INTRON POSITIONS CORRELATE WITH MODULE BOUNDARIES IN ANCIENT PROTEINS

We analyze the three-dimensional structure of proteins by a computer p rogram that finds regions of sequence that contain module boundaries, defining a module as a segment of pol peptide chain bounded in space b y a specific given distance, The program defines a set of ''linker reg ions'' that have the property that if an intron were to be placed into each linker region, the protein would be dissected into a set of modu les all less than the specified diameter. We test a set of 32 proteins , all of ancient origin, and a corresponding set of 570 intron positio ns, to ask if there is a statistically significant excess of intron po sitions within the linker regions. For 28-Angstrom modules, a standard size used historically, we find such an excess, with P < 0.003. This correlation is neither due to a compositional or sequence bias in the linker regions nor to a surface bias in intron positions, Furthermore, a subset of 20 introns, which can be putatively identified as old, li es even more explicitly within the linker regions, with P < 0.0003, Th us, there is a strong correlation between intron positions and three-d imensional structural elements of ancient proteins as expected by the introns-early approach, We then study a range of module diameters and show that, as the diameter varies, significant peaks of correlation ap pear for module diameters centered at 21.7, 27.6, and 32.9 Angstrom. T hese preferred module diameters roughly correspond to predicted exon s izes of 15, 22, and 30 residues, Thus, there are significant correlati ons between introns, modules, and a quantized pattern of the lengths o f polypeptide chains, which is the prediction of the ''Exon Theory of Genes.''