The evolution of protein sequences by repetitious gene duplication: Clostridial flavodoxin

Summary Internal regularities of amino acid sequences of flavodoxins, FMN-containing, low molecular weight flavoproteins, were statistically examined using the minimum mutation method. The sequence ofClostridium pasteurianum flavodoxin shows statistically significant evidence of repetitious internal gene duplications at different levels of structure. Peptide pairs with a low chance probability of occurrence were frequently observed at a shift of 5 residues. The pairs with the lowest chance probabilites are a pair of heptapeptides at positions 39–45 vs. 44–50, a 5 residue shift (p = 9 × 10^–6). Most of the related pairs are consistent and could best be explained by the repeating pentapeptide sequence: (Lys-Gly-Ala-Asp-Val-)_n and appropriate gaps. Internal repetitions with longer shifts were also suggested for other flavodoxins. Repetitious gene duplication is proposed for the early stages of flavodoxin evolution.