The existence of 4/8-fold internal symmetry was suggested based on a computational analysis of TIM barrel sequences. For example, "Escherichia coli" KDPG aldolase () was suggested to possess a distinct 4-fold symmetry, with discernible 8-fold symmetry. The design of a 4-fold symmetric TIM barrel confirmed the possibility of higher orders of internal symmetry in natural TIM barrels, and will be discussed in detail in the next section. No experimental evidence for the existence of 8-fold symmetric TIM barrels has been reported to date.