Rapid subfunctionalization accompanied by prolonged and substantial neofunctionalization in duplicate gene evolution

Gene duplication is the primary source of new genes. Duplicate genes that are stably preserved in genomes usually have divergent functions. The general rules governing the functional divergence, however, are not well understood and are controversial. The neofunctionalization (NF) hypothesis asserts that after duplication one daughter gene retains the ancestral function while the other acquires new functions. In contrast, the subfunctionalization (SF) hypothesis argues that duplicate genes experience degenerate mutations that reduce their joint levels and patterns of activity to that of the single ancestral gene. We here show that neither NF nor SF alone adequately explains the genome-wide patterns of yeast protein interaction and human gene expression for duplicate genes. Instead, our analysis reveals rapid SF, accompanied by prolonged and substantial NF in a large proportion of duplicate genes, suggesting a new model termed subneofunctionalization (SNF). Our results demonstrate that enormous numbers of new functions have originated via gene duplication.