Table 1.

Comparison of selection strategies for polymerase evolution

Strategy	Advantages	Disadvantages
Phage Display	•Straightforward to select for modifications in primer, template and/or nucleotide triphsophate, including modifications in both strands simultaneously; •Control of selection pressure; •Challenging conditions easy to apply; •Selection possible without amplification and even with the incorporation of a single nucleotide.	•Cross reactivity with sufficient enrichment, mandating the use of post-selection screen; •Complicated.
CSR and derivatives	•No cross reaction between mutants; •Challenging conditions easy to apply.	•Requires amplification to select for modifications in both strands of DNA; •Less control over selection pressure. •Complicated.
Genetic complementation and derivatives	•No cross reaction between mutants; •Sufficient activity to replicate genome ensured •Simple.	• Only natural substrates possible; •Selection pressure difficult to control.
Autogene selection and derivatives	•No cross reaction between mutants •Simple.	•Only natural substrates possible; •Selection pressure difficult to control.