However, little evidence has been found for the existence of an ancestral half-barrel in the evolution of other 8-barrel proteins.
In order to detect remnants of an ancestral half-barrel in the 8-barrel structure of Escherichia coli N- 5′-phosphoribosyl)aN- 5′-phosphoribosyle, we eN- 5′-phosphoribosylntianthranilateel unisomerase 3–6, and 5–8.
According to the model proposed, the first duplication involved an ancestral module (half the size of the present-day hisA gene) and led by a gene elongation event to the ancestral hisA gene which, in turn, underwent a duplication that gave rise to the hisF gene (Fig. 11).
Comparison of these modules led to the suggestion that hisA and hisF are the result of two ancient successive duplications, the first one involving an ancestral module half the size of the present-day hisA gene and leading (by a gene elongation event) to the ancestral hisA gene, which in turn underwent a duplication that gave rise to the ancestor of hisF [ 18].
It has been postulated that the ubiquitous 8-barrel enzyme fold has evolved by duplication and fusion of an ancestral 4-half-barrel.
These results are in agreement with the hypothesis about common origin of all 8-barrel protein domains, that evolved from an ancestral 4 half-barrel by a tandem gene duplication followed by a fusion [ 55- 60].
According to the model proposed [ 18, 19] the ancestral half-barrel gave a functional enzyme by homo-dimerization.
The possibility of an even older gene-elongation event involving -mers smaller than the 4 units of the ancestral "half-barrel" precursor was recently investigated (Fani et al. 2007) by an extensive analysis of all the available HisA and HisF sequences.
It has been assumed that the HIV peptidase represents the ancestral state and that the ancestral half-pepsin also had to dimerize to be active.
The structural symmetry of the TIM barrel has prompted us to investigate the possibility of an even older gene elongation event involving -mers smaller than the 4 units of the ancestral "half-barrel" precursor.
As previously mentioned all MIPs have an internal symmetry believed to derive from a duplication of an ancestral gene encoding only half of the present MIP sequence.
