Gauging genetic diversity of generalists: A test of genetic and ecological generalism with RNA virus experimental evolution

Generalist viruses, those with a comparatively larger host range, are considered more likely to emerge on new hosts. The potential to emerge in new hosts has been linked to viral genetic diversity, a measure of evolvability. However, there is no consensus on whether infecting a larger number of hosts leads to higher genetic diversity, or whether diversity is better maintained in a homogeneous environment, similar to the lifestyle of a specialist virus. Using experimental evolution with the RNA bacteriophage phi6, we directly tested whether genetic generalism (carrying an expanded host range mutation) or environmental generalism (growing on heterogeneous hosts) leads to viral populations with more genetic variation. Sixteen evolved viral lineages were deep sequenced to provide genetic evidence for population diversity. When evolved on a single host, specialist and generalist genotypes both maintained the same level of diversity (measured by the number of single nucleotide polymorphisms (SNPs) above 1%, P = 0.81). However, the generalist genotype evolved on a single host had higher SNP levels than generalist lineages under two heterogeneous host passaging schemes (P = 0.001, P < 0.001). RNA viruses’ response to selection in alternating hosts reduces standing genetic diversity compared to those evolving in a single host to which the virus is already well-adapted.