Evolutionary conservation and over-representation of functionally enriched network patterns in the yeast regulatory network

Background: Localized network patterns are assumed to represent an optimal design principle in different biological networks. A widely used method for identifying functional components in biological networks is looking for network motifs - over-represented network patterns. A number of recent studies have undermined the claim that these over-represented patterns are indicative of optimal design principles and question whether localized network patterns are indeed of functional significance. This paper examines the functional significance of regulatory network patterns via their biological annotation and evolutionary conservation. Results: We enumerate all 3-node network patterns in the regulatory network of the yeast S. cerevisiae and examine the biological GO annotation and evolutionary conservation of their constituent genes. Specific 3-node patterns are found to be functionally enriched in different exogenous cellular conditions and thus may represent significant functional components. These functionally enriched patterns are composed mainly of recently evolved genes suggesting that there is no evolutionary pressure acting to preserve such functionally enriched patterns. No correlation is found between over-representation of network patterns and functional enrichment. Conclusion: The findings of functional enrichment support the view that network patterns constitute an important design principle in regulatory networks. However, the wildly used method of over-representation for detecting motifs is not suitable for identifying functionally enriched patterns.