Pleiotropy seems to act at the gene-level for the deletion collection and at a mutation-level for the recombinant population.
For the respective mutations' levels of penetrance (e in males and d in females) we chose values from the entire meaningful range.
It would appear that regenerating muscle cells are subjected to two periods of selection, with the first phase occurring very early on before myoblasts were assessed for mutation levels.
Despite the potential for high viral mutation levels, the operation of purifying selection appears to effectively constrain lyssavirus evolution.
A second comparison group for day 0 mutation levels was derived from a Phase I trial of KP1461 (Clay et al, manuscript in preparation) (Figure 3B, rightmost column), who, like the Phase IIa trial participants, had more advanced infection.
Given its clear link with PD, a variety of SNCA transgenic mice have been generated, varying in tissue specificity, mutation and expression level (for a review see Fernagut & Chesselet 2004).
Because mutation-level pleiotropy is more relevant for evolutionary history (Paaby and Rockman 2014), a greater prevalence of AP in recombinant population compared with the deletion collection indicates that AP plays a role in adaptation.
The irrE mutants obtained in this study were sequenced, and the mutations are summarized at both the primary sequence level (for all mutations), and at the homology model level (for mutations within the range of residues 44 303), shown in Figure 9A and Figure 9B.
It therefore has no effect on the conclusion that the strength of selection is approximately proportional to the expression level for mutations with small effect.
Focusing on the regulatory level for mutations in this way is justified by recent work recognizing the overwhelming relative importance of regulatory divergence in paralog gene evolution [ 23].
In addition to being a major source of variation, mutation may also function as a mechanism of evolution when there are different probabilities at the molecular level for different mutations to occur, a process known as mutation bias.
