Template selection during manipulation of complex mixtures by PCR

PCR is ubiquitous in molecular biology. It is used to amplify single sequen ces from large genomes, or populations of sequences from complex mixtures s uch as cDNA libraries in mammalian cells. These cDNA libraries are often em ployed in subsequent labor-intensive experiments such as genetic screens, t he outcome of which depends on library quality. The use of PCR to amplify d iverse sequence populations raises important technical issues. One question is whether or not PCR is capable of maintaining population diversity, spec ifically with respect to template selection in the first rounds of the ampl ification process (i.e. the possibility that rare sequences in a complex mi xture are lost because of amplification failure at the onset of the PCR). H ere, we analyze the properties of PCR in the context of template selection in complex mixtures and show that it is an excellent method for preserving diversity.