Polymorphism Analysis Reveals Reduced Negative Selection and Elevated Rate of Insertions and Deletions in Intrinsically Disordered Protein Regions.
Bottom Line: We also confirm previous findings that nonframeshifting indels are much more abundant in disordered regions relative to structured regions.We find that the rate of nonframeshifting indel polymorphism in intrinsically disordered regions resembles that of noncoding DNA and pseudogenes, and that large indels segregate in disordered regions in the human population.Our survey of polymorphism confirms patterns of evolution in disordered regions inferred based on longer evolutionary comparisons.
Affiliation: Department of Cell & Systems Biology, University of Toronto, Ontario, Canada.Show MeSH
Mentions: We sought to test whether the efficacy of selection to retain the biochemical type ofamino acid was similar in ordered regions and disordered regions. To do so, wecomputed the fraction of the total nearly neutral sites(Nes < 1) that change thebiochemical type. For example, is the fraction of neutral biochemically changingsites for the “O” residues. In defining this fraction,FO→D, we are controlling for the total numberof neutral sites, which we found above to be higher in disordered regions (fig. 4). We find that the fraction ofneutral biochemically changing sites is higher in disordered regions than in othermore structured regions (both FO→D, fig. 6A, andFD→O, fig. 6B; Wilcoxon test, P <10−6). This confirms that negative selection acts topreserve these biochemical types of residues more strongly within ordered regions, asopposed to simply being stronger proportionately over all residues.
Affiliation: Department of Cell & Systems Biology, University of Toronto, Ontario, Canada.