Centripetal modules and ancient introns

We have created an algorithm which instantiates the centripetal definition of modules, compact regions of protein structure, as introduced by Go and N osaka (M. Go and M. Nosaka, 1987. Protein architecture and the origin of in trons. Cold Spring Harbor Symp. Quant. Bio. 52, 915-924). That definition s eeks the minima of a function that sums the squares of C-alpha-carbon dista nces over a window around each amino acid residue in a three-dimensional pr otein structure and identifies such minima with module boundaries. We analy ze a set of 44 ancient conserved proteins, with known three-dimensional str uctures, which have intronless homologues in bacteria and intron-containing homologues in the eukaryotes, with a corresponding set of 988 intron posit ions. We show that the phase zero intron positions are significantly correl ated with the module boundaries (p=0.0002), while the intron positions that lie within codons, in phase one and phase two, are not correlated with the se 'centripetal' module boundaries. Furthermore, we analyze the phylogenetic distribution of intron positions a nd identify a subset of putatively 'ancient' intron positions: phase zero p ositions in one phylogenetic kingdom which have an associated intron either in an identical position or within three codons in another phylogenetic ki ngdom (a notion of intron sliding). This subset of 120 'ancient' introns li es closer to the module boundaries than does the full set of phase zero int rons with high significance, a p-value of 0.008. We conclude that the behav ior of this set of introns supports the prediction of a mixed theory: that some introns are very old and were used for exon shuffling in the progenote , while many introns have been lost and added since. (C) 1999 Elsevier Scie nce B.V. All rights reserved.