For these mutations, we change the base pair positions in which the mutation occurred as follows: we randomly sample the base pair positions from the base pair positions within the sequence of all genes, which correspond to the same base pair types as the mutations.
To see the effect of variation of mutation rates across samples, we change the sample ID in which mutations occurred by sampling a new sample ID under two different distributions namely, moderate sample variation and high sample variation.
Therefore, in the absence of new mutations, we expect a change in the rate of response to selection.
The nonsense mutation we discovered changes a cytosine to an adenine in exon 3 of fugu Mstn converting a tyrosine codon to a stop codon in a fry from the family 4.
To apply a further test to the idea that the conductive conformation of the pore is stabilized by the I148T/L267P and W275S GOF mutations, we measured how pHO changes affected the ion selectivity of the mutants in comparison with wild-type K2P2.1 (TREK-1).
Importantly, considering that missense mutations do not necessarily change protein function as severely as nonsense or frameshift mutations, we primarily focused on base changes resulting in premature stop codons and indels within coding exons.
By isolating individual mutations, we identified specific amino acid changes that dramatically improved discrimination.
For all positions, the cap mutations changed Keq mainly by changing ko (resulting in high Φ values).
The discovery of driver mutations and drugs targeting these mutations has changed the treatment landscape.
As non-sense mutations probably change protein function, we category them as functional variants, and assign them the highest quantitative weight among others.
