Exons--original building blocks of proteins?

In a recent paper, Walter Gilbert's group has estimated the number of original exons from which all extant proteins might have been constructed. The approach used is subjected to a critical analysis here. It is shown that there are flawed assumptions about both the mechanism and generality of exon-shuffling and in the sequence comparison procedures employed, the latter failing to distinguish chance similarity from similarity due to common ancestry. These methodological errors lead to the omission of many known cases of exon-shuffling and the inclusion of others which may not be genuine. In consequence, the analysis from the Gilbert group cannot give a reliable estimate of those modules that actually participated in exon-shuffling and provides no information on the number of protein archetypes that did not participate in these processes.