Phylogenetic trees are the most widespread presentation for viral phylogenies in the literature. Several tree-building methods and software tools exist (e.g. MrBayes, RAxML), but these methods produce incorrect results for viral phylogenies due to the complex evolutionary relationships that are relevant for viruses, such as horizontal gene transfer, intra- or interspecific recombination, positive selection, or the evolutionary relationships between viruses and their hosts. There is a clear need for specialised computational methods to support the reconstruction of these special aspects of virus phylogeny. In this work package, VIROINF finally combines the results of all ESR to contribute to the macroevolution of viruses.
Existing phylogenetic methods assume that distinct sites within the genome evolve independently, which results in severe errors when evolution is driven by epistatic constraints. ESR 8 will infer the evolutionary linkages between distinct genomic sites in order to develop methods to accurately reconstruct viral phylogenies in the presence of disruptive processes such as virus recombination. The necessary genotypic data for this task will be derived from controlled evolution experiments carried out by ESR 4, who will serially passage single and mixed viral genotypes (DWV-A and -B) in vivo (in the honeybee) to investigate the role of recombination in virus adaptation. The honeybee is a key model in environmental research and agriculture and the ESR 4 in this project will characterise how DWV evolves to exploit the honeybee host to increase virus replication, with a focus on characterising host transcriptome targets, including RNAi machinery and the Toll immune pathway (e.g. the key gene regulator dorsal). Virus phenotypic measures will include virus growth and virulence (host mortality) and will be matched against in-depth virus population sequencing in order to facilitate genotype-phenotype mapping with ESR 8 (see WP 2.1). For large evolutionary distances, it is possible to infer phylogenies based on comparative analyses of macromolecular structures, which evolve much slower than sequences. This approach will be used by ESR 7 and ESR 14 to compute phages serving as specific treatments against harmful bacteria.