Preservation of duplicate genes by complementary, degenerative mutations

The origin of organismal complexity is generally thought to be tightly coup led to the evolution of new gene functions arising subsequent to gene dupli cation. Under the classical model for the evolution of duplicate genes, one member of the duplicated pair usually degenerates within a few million yea rs by accumulating deleterious mutations, while the other duplicate retains the original function. This model further predicts that on rare occasions, one duplicate may acquire a new adaptive function, resulting in the preser vation of both members of the pair, one with the new function and the other retaining the old. However, empirical data suggest that a much greater pro portion of gene duplicates is preserved than predicted by the classical mod el. Here we present a new conceptual framework for understanding the evolut ion of duplicate genes that may help explain this conundrum. Focusing on th e regulatory complexity of eukaryotic genes, ive show how complementary deg enerative mutations in different regulatory elements of duplicated genes ca n facilitate the preservation of both duplicates, thereby increasing long-t erm opportunities for the evolution of new gene functions. The duplication- degeneration-complementation (DDC) model predicts that (1) degenerative mut ations in regulatory elements can increase rather than reduce the probabili ty of duplicate gene preservation and (2) the usual mechanism of duplicate gene preservation is the partitioning of ancestral functions rather than th e evolution of new functions. We present several examples (including analys is of a new en,engrailed gene in zebrafish) that appear to be consistent wi th the DDC model, and we suggest several analytical and experimental approa ches for determining whether the complementary loss of gene subfunctions or the acquisition of novel functions are likely to be the primary mechanisms for the preservation of gene duplicates.