Simple repeat evolution includes dramatic primary sequence changes that conserve folding potential

We previously demonstrated that many “weak-folding” simple repeats were replaced during evolution by alternative weak-folding repeats. This suggested repeat selection at the level of higher order structure potential. Here, we demonstrate similar phenomena for “strong-folding” simple repeats in non-coding DNA. The Rabgap1 gene's 3′ UTR contained the self-complementary repeat (AT)n in Homo sapiens but, in Mus musculus, this site was occupied by the complementary repeats (GT)n and (AC)n. Similarly, primate Plag1 UTRs contained various (GT)n-(AC)n palindromes but in rodents, this site was occupied by (AT)n, preserving folding potential more than primary sequence. The Znf516, Senp1, Rock2, and other UTRs exhibited similar replacements. In the Bnc2 UTR, (AT)n was replaced by sequences that evolved with approximate symmetry about a central axis, a pattern difficult to explain without invoking selection to preserve secondary structure. These observations reflect a predictable evolutionary pattern for some common non-coding genomic sequences.