Figure 2. Distinct evolutionary signatures for diverse classes of functional elements.

a, Protein-coding genes tolerate mutations that preserve the amino-acid translation, leading to abundant conservative codon substitutions (green). Insertions and deletions are largely constrained to be a multiple of three (grey). In contrast, non-coding regions show abundant non-conservative triplet substitutions (red), nonsense mutations (blue) and frame-shifting insertions and deletions (orange). b, RNA genes tolerate mutations that preserve the secondary structure (for example, single substitutions involving G•U base pairs and compensatory changes) and exclude structure-disrupting mutations. Matching parentheses and matching letters of the alphabet indicate paired bases. c, MicroRNA genes, in contrast, generally do not show changes in stem regions, but tolerate substitutions in loop regions and flanking unpaired regions, leading to a distinctive conservation profile. Asterisks denote the number of informant species matching the melanogaster sequence at each position. d, Regulatory motifs tolerate local movement and nucleotide substitutions consistent with their degeneracy patterns, and show increased conservation across the phylogenetic tree, measured as the branch length score (BLS; Supplementary Methods 5a). e, Increasing BLS thresholds select for instances of known motifs (black) at increasing confidence (red), as the number of conserved instances of control motifs (grey) drops significantly faster.