An earlier study with the bacterium P. fluorescens SBW25 and its lytic phage SBW25Φ2 (the same system as ours) showed that bacterial cultures with high mutation loads (caused by UV mutagenesis) had more rapid decline in relative fitness when coevolving with the phages during which multiple costly phage-resistance mutations should have accumulated (Buckling et al. 2006).
One could imagine that deep mutational scanning might enable more accurate assignment of the "mutational load" caused by specific mutations, although it remains unproven whether this would actually work.
This is an important aspect of influenza evolution, because traditional theory and data analysis of influenza evolution has focused on antigenic effects alone and neglected other evolutionary forces such as the genetic load caused by deleterious mutations.
If so, there would be indirect selection for large introns in regions of low recombination because they can reduce the load caused by deleterious mutations by increasing the recombination rate.
During the course of the experiment, a synergistic interaction is created between population size and the random effect of genetic drift, and this promotes the build up of the population mutation load which, in its extreme, causes a mutation meltdown and drives populations to extinction [ 19].
There are multiple mechanisms that could cause disease: a single point mutation that is clonally expanded throughout the cell, or a build up of random mutations (mutational load) that, having reached a threshold, causes the onset of disease.
The most severe mtDNA mutations are deletions, which cause respiratory dysfunction at a lower mutation load than point mutations (reviewed in [ 1]).
Once the deleterious mutation load has largely been shed, the reassortant virus would quickly rise and cause an antigenic cluster transition.
Therefore it is expected that the reversible polyploidy caused by anti-cancer drugs should elicit mechanisms which mitigate aneuploidy, reduce mutation load and the associated genotoxic/metabolic stress, thus favoring cell fitness for tumor progression and treatment resistance.
Returning to our model, given that an antigenic mutation arises in a strain carrying some deleterious mutation load, one might expect the virus population's deleterious mutation load to increase in the long run, causing a long-term decline in influenza A/H3N2 fitness.
