Download 27. The micro-evolution of FMDV

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: [email protected]
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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