The participant believes that mutations cannot be constructive (useful).
When chaperone becomes scarce, either because of increased need due to stress or due to a mutation in a chaperone, the accumulated destabilizing mutations cannot be buffered and the malfunctioning of proteins manifests in the mutant phenotype.
In addition, understanding the epigenetic mechanisms that underlie these alterations has also provided new therapeutic potential, even if the driver mutations cannot be targeted directly (e.g. HDACi, DNMT inhibitors) (Table 1) (Arrowsmith et al., 2012; Foulks et al., 2012; Helin and Dhanak, 2013; New et al., 2012; Plass et al., 2013).
Although most of these mutations cannot be prevented, the team stressed that early detection and treatment can prevent many cancer deaths, regardless of the cause.
A secondary role of mtDNA mutations cannot be fully ruled out under the hypothesis that the progressive accumulation of mtDNA instabilities could finally contribute to the tumoral process.
As these mutations cannot be as easily recognized as non-synonymous mutations there is always the risk that they remain unidentified.
While some aspects are in line with balancing selection, parallel directional positive selection favouring all slow causing mutations cannot be ruled out, as was first proposed by Patin et al. [8] when considering the *5 series alone.
The clinical significance of these unrecognized mutations cannot be ascertained due to the cross-sectional nature of our study; however, we can conclude that the majority of unrecognized resistant mutations correlate with historical antiretroviral use rather than to the failing antiretroviral drugs.
By contrast, all tRNAs cognate for NNC can also read NNU [33], [50], irrespective of whether the tRNA wobble base is G or I. Therefore, any improvement in translation resulting from the 47% U to C mutations cannot be due to differential tRNA concentrations, but must be due to a greater efficacy of the tRNA in reading NNC as opposed to NNU.
Although the clinical significance of these unrecognized mutations cannot be ascertained due to the cross-sectional nature of our study, a potential clinical implication here is that conventional genotype might be adequate for a subset of patients with well-characterized antiretroviral treatment histories and known longitudinal HIV genotypes.
Those mutations cannot be detected with focus techniques.
