Darwin's Doubt: The Explosive Origin of Animal Life and the Case for Intelligent Design

by Stephen C. Meyer

The exon-shuffling hypothesis ignores the need for side-chain specificity, though the need for such specificity has repeatedly defeated attempts in the laboratory to build new proteins from units of secondary structure in the manner required. But advocates of exon shuffling make no attempt to show how random rearrangements of protein domains—whether the domains are conceived of as fragments of a fold or whole folds—would solve the combinatorial problem. Nor do they challenge Sauer’s or Axe’s experimentally derived quantitative estimates of the rarity of functional genes or proteins. They do not challenge the probability calculations based on these estimates. And they do not show that a mechanism exists that can search amino-acid sequence spaces more effectively or efficiently than random mutation and selection. Nor do they demonstrate the efficacy of exon shuffling in a model system in the laboratory. Instead, basic considerations of protein structure imply the implausibility of exon shuffling as a means of generating the genetic information necessary to produce a new protein fold.45 So, in the end, with few words and with apparent confidence, advocates of exon shuffling simply assert, as the Long paper does, that “exon shuffling often recombines sequences that encode various protein domains to create mosaic proteins.”