This system was firstly described in 1989 by Fields and Song using "Saccharomyces cerevisiae" as biological model. Yeast two hybrid allows the identification of pairwise PPIs (binary method) "in vivo", in which the two proteins are tested for biophysically direct interaction. The Y2H is based on the functional reconstitution of the yeast transcription factor Gal4 and subsequent activation of a selective reporter such as His3. To test two proteins for interaction, two protein expression constructs are made: one protein (X) is fused to the Gal4 DNA-binding domain (DB) and a second protein (Y) is fused to the Gal4 activation domain (AD). In the assay, yeast cells are transformed with these constructs. Transcription of reporter genes does not occur unless bait (DB-X) and prey (AD-Y) interact with each other and form a functional Gal4 transcription factor. Thus, the interaction between proteins can be inferred by the presence of the products resultant of the reporter gene expression. In cases in which the reporter gene expresses enzymes that allow the yeast to synthesize essential amino acids or nucleotides, yeast growth under selective media conditions indicates that the two proteins tested are interacting.