Drosophila melanogaster is a proven model system for many aspects of human biology. Here we present a two-hybrid-based protein-interaction map of the fly proteome. A total of 10,623 predicted transcripts were isolated and screened against standard and normalized complementary DNA libraries to produce a draft map of 7048 proteins and 20,405 interactions. A computational method of rating two-hybrid interaction confidence was developed to refine this draft map to a higher confidence map of 4679 proteins and 4780 interactions. Statistical modeling of the network showed two levels of organization: a short-range organization, presumably corresponding to multiprotein complexes, and a more global organization, presumably corresponding to intercomplex connections. The network recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components. This map serves as a starting point for a systems biology modeling of multicellular organisms, including humans.

SignificanceIt is a tenet of modern biology that species adapt through natural selection to cope with the ever-changing environment. By comparing genetic variants between the island and mainland populations of a passerine, we inferred the related age of genetic variants across its entire genome and suggest that preexisting standing variants played the predominant role in local adaptation. Our findings not only resolve a long-standing fundamental problem in biology regarding the genetic sources of adaptation, but imply that the evolutionary potential of a population is highly associated with its preexisting genetic variation.

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