These mutations render all three PKA subunits sensitive to the small molecule 1-NM-PP1 (Bishop et al., 2000 ; Hao and O'Shea, 2012 ; Zaman et al., 2009 ).
Therefore, it is possible that co-existing mutations could render a therapeutic ineffective against an otherwise valid target.
Accumulation of unfavourable mutations may render a coding region nonfunctional, facilitating its removal from the genome in course of time.
In addition, particular oncogenic mutations may render a cell resistant to aging-associated insults, such as chronic inflammation that promotes cellular senescence or apoptosis due to increased reactive oxygen species (ROS) production.
On the other hand, IDH1/2 missense mutations render the enzymes acquiring neomorphic activity that can convert α-KG to 2-HG (Dang et al., 2009).
These mutations render the ras proteins insensitive to GTP-induced hydrolysis of GTP to GDP and lock them in the activated state [ 2, 8, 9].
There is emerging evidence that at least some culture-adaptive mutations render the strains more sensitive to antibody neutralization (Dhillon et al., 2010; Grove et al., 2008).
How many mutations would make an avian virus capable of infecting humans efficiently, or how many mutations would render an influenza virus a pandemic strain, is difficult to predict.
And while simple point mutations can render an antibody-based vaccine ineffective, cellular immune responses, considerably more promiscuous than their antibody counterpart, and can recognize several variants of the same epitope.
Conversely, if copies after single gene duplications or whole-genome duplication (WGD) are frequently lost, this may also indicate that even small mutations will easily render a protein nonfunctional.
