Appendix 27 Outstanding but tractable questions regarding the micro-evolution of FMDV Daniel T Haydon Division of Environmental and Evolutionary Biology, University of Glasgow, Glasgow G12 8QQ E-mail: D.Haydon@bio.gla.ac.uk Our knowledge of fundamental processes underlying the population genetics of FMDV remains far from complete. Whether or not the dynamics of viral populations within individuals are governed by the principles of ‘quasi-species’ or those of more conventional ‘Darwinian’ selection depends critically on both the mutation rate and the intensity and scale of epistasis within the viral genome. Uncertainty in current estimates of RNA virus mutation rate are such that neither mode of evolution can be ruled out. High levels of epistasis will increase the role for quasi-species dynamics in the ‘within-individual’ evolution of FMDV but we know next to nothing about either the intensity or genomic scale of epistasis. Evidence is accumulating that recombination rates may be sufficiently high that recombinant genomes could pose a significant source of antigenic novelty – the threat of such recombinants arising will increase with the frequency that multiple strains and serotypes cocirculate within a region. Simple and plausible models of FMDV population genetics suggest that virus excreted by an infected animal might on average differ by 1 nucleotide mutation to its capsid genes from the virus with which an individual was infected. If this were true – and there are many interesting reasons why it might not be – it suggests that genetic characterization could be used to trace transmission events at much higher resolutions than is routinely attempted, and there is increasing empirical evidence to suggest this to be the case. Ultimately we need to link genetic diversity more explicitly and directly to antigenic characteristics. This will require advances in three areas: higher resolution, and more accurate and widespread comparisons of the antigenicity of the FMDV capsid, more complete capsid sequences from field and vaccine stains, and computational algorithms that can map between these two sources of information.
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