Insertion/deletion and nucleotide polymorphism data reveal constraints in Drosophila melanogaster introns and intergenic regions

Abstract

Our study of nucleotide sequence and insertion/deletion polymorphism in Drosophila melanogaster noncoding DNA provides evidence for selective pressures in both intergenic regions and introns (of the large size class). Intronic and intergenic sequences show a similar polymorphic deletion bias. Insertions have smaller sizes and higher frequencies than deletions, supporting the hypothesis that insertions are selected to compensate for the loss of DNA caused by deletion bias. Analysis of a simple model of selective constraints suggests that the blocks of functional elements located in intergenic sequences are on average larger than those in introns, while the length distribution of relatively unconstrained sequences interspaced between these blocks is similar in intronic and intergenic regions.

Figure 1.—

Schematic of the model of selective constraints considered in the analysis. Subsequences are delimited by blocks (shaded boxes) of coding (exons) or noncoding functional DNA (e.g., regulatory regions or splicing elements). Deletions (solid triangles) are deleterious when they overlap with constrained blocks (crossed-out triangles), while both insertions (open triangles) and deletions may be subjected to purifying selection if they alter spacing constraints (i.e., length of subsequence).

Figure 2.—

Size distribution of insertions (solid bars) and deletions (shaded bars) in (A) introns and (B) intergenic regions. The solid portions correspond to nonrepetitive indels.

Figure 3.—

Modeling the insertion and deletion profile in the presence of varying functional constraints. (A) Theoretical results for the fraction of insertions (ins) and deletions (del) ≤10 bp and the polymorphic deletion bias (PDB). (B) Fraction of insertion (n-ins), deletion (n-del), and deletion and total indel (n-indel) events that do not alter functional DNA blocks and spacing constraints. We assume that under neutrality the ratio of deletions to insertions is 6:1 and that there are equal size distributions for insertions and deletions (Petrov and Hartl 1998; Blumenstiel et al. 2002). The short and long subsequences have lengths of 30 and 200 bp, respectively, and are subjected to relaxed (rel) or strong (str) spacing constraints (see text for details).