However, studies have shown that upon acquisition of a first-step mutation, the likelihood of developing a subsequent mutation is enhanced in comparison to the development of the first-step mutation itself (38 – 40 ).
It was suggested that the probability of a secondary mutation is enhanced only by the increase in cell number within the developing colony and selection acts only to favor growth of the new double mutants within each colony.
The high incidence of mtDNA mutation in colorectal tissues of individuals with UC suggests that the rate of DNA mutation is enhanced in their mucosal cells by oxidative stress caused by chronic inflammation and, hence, malignant transformation occurs more easily than in normal subjects.
However, the 33% penetrant egg-laying defective (Egl) phenotype associated with the ksr-1 mutation was enhanced to 77% in the ndk-1 ok314 / ndk-1 ok314 / ksr-1(n2526) strain (n=125; Table 3).
Taking both observations together, the authors postulate the interesting idea that the high incidence of mtDNA mutations is enhanced in the mucosal cells of the patients with UC by a process of oxidative stress caused by the chronic inflammation.
In the intervention group, knowledge especially concerning inheritance and penetrance of BRCA1/2 mutations was enhanced (Table 3).
Specifically, the extraintestinal nuclei phenotypes resulting from ubc-25 (ok1732 ), lin-36 (n766 ), and cdc-14 (he141 ) mutations were enhanced by 15, 8, and 11 RNAi clones, respectively.
This pattern agrees quite well with the frequencies that optimal fit our models to the observed distributions, which are f(T) = 0.243, f(A) = 0.312, f(C) = 0.189, f(G) = 0.257 if the nucleotide frequencies are the only free parameters and detailed balance is assumed, and f(T) = 0.193, f(A) = 0.316, f(C) = 0.210, f(G) = 0.281 if the mutation rate is enhanced at CpG dinucleotides.
Through a greater neutral mutation rate, the chance that beneficial mutations might emerge is enhanced, therefore allowing neofunctionalization to occur faster, as has been proposed for the facilitation of morphological diversity in teleosts (Ravi and Venkatesh 2008).
We previously demonstrated that clinical isolates of S. aureus generally form a more robust biofilm than the 8325-4 laboratory strain RN6390 and that biofilm formation in the latter is enhanced by mutation of agr [10].
These findings suggest that the highly dense environment of mRNP granules facilitates fibril formation by the proteins noted above, especially when their aggregation propensity is enhanced by mutation.
