1. Viral Mutation Rates

Rafael Sanjuán

Spontaneous mutations resulting from uncorrected replication errors, edition of the genetic material, or spontaneous nucleic acid damage are the primary source of genetic diversity, and central to the evolutionary process. Viruses show ample variation in their rates of spontaneous mutation. RNA viruses show extremely high rates whereas DNA viruses mutate more slowly, yet still considerably faster than their hosts. This chapter addresses the molecular mechanisms underlying the production of spontaneous mutations in viruses, such as polymerase infidelity, lack of proofreading, avoidance of post-replicative repair, or host-mediated nucleoside deamination. The evolution of viral mutation rates is also addressed, focusing on the association between mutation rates and other basic genomic properties, on how viruses can modify replication fidelity in response to selection, and on the ability of viruses to optimize mutation rates for maximal adaptability. Finally, some implications for pathogenesis, the emergence of drug resistance, and vaccination are discussed.

2. Viral Informatics: Tools for Understanding the Evolution of biology's Most Varied Genomes

Siobain Duffy

Our understanding of viral molecular evolution is being advanced by a combination of massive amounts of sequencing data and statistical algorithms that can extract information from them. Classic and modern approaches to phylogenetics, population genetics and other evolutionary analyses are reviewed. The sometimes conflicting language and desires of computational scientists and virologists as they approach the same issue are discussed. It has never been easier to accurately model viral molecular evolution, except that there are few suggestions or guidelines for how to conduct those analyses, and thus there is potential for garbage-in, garbage-out results that obfuscate the study of viral evolution.

3. The Evolution and Transmission of Vector-borne Viruses

Naomi L. Forrester, Serafín Gutiérrez and Lark L. Coffey

Arthropod-borne viruses or arboviruses are those that are transmitted between vertebrate or plant hosts by arthropod vectors such as mosquitoes, ticks or aphids. Here we discuss the implications of this particular life cycle on virus evolution and examine the different mechanisms by which these viruses have adapted to it. Different transmission strategies exist, some requiring replication within the vector and others not, and each strategy may impose different selection pressures and requires specific adaptations. We discuss the latest literature on the evolution of arboviruses at different scales (i.e. within-host and between-host evolution) and the strategies viruses have in countering the different barriers along their particular cycle, whether these barriers are anatomical barriers such as plant cell walls, or a host response such as an activated immune system. Finally we present the latest literature about how the viruses may affect the host and impact their behavior as well. The importance of understanding the evolution of these viruses particularly within the host cannot be understated as, any shift in host or adaptation to a marginal host can result in rapid expansion of the viruses.

4. Choose Your Weapons: Origins and Evolution of Innate Host Defenses and Viral Counterstrategies

Welkin E. Johnson

Viruses comprise the most abundant and genetically most diverse entities in the biosphere, and can be found in every environment and every niche occupied by cellular organisms. Viruses are common to all three domains of life, parasitizing the cells of eukaryotic, bacterial and archaeal hosts, and several lines of evidence suggest that viruses have been ever-present throughout the evolutionary history of modern, extant organisms. As a consequence of millions of years of virus-host coevolution, host organisms from all three domains have adapted by acquiring a variety of genes encoding dedicated antiviral effector mechanisms, and viruses, in turn, have evolved to encode an equally impressive array of accessory functions to counteract these defenses. Comparative approaches that draw on virus-host interactions from all three domains of life are beginning to reveal common macro-evolutionary processes by which these host and viral genes arise and evolve, and will hopefully lead to a fundamental understanding of how viruses influence host evolution (and vice versa).

5. Evolution of the Interactions of Viruses with Their Plant Hosts

Israel Pagán, Aurora Fraile and Fernando García-Arenal

More than a century of studies have shown that viruses are the causal agents of plant diseases. However, the vast majority of our understanding on plant-virus interactions derives from the study of viruses that cause diseases in crops. It has been only recently that scientists have started to explore plant-virus interactions in wild ecosystems. The results of these new studies have shown that in wild ecosystems plant viruses often appear to be commensals or even have beneficial effects for their hosts. Thus, the absence of negative effects of virus infection in wild ecosystems might be the rule, rather than the exception. This observation could change our perception of plant-virus interactions, and may lead to re-visiting our current understanding on how they evolve. Here, we review existing knowledge on three major aspects of the evolution of plant-virus interactions, plant-virus co-evolution, virus emergence and evolution of virus host range, with special attention to differences between wild and agricultural ecosystems.

6. Evolution of Viral Virulence: Empirical Studies

Gael Kurath and Andrew R. Wargo

The concept of virulence as a pathogen trait that can evolve in response to selection has led to a large body of virulence evolution theory developed in the 1980-1990s. Various aspects of this theory predict increased or decreased virulence in response to a complex array of selection pressures including mode of transmission, changes in host, mixed infection, vector-borne transmission, environmental changes, host vaccination, host resistance, and co-evolution of virus and host. A fundamental concept is prediction of trade-offs between the costs and benefits associated with higher virulence, leading to selection of optimal virulence levels. Through a combination of observational and experimental studies, including experimental evolution of viruses during serial passage, many of these predictions have now been explored in systems ranging from bacteriophage to viruses of plants, invertebrates, and vertebrate hosts. This chapter summarizes empirical studies of viral virulence evolution in numerous diverse systems, including the classic models myxomavirus in rabbits, Marek's disease virus in chickens, and HIV in humans. Collectively these studies support some aspects of virulence evolution theory, suggest modifications for other aspects, and show that predictions may apply in some virus:host interactions but not in others. Finally, we consider how virulence evolution theory applies to disease management in the field.

7. Taxonomy Advancement and Genome Size Change: Two Perspectives on RNA Virus Genetic Diversity

Chris Lauber and Alexander E. Gorbalenya

Relatively frequent insertion and deletion events, ranging from single nucleotides to full-length genes, and extreme point mutation rates make macroevolutionary studies of RNA viruses an exquisite challenge. Here we review recent advancements in the field concerning the study of both of these aspects and with regard to two specific applications - virus taxonomy and the analysis of genome size evolution. For the former we observe a dominant trend towards utilizing results from genetics-based virus classification during recent years. We also briefly discuss parallel developments for taxonomic studies of cellular organisms where very similar techniques are applied, but observe little cross-talk with virus taxonomy. For RNA virus genome size evolution we outline an emerging general pattern of genome (segment) enlargement being associated with a host- and mutation-constrained step-wise acquisition of key enzymes that seemingly improved the rudimentary RNA virus replication machinery. We discuss possible consequences for the upper limit on the size of the RNA virus genome segment currently observed for single-segment positive stranded nidoviruses.

8. Understanding Adaptation Through Experimental Evolution with Viruses: From Simple to Complex Environments

Valerie J. Morley and Paul E. Turner

A central goal of evolutionary biology is to better understand the processes that promote versus constrain adaptation in evolving populations; this aim is crucial for refining predictions on whether or not populations will successfully adapt to environmental change. Experimental evolution of viruses in controlled laboratory settings provides a powerful method for investigating generalized theories of adaptive evolution, and a vital approach for testing particular predictions on virus adaptive potential. Examples include the use of viruses to elucidate the dynamics of clonal interference between beneficial mutations vying to undergo fixation, the prevalence and character of epistatic interactions between genes, and the relative potencies of natural selection versus genetic drift in dictating evolutionary outcomes. While these efforts have helped refine predictions on adaptation occurring in constant environments, adaptation in complex or heterogeneous environments remains relatively seldom studied. Although organisms commonly encounter environments that are spatially and/or temporally complex, investigating the effects of environmental heterogeneity on evolution proves challenging in most study systems. Recent studies demonstrate that experimental evolution in viruses is a tractable and rigorous approach for resolving how evolution proceeds in heterogeneous environments. In this chapter, we review virus experiments that illuminate how basic evolutionary forces - especially selection, drift and migration - operate to dictate the fate of alleles and populations in simple and complex environments. We also suggest many exciting and open questions that remain to be explored using virus experimental models, such as empirical mapping of fitness landscapes, and the role of heterogeneous environments in promoting versus constraining virus adaptation.

9. Evolution of Persistent Viruses in Plants

Marilyn J. Roossinck

Persistent plant viruses have a unique natural history. They are cytoplasmic RNA viruses found in many plants, including many crop and ornamental plants, and are the most common type of virus found in wild plants. Persistent plant viruses have very long associations with their hosts. They do not move between plant cells, are found in every cell, and are only vertically transmitted. Their evolutionary history remains obscure but many aspects of their lifestyles imply mutualistic relationships with their plant hosts. Many are related to viruses of fungi, including endophytic fungi, and in some cases there is evidence for transmission between plants and fungi.

10. Paleovirology: The Study of Endogenous Viral Elements

Amr Aswad and Aris Katzourakis

Viruses sometimes heritably integrate into the genomes of their hosts, resulting in genomic features known as endogenous viral elements (EVEs). Using EVEs, the field of paleovirology investigates the long-term evolution of viruses and their impact on hosts. One of the fruitful outcomes of high throughput genomics is the widespread availability of whole genome data, offering the unprecedented opportunity to investigate EVEs at a large scale. In this chapter, we review the consequent surge in paleovirology research that can be traced to landmark work performed over half a century ago. We describe general principles of EVE biology and the main methodological techniques used to study them. We show how EVEs can only be understood within an evolutionary framework and we outline a generalized workflow for conducting paleovirology studies. We review exemplar paleovirological discoveries from each of the main viral groups, highlighting a range of approaches to paleovirology. We also discuss the major implications that certain discoveries and insights from paleovirology could have on our understanding of both virus and genome evolution. Finally, we consider the current limitations and potential pitfalls in paleovirology, and anticipate the possible future directions of this exciting and rapidly growing field.

11. Population Genetic Modeling of Viruses

Jayna Raghwani, Oliver G. Pybus and Chris J. R. Illingworth

Population genetics models provide a powerful approach to the study of the evolutionary dynamics of viruses. The application of population genetic approaches to viruses has grown in recent years and has been enabled by advances in sequencing technologies that make it feasible to obtain multiple 'genetic' snapshots of evolving viral populations through time. Populations of viruses are often shaped by a combination of high mutation rates, strong selection, large population sizes, and recurrent bottlenecks, and thus inhabit a different region of population genetic "parameter space" to cellular organisms. In this chapter, we discuss how traditional and novel population genetics models have provided insights into virus evolutionary processes and the means by which pathogenic viruses may be combatted. In particular, we illustrate how population genetics can be used to understand adaptive evolution in viruses and review recent work on whether viral evolution can be predicted.

12. Emerging Viral Infections

Michelle M. Becker, Everett Clinton Smith and Mark R. Denison

Viruses are small strands of nucleic acid housed within a shell of protein and sometimes lipid. For such minute particles, they capable of causing devastating effects on the health of humans and other inhabitants of this planet. Due to their large population sizes and short replication cycles, viruses evolve at an accelerated pace compared to larger organisms with longer life spans. This constant state of change allows them to continually sample sequence space and generate diverse populations containing viruses capable of transitioning into and adapting to a new host. When this happens, this virus may emerge in a naïve population and cause disease, in which case, we call the virus and the resultant disease emerging. Emerging infectious diseases (EIDs) appear to be increasing, which is likely the result of human intrusions into ecological niches, changes in vector distribution, altered climate patterns and other factors. In this chapter, we will highlight select animal and plant emergent viruses and review characteristics that have allowed these viruses to utilize the opportunities created by the changes listed above. We start with two viruses, Ebola and coronaviruses, that are currently epidemic. We also examine chikungunya, a virus with an expanding vector host and host range, and finish with parvoviruses and coffee ringspot virus, pathogens of domestic animals and an economically important crop, respectively.