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: To determine the relative importance of natural selection in driving amino acidalterations within eukaryotic proteins, we determined the ratio of nonsynonymous(amino acid changing) to synonymous polymorphisms(Pa/Ps) in the S.cerevisiae genome and observedPa/Ps values of 0.24,0.090, and 0.13 for disordered regions, Pfam domains, and other ordered regions,respectively (fig. 2A).We also determined Pa/Psratios and indel polymorphism rates in humans, using data from the 1000 genomesproject (1000 Genomes Project Consortium2012). The Pa/Psratios in disordered regions, Pfam domains, and other ordered regions were 0.48,0.36, and 0.40, respectively (fig.1A). As expected, disordered regions had the highestPa/Ps ratio, while Pfamdomains showed the lowest value, a trend that is consistent with our findings in theS. cerevisiae genome. Because all these ratios are much lowerthan 1, it can be inferred that all three regions are under strong negativeselection, albeit weaker in disordered regions relative to structured proteinregions. To get a sense of the variability, we also computed these ratios for eachgene and plotted the distribution (fig.1B). The results were consistent with the pooled resultabove. Fig. 2.
Affiliation: Department of Cell & Systems Biology, University of Toronto, Ontario, Canada.