Abstract
The attenuation of myxoma virus (MYXV) following its introduction as a biological control into the European rabbit populations of Australia and Europe is the canonical study of the evolution of virulence. However, the evolutionary genetics of this profound change in host-pathogen relationship is unknown. We describe the genome-scale evolution of MYXV covering a range of virulence grades sampled over 49 years from the parallel Australian and European epidemics, including the high-virulence progenitor strains released in the early 1950s. MYXV evolved rapidly over the sampling period, exhibiting one of the highest nucleotide substitution rates ever reported for a double-stranded DNA virus, and indicative of a relatively high mutation rate and/or a continually changing selective environment. Our comparative sequence data reveal that changes in virulence involved multiple genes, likely losses of gene function due to insertion-deletion events, and no mutations common to specific virulence grades. Hence, despite the similarity in selection pressures there are multiple genetic routes to attain either highly virulent or attenuated phenotypes in MYXV, resulting in convergence for phenotype but not genotype.
Highlights
The classic model of pathogen evolution following a species jump is the introduction of the lethal myxoma virus (Poxviridae, genus Leporipoxvirus) into the European rabbit (Oryctolagus cuniculus) populations of Australia as a biological control [1]
The text-book example of the evolution of virulence is the attenuation of myxoma virus (MYXV) following its introduction as a biological control into the European rabbit populations of Australia and Europe in the 1950s
By sequencing and comparing MYXV genomes, including the original strains released in the 1950s, we show that (i) MYXV evolved rapidly in both Australia and Europe, producing one of the highest rates of evolutionary change ever recorded for a DNA virus, (ii) that changes in virulence were caused by mutations in multiple genes, often involving losses of gene function due to insertions and deletions, and that (iii) strains of the same virulence were defined by different mutations, such that both attenuated and virulent MYXV strains are produced by a variety genetic pathways, and generating convergent evolution for phenotype but not genotype
Summary
The classic model of pathogen evolution following a species jump is the introduction of the lethal myxoma virus (Poxviridae, genus Leporipoxvirus) into the European rabbit (Oryctolagus cuniculus) populations of Australia as a biological control [1]. Within two years of the introduction of SLS, and despite the ongoing release of virulent viruses, slightly attenuated MYXV strains came to dominate field populations They still killed 90–99% of infected rabbits, these lower virulence strains allowed infected rabbits to survive for longer, increasing the probability of transmission from skin lesions by mosquito vectors [2,3]. Natural selection acted on the wild rabbit population, resulting in the emergence of animals resistant to myxomatosis [6,7], likely through an enhanced innate immune response [8,9] This effectively reduced the virulence of field strains of MYXV in wild compared to laboratory rabbits. The evolutionary outcomes were strikingly similar to those in Australia, with the emergence of attenuated virus strains and selection for resistant rabbits [1]
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