Abstract
Gene duplication provides much of the raw material from which functional diversity evolves. Two evolutionary mechanisms have been proposed that generate functional diversity: neofunctionalization, the de novo acquisition of function by one duplicate, and subfunctionalization, the partitioning of ancestral functions between gene duplicates. With protein interactions as a surrogate for protein functions, evidence of prodigious neofunctionalization and subfunctionalization has been identified in analyses of empirical protein interactions and evolutionary models of protein interactions. However, we have identified three phenomena that have contributed to neofunctionalization being erroneously identified as a significant factor in protein interaction network evolution. First, self-interacting proteins are underreported in interaction data due to biological artifacts and design limitations in the two most common high-throughput protein interaction assays. Second, evolutionary inferences have been drawn from paralog analysis without consideration for concurrent and subsequent duplication events. Third, the theoretical model of prodigious neofunctionalization is unable to reproduce empirical network clustering and relies on untenable parameter requirements. In light of these findings, we believe that protein interaction evolution is more persuasively characterized by subfunctionalization and self-interactions.
Highlights
Gene duplication is readily accepted as a primary mechanism for generating organismal complexity
We describe in detail the effect underreported data in proteomic assays, misinterpreted interaction data, and model topology have had on the analyses and models which promote ubiquitous neofunctionalization
Gene duplication is generally accepted as a key component of evolution, and protein interactions provide an attractive construct for studying the role of neofunctionalization, subfunctionalization, and homomeric duplication in evolution
Summary
Gene duplication is readily accepted as a primary mechanism for generating organismal complexity. While under neutral selection one of the duplicates can accumulate random mutations and potentially acquire novel and beneficial functions [1]. Subfunctionalization states that both gene duplicates acquire mutations resulting in each duplicate assuming a complementary subset of the ancestral gene’s original functions [2]. Gene duplication and subsequent neofunctionalization and subfunctionalization have straightforward analogs in models of protein interaction network (PIN) evolution. Gene duplication is modeled by copying a protein node in the network along with its interactions. Neofunctionalization and subfunctionalization are modeled by the gain and loss of interactions respectively This straightforward representation has made PINs an attractive target for the study of evolution
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