On the ancient nature of introns.

We discuss some of the arguments for introns arising early or late in evolution. We outline the exon theory of genes and discuss the series of discoveries of introns in the gene (TPI) encoding triosephosphate isomerase (TPI) that have filled out a series of better fits to the Go plot, culminating in the 1986 prediction of an intron position that was finally discovered in 1992. We present a statistical argument that the 11-intron structure of TPI (based on attributing all of the introns to an ancestral gene and interpreting three cases of very close intron positions as examples of sliding) has a clear relationship to the protein structure. The exons of this 11-intron TPI are a better approximation to Mitiko Go's modules (Go, 1981) than are 99.9% of all alternative exon patterns corresponding to 11 introns placed randomly in the gene, and better than 96% of all alternative patterns in which the lengths of the exons are preserved while the introns are moved. We combine four tests relating exons to protein structure: (i) whether the exons are compact modules, (ii) whether the exons contain most of the close contacts in the protein, (iii) whether the exon configuration maximized buried surface area along the backbone, and (iv) whether the exons maximize their content of hydrogen bonds. On a joint measure for these tests, the native exon structure with 11 introns fits these tests better than 99.4% of all alternative structures obtained by permuting the exon lengths and intron positions.(ABSTRACT TRUNCATED AT 250 WORDS)