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Polymorphism Analysis Reveals Reduced Negative Selection and Elevated Rate of Insertions and Deletions in Intrinsically Disordered Protein Regions.

Khan T, Douglas GM, Patel P, Nguyen Ba AN, Moses AM - Genome Biol Evol (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell & Systems Biology, University of Toronto, Ontario, Canada.

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— Frequency of insertions/deletions per kilobase pair (Kb) indisordered regions, Pfam domains, other ordered regions, and noncoding DNAin S. cerevisiae and humans. (A) The number of indelpolymorphisms per Kb as a function of indel size for disordered regions(unfilled squares), other protein regions (gray squares), Pfam domains(filled squares) and Non-coding DNA (unfilled triangles).(B) Gray bars represent indels that were observed inmultiples of three (nonframeshifting indels). White bars represent indelsthat were not found as multiples of three (frameshifting indels). Thefrequency of frameshifting indels (Diso) in disordered regions is similar tothat of Pfam domains (Pfam). The frequency of nonframeshifting indels indisordered regions is similar to that of noncoding DNA (NonC), and muchhigher than the frequency of frameshifting indels. (C,D) Indels in the human genome display similar patternsas in yeast. (E) The fraction of out of frame indels islower in proteins than expected based on noncoding regions (dashed line),but is higher at the termini of proteins, consistent with reduced selectionon indels in the termini. This effect does not explain the differencebetween disordered regions (unfilled squares) and other protein regions(gray squares).
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evv105-F6: — Frequency of insertions/deletions per kilobase pair (Kb) indisordered regions, Pfam domains, other ordered regions, and noncoding DNAin S. cerevisiae and humans. (A) The number of indelpolymorphisms per Kb as a function of indel size for disordered regions(unfilled squares), other protein regions (gray squares), Pfam domains(filled squares) and Non-coding DNA (unfilled triangles).(B) Gray bars represent indels that were observed inmultiples of three (nonframeshifting indels). White bars represent indelsthat were not found as multiples of three (frameshifting indels). Thefrequency of frameshifting indels (Diso) in disordered regions is similar tothat of Pfam domains (Pfam). The frequency of nonframeshifting indels indisordered regions is similar to that of noncoding DNA (NonC), and muchhigher than the frequency of frameshifting indels. (C,D) Indels in the human genome display similar patternsas in yeast. (E) The fraction of out of frame indels islower in proteins than expected based on noncoding regions (dashed line),but is higher at the termini of proteins, consistent with reduced selectionon indels in the termini. This effect does not explain the differencebetween disordered regions (unfilled squares) and other protein regions(gray squares).

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.


Polymorphism Analysis Reveals Reduced Negative Selection and Elevated Rate of Insertions and Deletions in Intrinsically Disordered Protein Regions.

Khan T, Douglas GM, Patel P, Nguyen Ba AN, Moses AM - Genome Biol Evol (2015)

— Frequency of insertions/deletions per kilobase pair (Kb) indisordered regions, Pfam domains, other ordered regions, and noncoding DNAin S. cerevisiae and humans. (A) The number of indelpolymorphisms per Kb as a function of indel size for disordered regions(unfilled squares), other protein regions (gray squares), Pfam domains(filled squares) and Non-coding DNA (unfilled triangles).(B) Gray bars represent indels that were observed inmultiples of three (nonframeshifting indels). White bars represent indelsthat were not found as multiples of three (frameshifting indels). Thefrequency of frameshifting indels (Diso) in disordered regions is similar tothat of Pfam domains (Pfam). The frequency of nonframeshifting indels indisordered regions is similar to that of noncoding DNA (NonC), and muchhigher than the frequency of frameshifting indels. (C,D) Indels in the human genome display similar patternsas in yeast. (E) The fraction of out of frame indels islower in proteins than expected based on noncoding regions (dashed line),but is higher at the termini of proteins, consistent with reduced selectionon indels in the termini. This effect does not explain the differencebetween disordered regions (unfilled squares) and other protein regions(gray squares).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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evv105-F6: — Frequency of insertions/deletions per kilobase pair (Kb) indisordered regions, Pfam domains, other ordered regions, and noncoding DNAin S. cerevisiae and humans. (A) The number of indelpolymorphisms per Kb as a function of indel size for disordered regions(unfilled squares), other protein regions (gray squares), Pfam domains(filled squares) and Non-coding DNA (unfilled triangles).(B) Gray bars represent indels that were observed inmultiples of three (nonframeshifting indels). White bars represent indelsthat were not found as multiples of three (frameshifting indels). Thefrequency of frameshifting indels (Diso) in disordered regions is similar tothat of Pfam domains (Pfam). The frequency of nonframeshifting indels indisordered regions is similar to that of noncoding DNA (NonC), and muchhigher than the frequency of frameshifting indels. (C,D) Indels in the human genome display similar patternsas in yeast. (E) The fraction of out of frame indels islower in proteins than expected based on noncoding regions (dashed line),but is higher at the termini of proteins, consistent with reduced selectionon indels in the termini. This effect does not explain the differencebetween disordered regions (unfilled squares) and other protein regions(gray squares).
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell & Systems Biology, University of Toronto, Ontario, Canada.

Show MeSH