The D320E mutation, when combined with R318W, either with or without [A241P + R262Q], resulted in a phenotype that was about 10-fold less sensitive to CsA (Figure 3E).
These data are consistent with the notion that the T790M mutation, when combined with activating EGFR kinase domain mutations, confers enhanced catalytic phosphorylating activity, as shown by others using insect cells infected with baculovirus expressing various EGFR intracellular domain constructs [19].
As the number of substitutions increases on each lineage, we can see that each lineage will maintain good fitness in a stabilizing landscape through compensatory changes, which each try to minimize the number of mismatches; however, each lineage fixes different sets of compensatory mutations, so when combined in a hybrid, the epistasis between pairs of sequences then gives rise to DMIs.
Application of this method allows for identification of gains and losses in targeted sequence data, providing comprehensive mutation screening when combined with a short read aligner.
Specifically, null mutations in halA, when combined with null mutations in sltA, result in an elevated requirement for calcium.
Co-lethality, or synthetic lethality is the documented genetic situation where two, separately non-lethal mutations, become lethal when combined in one genome.
One remarkable result of these synthetic lethal interactions is that neither the SA nor the SE mutation is lethal when combined with dyn1Δ or kar9Δ deletions (Table 2).
We found that the poor reactivity of the N36C mutation was retained when combined with the improved N-terminal sequence (ESI, † Fig. S7 S9).
In contrast to spt10 Δ, an spt21 Δ mutation allowed viability when combined with hir1 Δ or asf1 Δ (Table 6).
Second, the high mitotic index caused by the asp mutation is strongly reduced when combined with cenp-metaΔ mutation, thereby suggesting that somehow Cenp-meta helps to maintain the SAC intensity or duration.
