The interplay between genome and network evolution in eukaryotes

BACKGROUND: Although functionally related proteins can be reliably predicted from phylogenetic profiles, many functional modules do not seem to evolve cohesively according to case studies and systematic analyses in prokaryotes. METHODOLOGY: In this study we quantify the extent of evolutionary cohesiveness of functional modules in eukaryotes and probe the biological and methodological factors influencing our estimates. We have collected various datasets of protein complexes and pathways in S. cerevisiae. We define orthologous groups on 34 eukaryotic genomes and measure the extent of cohesive evolution of sets of orthoogous groups of which members constitute a known complex or pathway. Within this framework it appears that most functional modules evolve flexibly, rather than cohesively. CONCLUSIONS: Even after correcting for uncertain module definitions and potentially problematic orthologous groups, only 46% of pathways and complexes evolves more cohesively than random modules. This flexibility seems partly coupled to the nature of the functional module as biochemical pathways are generally more cohesively evolving than complexes. Author’s summary Components of a protein complex or a metabolic pathway strongly cooperate to perform a specific function. Because of this functional interdependence, proteins that form a complex or pathway are expected to be present and absent together in different species. Phylogenetic profiling methods, in which proteins with similar presence and absence patterns are inferred to be functionally linked, are based on this assumption. In this report, we quantify to what extent proteins that together constitute a complex or pathway (a functional module) in yeast are present and absent together (evolve cohesively) in other eukaryotic species. We find that more than half of all complexes and pathways are only partially present in a number of species. It appears that evolution of functional modules is very flexible; components are not indispensable; they can be replaced or reused in a different functional context. This places a limit on how well phylogenetic profiling methods can detect functionally related proteins. Functional modules that evolve cohesively are typically involved in biological processes such as translation and amino acid metabolism.