Mutational Robustness and Asymmetric Functional Specialization of Duplicate Genes

Most duplicate genes are eliminated from a genome shortly after duplication, but those that remain are an important source of biochemical diversity. Much of their diversification arises via functional “specialization,” loss of some functions of the duplicates remaining in the genome. I here present evidence from genome-scale protein-protein interaction data, microarray expression data, and large-scale gene knockout data that this diversification is often asymmetrical: one duplicate usually shows significantly more molecular or genetic interactions than the other. I propose a model that can explain this divergence pattern if duplicate gene pairs are less likely to suffer deleterious mutations when having diverged asymmetrically. The data may provide the first evidence that natural selection has increased mutational robustness in genetic networks.