By design, our analysis has focused on mutations with very large fitness effects.
If colony fitness increases due to increased worker-worker interactions, selection on mutations with indirect effects on workers can be substantial.
Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems.
Incomplete penetrance under all the tested conditions suggests that this phase may use highly redundant pathways, involve novel mechanisms, or depend on mutations with lethal phenotypes.
According to the FGM, events of selection are more likely to be observed on mutations with small phenotypic effects (following a geometric distribution), whereas positive selection on mutations with large effects is most likely to occur during the first steps of adaptation.
In this study, we further tested the computational structural model on mutations with known effect on receptor-binding properties (2, 3, 6 – 9 ) in H5N1 context based on recently resolved crystal structures and the respective ligand complexes (9 ).
Similar to scenario 2, selection on mutations with indirect genetic effects on worker behavior will increase linkage disequilibrium and interference selection, which in turn can select for the evolution of higher recombination rates.
Also, it applies across any magnitude of bias, e.g., the dramatic reversals that we imagined previously are merely kinetically disfavored pathways, by virtue of relying on mutations with exceedingly low rates.
Systems biology has accumulated much data on mutations with relatively large effects by using experimental methods and theoretical tools like flux balance analysis, which analyses the flux of metabolites in biochemical reaction networks [ 3- 12].
