Large scale of human duplicate genes divergence.

Proteome complexity increases in the evolution mostly by means of gene duplication followed by divergence. In this genome-scale study of human genome I show that density distribution of duplicate gene pairs along the axis of protein divergence between pair members forms two main peaks with a small peak and plateau before the first main peak. This picture indicates the existence of three evolutionary stages of duplicate gene evolution. The analysis of various functional parameters (gene expression level and breadth, transcription factor targets, protein interaction networks) suggests that subfunctionalization (partition of function) is a predominant mode of divergence in the first main peak, whereas neofunctionalization (acquiring of novel functions) prevails in the second main peak. The young duplicate pairs show a much higher expression level compared with singleton genes and more diverged duplicates, which indicates that requirement for high gene dosage is important for retention of duplicates just after the duplication event. Thus, a prevailing route of duplicate evolution seems to be the high gene dosage-subfunctionalization-neofunctionalization. This adaptationist model suggests that an organism is evolving in the direction of its most intensively used functions.