highly error prone replication mechanisms, thatresult in numerous mutations and a quasispecies nature. The plant DNA virusesalso exhibit diversity, but the source of this is less clear. Plant viruses frequentlyuse recombination and reassortment as driving forces in evolution, and, occasion-ally, other mechanisms such as gene duplication and overprinting. The amountof variation found in different species of plant viruses is remarkably different,even though there is no evidence that the mutation rate varies.

The origin of plant viruses is uncertain, but several possible theories are pro-posed. The relationships between some plant and animal viruses suggests acommon origin, possibly an insect virus. The propensity for rapid adaptationmakes tracing the evolutionary history of viruses difficult, and long term controlof virus disease nearly impossible, but it provides an excellent model system forstudying general mechansims of molecular evolution.

“I’ve learned to think like a virus; no neurons, a lot of sex, and a lot of errors.”John J. Holland

INTRODUCTION

The diversity in nucleotide sequences among viruses, both within and betweenspecies, is enormous, especially compared to the divergence of most other life onearth. For example, two different individuals of the same plant virus isolate areoften more divergent at the nucleotide level than are humans and chimpanzees.

1910066-4286/97/0901-0191$08.00

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The RNA viruses of plants have also evolved numerous strategies for genomeexpression; they utilize divided genomes, subgenomic messenger RNAs, frame-shifting, stop codon suppression, poly-protein processing, overlapping readingframes, and signals for enhanced transcription or translation to regulate geneexpression (135). It is this capacity for diversity that makes viruses capable ofadapting to so many new niches. The mechanisms that viruses use to generatethis diversity are examined here.

Recently, a number of studies have estimated phylogenetic relationships be-tween extant viruses. The appropriate methodology for phylogenetic estima-tions of viruses is still an open question (85, 127) and must be considered verycarefully, as different methods can yield very different estimations (54–56).Special caution must be taken in analyzing more distantly related viruses (136).These studies can be useful, if carefully conducted, in understanding the evolu-tionary history of viruses. However, since viruses are constantly adapting andchanging, it is often possible to directly assess mechanisms of virus evolution.In the field of animal virology, numerous studies have looked at mutation rates,selection and fitness, the nature and biological significance of quasispecies,and mechanisms of reassortment and recombination. Similar studies with plantviruses have been more limited, and this review draws on some work in animalvirology and directs the reader to detailed reviews for further reading whereappropriate.

One challenge in writing about virus evolution is resolving the differencesin the definition of terms, so a few commonly used terms that are frequentlymisunderstood are defined here. For nucleotide or amino acid sequence com-parisons, “identity” obviously means identical; “similarity” is often used inter-changeably with identity in nucleotide sequences, but in amino acid sequencesit means having the same or similar structure and/or function (50). “Homology”means derived from the same origin; it does not address the degree of divergencesince the common origin, and hence it is strictly a qualitative term. Homologycan be difficult to distinguish conclusively from “convergence,” which meansevolving from different ancestors to provide a similar function. “Mutationrate” refers to the actual rate of misincorporation either by polymerase error orother means, whereas “mutation frequency” refers only to those misincorpora-tions that become established (and hence readily detectable) in the population(26).

DRIVING FORCES IN PLANT VIRUS EVOLUTION

Three major forces drive the evolution of viruses: mutation, recombination,and reassortment. These are essentially the same forces that drive all evolu-tion; recombination in viruses is analogous to recombination in meiosis, and

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VIRUS EVOLUTION 193

reassortment is analogous to chromosomal reassortment during sexual repro-duction. These forces generate diversity in viral genomes, providing variantsupon which natural selection can act. All these forces have been documented forplant viruses, and much information is available about the mechanisms of RNArecombination and reassortment. The mechanisms of mutation and selectionand what constitutes fitness are less well understood.

Mutation Rates and FrequenciesThe mutation or error rate of viral RNA-dependent RNA polymerase (RdRp)has not been measured for a plant virus, nor has it been measured in any intactorganism. Several studies have estimated the error rates of the RdRps of animalRNA viruses; these rates have averaged about 10−4, or one error per (10-kb)genome [reviewed in (26)]. This is generally accepted as the error rate ofRdRps, but this finding needs to be confirmed for plant viruses, and it alsoshould be examined in the context of a whole organism. Other factors suchas concentrations of magnesium or sodium chloride would likely effect errorrate, as shown for in vitro systems with thermal stable DNA polymerases (17).While in vitro systems allow dissection of complex biochemical reactions, theconditions of a cellular compartment cannot be accurately reproduced. Hencethe actual error rate of plant virus polymerases is still unknown. Cellular DNA-dependent DNA polymerases (DdDps) have error rates on the order of 10−9. Theabsolute requirement for basepairing before polymerization accounts for a largeportion of the fidelity of DdDps. Post-synthesis mismatch recognition increasesthe fidelity of DdDps. Since RNA polymerases do not require basepairing,as evidenced by their ability to initiate transcription without a primer, thislevel of proofreading is probably lacking, although RNA polymerase fromEscherichia colican excise and replace the last incorporated nucleotide, andthe accuracy of this process depends on ribonucleotide concentration (66).Although in vitro analysis of vesicular stomatitis rhabdovirus (VSV) RdRp invirions did not show any evidence of 3′–5′ exonuclease activity (123), this doesnot necessarily indicate that intracellular viral RdRps do not utilize some hostcomponent for a rudimentary proofreading activity. There has been no evidencefor or against any posttransciptional mismatch recognition in any RNA virusreplication. In addition to misincorporation, RdRps can probably introducevariation by replication slippage, which results in short repeats. Although nodirect evidence for this slippage exists, the presence of short repeats in someviral genes is very suggestive (52).

Other mechanisms for the introduction of mutations in RNA genomes havebeen shown for animal viruses. RNA editing by base modification is found inseveral animal viruses (51, 107, 132), and plant cells clearly utilize RNA editingmechanisms and contain the appropriate enzymes [reviewed in (119)], but RNA

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editing has not been described in a plant virus. Oxidative damage is a commonmechanism of mutation in DNA, and the genomic DNA of an average cell isestimated to receive about 10,000 hits per day, which are efficiently repairedby cellular machinery (34). Oxidative damage of RNA undoubtedly occursand inactivates TMV RNA in vitro (121, 122), but little work has been done inthis area; this type of modification in RNA has not been clearly demonstratedin vivo, nor is it known if cellular RNA repair systems exist (108). Clearly,however, the overall mutation rate of viral RNAs, whether from polymeraseerror or posttranscriptional modification, is probably near the disaster thresh-old, or viable maximum; chemical mutagenesis of viral RNA was unable tosignificantly increase the mutation frequency in two animal virus systems (60).

Although the mutation rate may be similar for all RNA viruses, the mutationfrequency varies dramatically for different viruses. Several studies have demon-strated the absence of significant variation in tobamoviruses (38, 90, 112–114),whereas the satellite tobacco mosaic virus has a much greater degree of diver-sity, even though it is replicated by the helper tobamovirus replicase (70). Ahigh degree of variation is also found in cucumber mosaic cucumovirus (CMV)and its satellite RNAs (3, 40, 71, 100, 103, 111). Interestingly, this differencein variation is reflected in the difference in host range; CMV has a very broadhost range, both experimentally and naturally (102), whereas the tobamoviruseshave a much narrower natural host range, although more plants can be infectedexperimentally than are found infected in nature [reviewed in (36)]. One canspeculate that the greater mutation frequency of CMV has allowed it to adaptto more niches (i.e. hosts). Among the luteoviruses, potato leafroll virus hasa very narrow host range and little variation, whereas beet western yellowsluteovirus has a much broader host range and much greater variation (18).The tenuiviruses, which have both a narrow host range and vector range, arelargely invariant, nor do they show evidence of reassortment or recombination(J deMiranda, personal communication).

The caulimoviruses are plant pararetroviruses; they package their genomes asDNA, but replicate via an RNA intermediate. The error rate of plant pararetro-virus replication has not been studied, but it is presumed to be similar to animalretroviruses, averaging about 1 error in 105 nucleotides [reviewed in (26)].There have been limited studies on strain variation within populations of theseviruses (63), but overall the caulimovirus isolates are quite similar (15). Vari-ation generated after passage (i.e. mutation fixation) of a caulimovirus clonewithin a single plant is about 4−6 × 10−4 changes per nucleotide (104).

The geminiviruses utilize the DNA replication machinery of the host andhence are presumed to have a high fidelity of replication (53). However, al-though careful studies of mutation frequency have not been done, geminivirusesappear to exhibit a considerable degree of sequence variation between strains,

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VIRUS EVOLUTION 195

both within and between populations (43, 124, 125), and they appear to have arapidly expanding host range. The source of this variation is not clear, and itmay reflect a lack of postreplication repair. The geminivirus DNA does not ap-pear to be methylated, since replication is inhibited by methylation (10); hence,the normal host mechanisms for mismatch repair probably do not function in thegeminivirus replication cycle. A study on mismatch repair of heteroduplex gem-inivirus DNA in tobacco protoplasts indicated that although U-G mismatches,which are frequently generated in DNA by cytosine deamination, were repairedto C-G at greater than 95% efficiency, T-G mismatches were not, and methyla-tion of one strand resulted in the preferential removal of the mispaired residuefrom the methylated strand, rather than from the unmethylated strand (64). Theauthors suggest that this could indicate that repair mechanisms in plants differfrom mammalian systems, which use methylation as a signal for template vsnewly synthesized strand, but it could also reflect a novel mechanism to intro-duce mutations by geminiviruses, which would insure maintenance, rather thanrepair, of an introduced mismatch. Mutations introduced by oxidative damagemay also escape host repair mechanisms, because either the viral DNA is se-questered in a compartment not available to repair machinery, or the cells inwhich the virus replicates have somehow shut off their normal repair mecha-nisms (L Hanley-Bowdoin, personal communication).

Some RNA plant viruses have exhibited hot spots for variation (69, 72, 100),but it is not known if this is due to regions of hypermutation by the polymerase,as occurs in the human immunodeficiency virus reverse transcriptase (65). Apotential strong secondary structure upstream of the CMV satellite RNA hyper-variable region suggests that polymerase pausing could account for variation inthis region (100). Alternatively, some types of RNA recombination (discussedbelow) can also introduce nontemplate nucleotides (12).

RecombinationRecombination events occur in both DNA and RNA plant viruses. Several re-cent reviews have documented the mechanisms of RNA recombination (73, 74,105, 120), and two recent issues ofSeminars in Virologyhave been devoted toRNA recombination (December 1996 and February 1997). The mechanisms ofRNA recombination have been largely elucidated by studying the formation ofdefective interfering RNAs (DI RNAs), or by repair of deleted viral genomes.They involve either homologous recombination between two nearly identicalRNAs, or nonhomologous recombination between two RNAs that have a shortantiparalell stretch of complementarity (120). Homologous recombination canbe either precise or imprecise, and the sequence context appears to controlcrossover precision (93). These three major types of RNA recombination cangenerate different types of diversity that selection can act upon. Homologous

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recombination can allow two viral genomes with different deleterious muta-tions to regenerate a functional genome. It can also allow related viruses toexchange genes in mixed infections, potentially generating ever more fit vari-ants. Phylogenetic analyses have yielded different estimations for the evolu-tionary relationships of RNA viruses when different genes are used, stronglysuggesting that recombination has played a very important role in their evolution(23, 42, 87). Evidence for recombination in the evolutionary history of plantRNA viruses has been demonstrated for luteoviruses (42), nepoviruses (76, 77),bromoviruses (1a), and cucumoviruses (35), and recombination events leadingto the formation of DIs have been demonstrated in several other virus systems(11, 78, 93, 94, 115, 128, 129). There is good evidence that recombination hasplayed a major role in the generation of the different luteovirus subgroups (42).

Recombination has also been important in the evolution of the plant pararetro-viruses. Caulimoviruses undergo recombination in vivo (61, 75), and phy-logeny estimations also suggest that recombination has been important in theevolution of these viruses (15). In addition, recombination between a cellulartransgene and cauliflower mosaic virus was recently demonstrated, and theserecombination events occur via template switching during reverse transcription(39, 118, 131).

DNA recombination is likely to be responsible for some of the variation seenin the geminiviruses. Evidence has been found for both homologous and non-homologous or illegitimate recombination, and includes release of infectiousviral DNA from monomer-containing recombinant plasmids; deletion of for-eign sequences; reversion of deletion mutants to wild-type genome size; andproduction of subgenomic (defective) DNA molecules. Nonhomologous re-combination results in deletions, insertions, and repetitions of viral sequences[reviewed in (8)].

ReassortmentSeveral families of plant RNA viruses use divided genomes as a strategy forcontrol of gene expression [reviewed in (135)]. In addition, the subgroup IIIgeminiviruses and banana bunchy top virus also have divided genomes. Inmany of these viruses artificially constructed reassortants, or pseudorecombi-nants, have proven very useful for genetic mapping of functional genes, andin some genera RNA segments can be exchanged between species. This haslong been proposed as a mechanism of introducing variation, especially sincemixed infections are so common among most field isolates of plant viruses, butit has been demonstrated in only a few systems. Phylogeny estimations of theCucumovirusgenus were different when the open reading frames (ORFs) foreach RNA were used separately, supporting the idea that reassortment had oc-curred during their evolutionary history. The isolation and characterization of

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a naturally occurring reassortant, containing RNAs 1 and 2 from peanut stuntcucumovirus and RNA 3 from CMV, confirmed that this occurred in nature(130). Two reassortants between tobacco rattle tobravirus and pea early brown-ing tobravirus were described by Robinson et al. The RNA 2 segment of thesereassortants contained the coding sequence of pea early browning virus, butthe 5′ and 3′ ends from tobacco rattle virus (110). RNA 3 of the cucumovirusdescribed above also contained the 5′ and 3′ ends of peanut stunt cucumovirus(MJR, unpublished results). Hence these viruses are both recombinant andreassortant in nature, with the 5′ and 3′ ends from the replicase-encoding virusbeing preserved. Although reassortment may not be a common event, as sug-gested by a recent survey of CMV in Spain (35), even a rare occurrence couldhave a dramatic impact on the evolution of new viral species, especially if thereassortant confers a selective advantage, such as an expanded host range. Thepropensity for reassortment probably also varies for different viruses. Sequenceanalysis and hybridization studies of peanut stunt cucumovirus suggest that re-assortment has been very common among different strains of this species (MJR,unpublished data; 62).

Gene DuplicationDuplication of a gene, followed by rapid divergence, usually to provide a newor modified function, is a common theme in the evolution of organisms withlarge genomes, but it has rarely been seen in plant viruses. There are twoinstances described. The closteroviruses have a duplication of their coat proteingene (9, 24), which has since diverged, and encodes a protein in the uniquetail-like structure at one end of the virion (1). Structural similarities in thecapsid proteins of the comoviruses suggest that the three genes encoding theseproteins also arose by duplication events, although there is little similarity atthe nucleotide level (117). Many other genes in plant viruses may also havearisen by duplication, but have since diverged beyond recognition.

OverprintingOverlapping ORFs are fairly common in plant viruses. In some cases, it ispossible to determine which ORF was probably the original gene, and whichone occurred by overprinting. If one ORF has similarity to an ORF of relatedviruses, whereas the other is lacking, one can speculate that the conserved ORFis most likely the original. This is the case with the two ORFs of RNA 2 ofthe cucumoviruses (21, 22). The large 2a ORF is highly similar to analogousORFs in the other members of theBromoviridae,whereas the smaller 2b ORF islacking in otherBromoviridae,indicating that the 2b ORF overprinting occurredafter the divergence of theCucumovirusgenus from the otherBromoviridae,but before the divergence of theCucumovirusspecies. A similar situation is

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found in the tymoviruses, and an analysis of codon bias in the overlap regionsupports the hypothesis that the replicase ORF is the original ORF (41).

Selection and FitnessNatural selection of the most fit variant is a basic concept of evolution, and inspite of more recent theories of neutral evolution (67), viruses appear to pre-dominantly follow Darwin’s original concepts of survival of the fittest. Fitnessis defined as the relative reproductive ability in a defined environment. Hence,the most difficult task in understanding selection is to define the environment,and to recognize that fitness in host A will not necessarily constitute fitnessin host B (58, 97). Every change in the environment or replicative niche ofthe virus may have different requirements for fitness. This becomes especiallyimportant in the many plant viruses that have a broad host range, or that can useseveral different vector species for transmission. Those viruses that replicatein both plants and in the insects that transmit them from plant to plant probablyhave dramatically different selection pressures in each host. Fitness of RNAviruses also involves more than just the coding sequences. It is clear that thenontranslated regions of viruses have important functions, and it is likely thatRNA structures within coding regions may also be biologically active. Manysatellite RNAs associated with plant viruses do not encode any protein [re-viewed in (116)], and the noncoding regions of other RNA viruses have beenshown to be functionally essential; hence this biological activity is completelydependent on the RNA, most likely on the secondary and tertiary structure. Theconstraints on the evolution of these molecules must also rely on their structure,as has been shown for the satellite RNA of CMV (37). The CMV helper viruscan exhibit a very strong selection for a particular satellite RNA when presentedwith a mixture, even though there is no apparent difference in replication com-petence for individual satellites. This selection varies, depending on the helpervirus (115a).

MULLER’S RATCHET Muller predicted that if mutation rate is high, and popula-tions are small, asexual populations will lose fitness in a ratchet-like manner witheach successive transfer (91). This concept has been tested in the RNA phageφ6, a dsRNA multipartite virus (13, 14), and in VSV, a (−) strand monopartiteanimal rhabdovirus (16, 58, 99). In both cases Muller’s prediction proved true.Although the ratchet was stochastic, overall fitness ratcheted down in very smallpopulation passages, whereas fitness increased dramatically in large populationpassages of VSV (98). Muller’s ratchet has not been tested for a plant virus butit has important implications in the natural evolution of plant viruses.

FITNESS AND VECTOR TRANSMISSION Many molecular studies in plant viruseshave used mechanical transmission for convenience, but natural transmission

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VIRUS EVOLUTION 199

of most plant viruses involves a vector, an insect, fungus, or nematode, andconsiderations of natural fitness must also include the constraints of the vector.The uptake of the virus by the vector always involves some degree of specificity,and the viral proteins must provide an appropriate “fit” for transmission to occur[reviewed in (49)]. Vector constraints on fitness probably increase with thoseplant viruses that also replicate in their insect vector, and the transmission ofsome plant viruses, such as potato leafroll luteovirus (126) and the tenuiviruses(19), may also involve bacterial and/or yeast-like symbiotes of the insect. Inessence, the natural environment of most plant viruses is very complex and isprobably rarely constant. Experimental infection can be much more controlled,and minimizing variation in the environmental niche of the virus can facilitateour understanding of evolutionary mechanisms, but it is essential to bear in mindthat the “real world” of the plant virus is very different from that of the mostlyuniform plants propagated in a controlled growth chamber or greenhouse.

Since population size affects fitness dramatically (13, 16, 58, 98, 99), withsmall population bottlenecks ratcheting down fitness, another considerationin vector transmission is whether or not this represents a genetic bottleneck.No studies have addressed this question. It does not seem likely that a viruswould evolve a mechanism of transmission that would continually result in aloss of fitness, and a recent review has proposed that helper-dependent vectortransmission evolved to ensure a large enough population passage to prevent theeffects of Muller’s ratchet (106). However, a number of plant viruses aretransmitted without helper components, including CMV, the plant virus withthe broadest known host range. Many multipartite viruses are transmitted ina nonpropagative, nonhelper-component manner, and these viruses require amultiplicity of infection greater than one to become established in a new host.These viruses have apparently found other mechanisms to ensure large enoughpopulation passages to prevent loss of fitness. DI RNAs are often found inexperimentally passaged RNA viruses and are easily generated by very largepopulation passages, but they are not generally found in nature. Usually, DIRNAs result in a loss of fitness, because they interfere with virus replication,probably by competition. Hence population passages that are too large mayeliminate purifying selection, and it is likely that natural transmission of plantviruses allows population passages somewhere between the small size thatwould result in a decrease in fitness and the very large size that results in theformation and maintenance of DI RNAs.

RNA VIRUSES AS QUASISPECIES

It is difficult to describe RNA and retroviruses in terms of classic population bi-ology because the potential for variation is so large. The concept of quasispecies

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was first proposed as a mathematically useful way to describe populations thatreplicate with a high error rate (32, 33). Numerous recent reviews have de-scribed the quasispecies nature of RNA virus populations (25, 27–31, 59, 89),and the general concept is described only briefly here. This concept is ex-tremely important in understanding the evolution of viruses, and the reader isencouraged to refer to the above-mentioned reviews.

In most instances, plant viruses have been described as a single sequence,usually derived from a cDNA clone of the virus. Although quite useful formolecular studies of gene function, data of this type must be used with greatcaution in understanding the mechanism of virus evolution. A single virus iso-late is not a single sequence, but a swarm of mutant sequences that vary arounda consensus sequence. The consensus sequence can only be obtained by directsequencing of viral RNA or DNA. The biological function of the virus dependson the mutant swarm, or quasispecies, and the unit upon which selection actsis the quasispecies. The swarm will center around a fitness peak or peaks,and variants with dramatically improved fitness will generally come from theedges of the swarm, or cloud. A major shift in the swarm would be predictedto occur when the environment undergoes a dramatic shift, such as transmis-sion of a plant virus to its insect vector in which it replicates. The biologicalimplications of the quasispecies nature of plant viruses are not known. Somebiological properties may depend on interactions between different variantswithin the swarm. Hence, the quasispecies nature of these viruses must alwaysbe borne in mind.

Although DNA viruses are often considered to have different populationdynamics because DdDps are generally much less error prone, the amountof variation observed in the geminiviruses suggests that they could also havea quasispecies nature. It will be interesting to see how these viruses generatehigh levels of variation while utilizing the host DdDp for replication (see sectionabove,Mutation Rates and Frequencies).

ORIGINS OF PLANT VIRUSES AND VIRAL GENES

An earlier review on plant virus evolution (47) proposed that some plant andanimal viruses could have had a common ancestor, based on amino acid andgenome organization similarity. Many more viruses have subsequently beencharacterized that fall into those same basic groups, and other plant viruses havebeen shown to be closely related to other groups of animal viruses. However,although many processes of the viral life cycle are common for plant and animalviruses, plant viruses have evolved some specific mechanisms: They must movethrough the plant, both cell to cell and systemically; and they are completelydependent on vectors for transmission (46).

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The cryptic viruses [reviewed in (86)] are small dsRNA viruses that are foundassociated with numerous plants. They are of evolutionary interest in that theydo not appear to move from cell to cell or to encode any transport function.They are transmitted by ovule and pollen to seeds, and they spread throughthe plant during cell division. These viruses could represent either virusesthat have lost their movement functions, or the precursors of modern plantviruses before they acquired transport functions. The dsRNA elements foundin some cultivars of barley are similar to cryptic viruses in that they appearto be transmitted vertically (133, 134), but no virus particles are associatedwith these dsRNAs. They could represent a further degenerate or precursor.Lucas & Wolf have proposed an intriguing model: Viral movement proteingenes may be derived from plant genes that encode proteins involved in thestructure/function of plasmodesmata (83). The lack of sequence similarityamong many movement proteins of viruses with other highly similar domains(92) indicates that they may have diverse origins. Support for this concept hasalso come from analysis of the KNOTTED1 homeodomain protein (KN1), aplant transcription factor. The KN1 protein is transported cell to cell via theplasmodesmata, and KN1 also mediates the selective transport of its mRNAthrough plasmodesmata (81), much like viral movement proteins facilitate virusmovement (82). Recombination between viral RNAs and plant chloroplastRNA described for potato leafroll luteovirus (84) illustrates that acquisition ofcellular RNAs is possible (see also the final section below).

The satellite RNA associated with bamboo mosaic potexvirus contains anORF coding for a nonstructural protein. This protein has a remarkably highdegree of similarity (46% at the amino acid level, 55% at the nucleotide level)with the capsid protein of satellite panicum mosaic virus (79), suggesting thatthese two functionally distinct proteins have a common ancestor. The greaterdegree of similarity in the nucleotides vs the amino acids suggests that theyhave diverged rapidly to perform different functions. The authors speculatethat these ORFs could have been acquired either from another virus infecting acommon host, or from a host gene transcript.

The debate about a monophyletic vs a polyphyletic origin for RNA viruseshas not been resolved. The monophyletic argument suggests that all RNAviruses have arisen from shuffling of an original set of domains, which arestill somewhat conserved in extant viruses, although often in different genomicarrays (48). The modular nature of viral genomes is suggested by phylogeneticestimations using different genes (23, 42, 87). Some of this variation in genomeorganization and apparent evolutionary history of virus genes could have arisenby long-term mixed infections where some genes of one virus were eventuallylost and replaced by the counterparts in the other virus. Pea enation mosaicvirus appears to be in the process of this type of evolution; RNA 1 is apparently

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derived from a luteovirus, whereas RNA 2, which encodes its own RdRp, ismore similar to carmoviruses and tombusviruses (20).

The polyphyletic argument says that the conservation of domains is due totheir origins from related genes found in different host plant cells, and that thevarious supergroups arose independently (48). Both arguments have validity,and a combination of the two alternatives probably reflects the actual historyof plant virus evolution; some domains, like the RdRp domain, may havehad a common ancestor, whereas others were acquired from hosts to providenew functions that allowed adaptation to new niches or to new mechanisms ofmovement and transmission.

Geminivirus DNA sequences have been found in the nuclear genome of to-bacco, as well as in some otherNicotianaspecies, and the rearrangements foundin these sequences implicate illegitimate recombination between viral and hostDNA (7). The distribution of these sequences inNicotiana species impliesthat geminiviruses first associated with these hosts before the cultivation oftobacco. A recent publication demonstrating complete replication of a gem-inivirus in Agrobacterium tumefacienssuggests that the geminiviruses arosefrom bacterial replicons (109). The initial association of geminiviruses withplants may have involved an integration event facilitated byAgrobacteriumor arelated bacteria. The geminiviruses may have acquired some host sequences inthe process, making them more adapted to replication in plant cells. The threesubgroups of geminiviruses could have subsequently diverged, or they couldhave arisen from similar but separate events.

A number of plant viruses, including reoviruses, marifiviruses, rhabdoviruses,tospoviruses, and tenuiviruses, replicate in both plants and in their insect vector.These viruses are more closely related to animal counterparts, and they mayrepresent an evolutionary link between the two. The theory of an arthropodvirus as a common ancestor to both plant and animal viruses has been proposed(45, 47, 68). TheNilaparvata lugensreovirus infects planthoppers, but it hasalso been identified in rice plants, where it appears to move systemically, butdoes not replicate (95). Thus the plant is the passive vector for this insect virus.This virus may represent an evolutionary bridge between the (progenitor) in-sect reoviruses and the plant reoviruses, which later evolved to replicate in theirplant vectors. Other viruses could have evolved from insect viruses by usingsimilar mechanisms, although the possiblity that some insect viruses evolvedfrom plant viruses must also be considered.

The evolutionary history of viruses can only be surmised from the extantspecies, but the theory of viruses as molecular fossils from an earlier precellularworld is attractive [reviewed in (5)]. Entities similar to viruses could well havebeen the precursers to more complex forms of life, but whether extant virusesevolved from those original forms or arose more recently is open to debate. It

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VIRUS EVOLUTION 203

is likely that viruses, or virus-like entities, have played an essential role in theevolution of life on earth, and they are certainly the most likely candidates forthe horizontal mobility of cellular genes, which has played a critical role in thevast diversity of life on earth (6).

PRACTICAL IMPLICATIONS OF PLANTVIRUS EVOLUTION

Viruses are extremely adaptable and are capable of rapid change. For ex-ample, after 10 months of adaptation by persistent infection in sandfly cells,VSV, an arthropod-borne virus, showed six orders of magnitude lower fitnessin mammalian cells, but a single passage in mammalian cells restored fitnessto near wild-type levels (97). However, in another study, VSV was unable toadapt to significantly overcome interferon-induced resistance, even under opti-mal large-population passages (96). These observations indicate that while anRNA virus can change dramatically and rapidly, some circumstances providean environment to which they cannot readily adapt. There is little informa-tion about generalized resistance to plant viruses that would be analogous tointerferon-induced resistance. Most recent strategies for resistance have usedpathogen-derived resistance, by expressing a viral gene in transgenic plants[reviewed in (4, 80)]. In general, pathogen-derived resistance is highly spe-cific. The mechanisms of this type of resistance are still being elucidated. Fewstrategies have been rigorously tested under the selection pressure of the natu-ral environment, and it seems likely that given the enormous plasticity of viralgenomes, many of these strategies may not succeed for more than a season ortwo in the field, just as virus-resistance genes introduced by classic breedinghave often failed. Perhaps a greater understanding of plant virus evolution willallow the manipulation of plants to provide a longer-lasting control of virusdisease, but it is unlikely that virus-free plants will ever become the agriculturalnorm. Current attempts to control viruses simply provide new selection pres-sures. Since disease provides few, if any, obvious selective advantages to thevirus, it may be more practical to consider ways to reduce or eliminate virus-induced disease without necessarily affecting virus load. Without the selectionpressure, the changes required to cause disease would be less likely to appear.

Another important evolutionary consideration in assessing the use of trans-genic plants for viral resistance involves risk. Recombination between trans-gene RNA and viral RNA has been clearly demonstrated [reviewed in (2)], andthe possibility of creating new pathogens, perhaps with different host ranges,should be carefully considered, although most opportunities for such eventsprobably already exist in mixed infections. Transgenically expressed CMVsatellite RNAs have been used for biocontrol because many strains attenuate

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viral symptoms, but recently an attenuating satellite RNA was shown to spon-taneously evolve to a more pathogenic variant (101, and references therein).

Finally, the ability of viruses to expand their host range is an important practi-cal effect of virus evolution. A number of recent emerging human viruses, suchas Ebola, human immunodeficiency lentivirus, and Sin Nombre hantavirus,have made headline news. Virus emergence is caused by several factors, in-cluding expanded host and vector range, human population increases, and therapid global movement of humans and their domesticated plants and animals.There have also been suggestions that increasing invasion of previously un-inhabited primary forests has allowed the release of new viruses [reviewed in(57, 88)]. Among the plant viruses, both the tospoviruses and the geminivirusescan probably be considered as emerging. Tosposvirus emergence is related totwo factors: These viruses appear to have recently evolved from an animalbunyavirus; and the host range of their vector, the Western flower thrip, hasexpanded dramatically in recent years (44). Other plant virus diseases will alsoundoubtedly emerge in the coming years, as environmental and climatic changesexpand insect ranges, agricultural practices change, and the global movementof humans and their plant products becomes ever more frequent and rapid.

The evolutionary strategies of plant viruses are just beginning to be under-stood. Clearly, extensive research is required in this area to provide compre-hensive knowledge about how these simplest forms of life have mastered thecomplex art of adaptation to an ever-changing world.

ACKNOWLEDGMENTS

The author thanks numerous colleagues who provided helpful discussions, in-sights, and unpublished data for this chapter: Richard Allison, David Bisaro,Stephane Blanc, Biao Ding, Stan Flasinski, Fernando Garc´ıa-Arenal, SaidGhabriel, Stewart Gray, Linda Hanley-Bowdoin, John Holland, Andy Jackson,Gael Kurath, Bill Lucas, Ulrich Melcher, Joachim deMiranda, Rick Nelson,Keith Perry, Tom Pirone, and ME Christine Rey.

Visit the Annual Reviews home pageathttp://www.annurev.org.

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mechanisms of plant virus evolution

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