Rapid and asymmetric divergence of duplicate genes in the human gene coexpression network

Here we build a human gene coexpression network using human tissue-specific microarray data and investigate the divergence of duplicate genes in it. The topology of this network is scale-free. Interestingly, our analysis indicates that duplicate genes rapidly lose shared coexpressed partners: after approximately 50 million years since duplication, the two duplicate genes in a pair have only slightly higher number of shared partners as compared with two random singletons. We also show that duplicate gene pairs quickly acquire new coexpressed partners: the average number of partners for a duplicate gene pair is significantly greater than that for a singleton (the latter number can be used as a proxy of the number of partners for a parental singleton gene before duplication). The divergence in gene expression between two duplicates in a pair occurs asymmetrically: one gene usually has more partners than the other one. The network is resilient to both random and degree-based in silico removal of either singletons or duplicate genes. In contrast, the network is especially vulnerable to the removal of highly connected genes when duplicate genes and singletons are considered together.Duplicate genes rapidly diverge in their expression profiles in the network and play similar role in maintaining the network robustness as compared with singletons.Contact: kdm16@psu.eduSupplementary information: Please see additional files.Approximately half of human genes are members of duplicate gene families [1] and such genes might be playing an important role in the robustness of organisms against mutations (reviewed in [2-4]). Do most duplicate genes retain the functions of their parental singleton gene? Or do they diverge after duplication? And how rapidly does this divergence occur? Several models predicting preservation of both duplicate gene copies (e.g., gene function conservation, subfunctionalization, neofunctionalization, and subneofunctionalization) have been proposed [5-7] and