My group engineers genetic systems that dramatically accelerate the speed of gene evolution so that we can drive the rapid evolution of new biomolecular functions and prospectively watch (and systematically manipulate) the course of long gene evolutionary processes on laboratory timescales. I will share a recent upgrading of our orthogonal DNA replication system (OrthoRep) to enable the experimental evolution of chosen genes at 1-million times the genomic error rate in vivo. This allowed us to extensively adapt and diverge an enzyme in a way that generates enormous diversity, from which we were able to detect new selective forces shaping how the gene evolved in vivo. I will also share work on the application of OrthoRep to antibody and enzyme engineering.