This implies that during adaptation, populations move not only to a local fitness peak but also to a location in the sequence space that confers mutational robustness, such that single-nt mutations are less likely to result in unfit progeny.
PIK3R1 mutations are less common, although recently it was shown that PIK3R1 was mutated in up to 10% of glioblastomas (Cancer Genome Atlas Research Network, 2008; Parsons et al, 2008).
Among the most robust conclusions from these studies is that epistasis between beneficial mutations often shows a pattern of diminishing returns, in which favorable mutations are less fit when combined than would be expected.
In contrast, mutations within the tyrosine kinase domain of Flt3 (Flt3-TKD mutareons) are less frequent (approximately 7%), and there are only limited data on the frequency of recently demonstrated activating Flt3 point mutation at codon 592 Flt3-V592AA mutation).
Recessive mutations are less frequent, and many rare CMT forms still await genetic clarification.
A Ka/Ks ratio that is significantly less than 1 indicates that nonsynonymous mutations are less likely to become fixed in a population.
This approach is expected to establish a significant barrier against spontaneous viral escape from inhibition, since individual viral mutations are less likely to compensate for the loss of an essential host cofactor than to prevent high-affinity binding of a conventional, pathogen-directed antiviral.
Perhaps we see overall less variability in these regions because mutations are less tolerated.
Hereditary cancer syndromes resulting from ACVR1 loss-of-function mutations are less well known.
Therefore, these mutations are less sensitive to anti-Notch antibodies [ 30, 34].
BRCA1 mutations are less common in male than female breast cancer, and also affect prostate cancer (Liede et al, 2004).
