A tendency for exons to correspond to discrete units of protein struct
ure in protein-coding genes of ancient origin would provide clear evid
ence in favor of the exon theory of genes, which proposes that split g
enes arose not by insertion of introns into unsplit genes, but from co
mbinations of primordial mini-genes (exons) separated by spacers (intr
ons). Although putative examples of such correspondence have strongly
influenced previous debate on the origin of introns, a general corresp
ondence has not been rigorously proved. Objective methods for detectin
g correspondences were developed and applied to four examples that hav
e been cited previously as evidence of the exon theory of genes. No si
gnificant correspondence between exons and units of protein structure
was detected, suggesting that the putative correspondence does not exi
st and that the exon theory of genes is untenable.