Swap/counter selection: a rapid cloning method

A method for transferring a first library of unique polynucleic acid sequences included in a library of donor vectors into a second library including each of said unique polynucleic acid sequences in the form of an acceptor vector, wherein said donor vectors include a first antibiotic resistance functioning sequence and said acceptor vectors include a second antibiotic resistance functioning sequence, comprising:

• (a) digesting each of said donor vectors of said first library and said acceptor vectors with restriction endonucleases, which digesting releases each of said polynucleic acids from said donor vectors and restricts said acceptor vector such that each of said released polynucleic acids and said restricted donor vector are capable of ligation,
• (b) combining into distinct ligation reaction mixture compartments of a third library, each of the unpurified digestion product including each of said released polynucleic acids of said library and said restricted acceptor vector,
• (c) transferring each of said distinct ligation reaction mixtures into each of a multiplicity of distinct transformation compartments containing host cells and growth medium containing said second antibiotic and transforming said host cells,
• (d) growing distinct colonies of said host cells in each of said compartments in the presence of a compound that changes color in the presence of the expression product of said first antibiotic resistance functioning sequence, and
• (e) collecting host cells including said polynucleic acids contained in said acceptor vectors from colonies that grow in said compartments and that do not exhibit a color change indicating the presence of said first antibiotic resistance functioning sequence.