Viral Genomes Are Part of the Phylogenetic Tree of Life

Home , Herpesviridae, Mimivirus, Orthoreovirus, White spot syndrome

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have no functional similarity to any known proteins, suggesting that Mimivirus diverged Viral genomes are part of the early in evolution9. This finding is by no means exclusive to Mimivirus; approxi- phylogenetic tree of life mately 60% of the ORFs of the bacteriophage sk1 genome have no known functional 10 Ethan B. Ludmir and Lynn W. Enquist homologues , as is the case with 94% of the white spot syndrome virus genome ORFs11. We propose that four criteria should In their recent review Moreira and López- without viruses; indeed, viral genomes have be considered when determining whether García presented ten reasons to exclude been implicated in many major evolutionary evolving genetic material is part of the viruses from the tree of life, with the milestones, from the introduction of DNA phylogenetic tree. Genomes and their gene fundamental assertion that ‘viruses are into the RNA world to the appearance of a products must be able to produce progeny not alive’ (Ten reasons to exclude viruses nucleus5–7. genomes, possess internal regulation, adapt from the tree of life. Nature Rev. Microbiol. Moreira and López-García also assert and respond to changing environmental 7, 306–311 (2009))1. This assertion is that the polyphyletic nature of viruses and conditions, and maintain structural organi- an oversimplification. Virions (physical the absence of any known ancestral viral zation; in other words, the genomes must virus particles) indeed are dead: they are lineages is sufficient reason to exclude their be capable of reproduction, self-regulation, inert and are driven solely by thermody- genomes from the tree of life1. This asser- adaptation and structural maintenance. The namically spontaneous reactions2. Yet, the tion discounts one of the most powerful first criterion, the ability to reproduce, is a phylogenetic tree is based on the genomic attributes of viral genomes: mutation rates property shared by all replicons; therefore, content of its component organisms, that are orders of magnitude higher than the other three criteria, self-regulation, adap- not the physical manifestations of these those for most cellular genomes2. This tation and maintenance, differentiate viral genomes3. Nucleotide sequences alone attribute increases the probability that new and cellular genomes from other replicating place a genome in the phylogenetic tree. genomes will survive virtually any selection genetic material. Accordingly, the question becomes: should and enables a viral population to survive Expression of information in viral viral genomes be included in this tree? We over a large span of time. Although it is genomes is highly regulated. Most DNA think so. difficult to determine common ancestors viruses, for example, have a timing Viral genomes are differentiated from for viral families that diverged countless mechanism for differential gene transcrip- other replicons and genetic material, such as generations ago, both sequence homology tion that is based on the replication cycle viroids or plasmids, through a unique three- and structural homology suggest that RNA (for example, early or late)2. Similarly, part strategy for survival that is common and DNA viral genomes stem from two Mononegavirales genomes use regulation to all viruses. First, viral genomes are pack- independent lineages8. Accordingly, viral of the viral RNA-dependent RNA polymer- aged into proteinaceous particles (virions). genomes do meet the Moreira and López- ase to differentiate synthesis of mRNA Second, the viral genome encodes all the García criteria: homology between members and replication of the genome12. All viral necessary information to allow completion of each of these two lineages forms the basis genomes have evolved complex techniques of an infectious cycle with a single cell, from for common ancestry1. for internal regulation (homeostasis), attachment and entry into a host cell to rep- However, Moreira and López-García such as genome polarity, transcriptional lication of progeny to egress. Third, the viral dismiss these arguments on the grounds that activators and protease modification of viral genome encodes gene products that ensure convergent evolution accounts for common polymerases. its stable propagation and maintenance in capsid symmetry and that horizontal gene Adaptation and responsiveness, which a host population. This tripartite strategy transfer (HGT) complicates reconstruction are inherently difficult qualities to assign separates viral genomes from other genetic of viral phylogenies1. Although convergence to genomes with short replicative cycles, material that does not encode a cellular indeed might account for the maintenance of are nevertheless attributes of information organism. capsid symmetry rules across a broad range encoded in viral genomes. Although virions Moreira and López-García maintain that of virions, non-structural gene products, themselves are ‘dead’, the viral genomes cellular organisms are capable of self- particularly replication proteins, are far more carried inside virions encode gene products maintenance and self-replication, but that important to the determination of phylog- that allow for adaptation and response to viruses are not1. Yet they include cellular enies. Homologies among these central units changing intracellular and extracellular con- obligate intracellular parasites, such as of genome replication provide evidence for ditions. In particular, these gene products Chlamydia and Rickettsia, in the tree of life4. common viral ancestry8. Additionally, HGT enable adaptation to host antiviral defences. This distinction was made because, unlike is not likely to be important in viral genome Two striking examples of responsiveness any viral genome, cellular intracellular evolution as only a small fraction of viral are Herpesviridae reactivation from latency, parasites encode their own ribosomes. It proteins have been suggested as possible a process that relies on cellular cues13, and is not clear why this fact precludes viral viral acquisitions from cells through gene prophage reactivation in lysogenic bacteria genomes from holding a place in the tree of transfer8. The sequencing of the Mimivirus after they receive signals of impending host life. If anything, the absence of remnants genome revealed a small number of cellular- cell death14. of ribosome-encoding genetic material derived metabolic genes9. Furthermore, Finally, Moreira and López-García assert in viruses highlights the evolutionary approximately two-thirds of predicted that viruses are examples of structural symbiosis of viral and cellular genomes on protein-coding genes (~600 open reading simplicity1. One need not look long at the a grander scale. It is difficult to imagine life frames (ORFs)) in the Mimivirus genome gallery of virions to see structural diversity,

not simplicity. Even in those virions that are not polyphyletic and are capable of being 7. Takahashi, I. & Marmur, J. Replacement of thymidylic acid by deoxyuridylic acid in the deoxyribonucleic acid share basic icosahedral and helical capsid traced back through two lineages. Above all, of a transducing phage for Bacillus subtilis. Nature symmetry, remarkable complexity has virions carry unique genetic material, unified 197, 794–795 (1963). 8. Forterre, P. The origin of viruses and their possible evolved to promote viral propagation. by a common tripartite replication strategy. roles in major evolutionary transitions. Virus Res. 117, A prime example of this is Orthoreovirus, The intricacies of each strategy, yet the com- 5–16 (2006). 9. Raoult, D. et al. The 1.2-megabase genome sequence for which structural complexity of the mon outcome, are testament to the distinctive of Mimivirus. Science 306, 1344–1350 (2004). virion (double layer capsid, replication and character of viruses and justify their inclusion 10. Chandry, P. S., Moore, S. C., Boyce, J. D., Davidson, B. E. & Hillier, A. J. Analysis of the DNA sequence, mRNA synthesis machinery at each of the into the phylogenetic tree. gene expression, origin of replication and modular 12 vertices) facilitates propagation of structure of the Lactococcus lactis lytic bacteriophage Ethan B. Ludmir and Lynn W. Enquist are at the sk1. Mol. Microbiol. 26, 49–64 (1997). the double-stranded RNA (dsRNA) Department of Molecular Biology, Princeton 11. Van Hulten, M. C. W. et al. The white spot syndrome genome without activating intrinsic host University, Princeton, 08544 New Jersey, USA. virus DNA genome sequence. Virology 286, 7–22 (2001). 15 e-mail: [email protected] cell defences against cytosolic dsRNA . 12. Whelan, S. P. J., Barr, J. N. & Wertz, G. W. Consider the Fullerene cone capsids of Transcription and replication of nonsegmented negative-strand RNA viruses. Curr. Top. Microbiol. HIV-1, the multi-membrane development 1. Moreira, D. & López-García, P. Ten reasons to exclude Immunol. 283, 61–119 (2004). of the vaccinia virion and the amazing viruses from the tree of life. Nature Rev. Microbiol. 7, 13. Liu, T., Khanna, K. M., Chen, X., Fink, D. J. & Hendricks, 306–311 (2009). R. L. CD8+ T cells can block herpes simplex virus type 1 architecture of archaeal virions that survive 2. Flint, S. J., Enquist, L. W., Racaniello, V. R. & Skalka, (HSV-1) reactivation from latency in sensory neurons. in ultra-extreme conditions, as well as the A. M. in Principles of Virology, Third Edition (ASM J. Exp. Med. 191, 1459–1466 (2000). Press, Washington DC, 2009). 14. Panet, A., Braun, E., Honigman, A. & Steiner, I. well-known bacteriophage T4 virion; all 3. Doolittle, W. F. Phylogenetic classification and Involvement of cellular death signals in the are testament to the reality of structurally the universal tree. Science 284, 2124–2128 reactivation of herpes simplex virus type 1 and (1999). lambda bacteriophage from a latent state. J. Theor. complex, diverse and functional systems to 4. Zomorodipour, A. & Andersson, S. G. E. Obligate Biol. 236, 88–94 (2005). protect and deliver genomes. intracellular parasites: Rickettsia prowazekii and 15. Reinisch, K. M., Nibert, M. L. & Harrison, S. C. Chlamydia trachomatis. FEBS Lett. 452, 11–15 Structure of the reovirus core at 3.6 Å resolution. Viral genomes represent essential elements (1999). Nature 404, 960–967 (2000). 5. Bell, P. J. Viral eukaryogenesis: was the ancestor of the of the phylogeny of life and have played nucleus a complex DNA virus? J. Mol. Evol. 53, 251 important parts in evolution. Viral genomes (2001). Acknowledgements 6. Forterre, P. The two ages of the RNA world, and the The authors thank M.P. Taylor, M.G. Lyman, O. Kobiler, meet the proposed four criteria for genomic transition to the DNA world: a story of viruses and T. Kramer and H. Prag Naveh for insightful comments regarding classification within the phylogenetic tree, cells. Biochimie 87, 793–803 (2005). this correspondence.