Genotype-phenotype linkage for directed evolution and screening of combinatorial protein libraries

The technologies for screening peptide and protein libraries for studies in the fields of directed protein evolution and functional genomics have advanced with astonishing speed. For screening of functional proteins, three technologies are required: (i) the construction of a gene library (genotype), (ii) the establishment of a linkage between each protein (phenotype) and its encoding gene (genotype), and (iii) the selection of desired proteins (phenotype) from the library. This review highlights the genotype-phenotype linkage technologies, which can be classified into three types; that is, cell-type linkage, virus-type linkage, and array-type linkage methods. These methods are summarized, and their advantages and disadvantages are discussed.