This article is part of an anniversary issue of Journal of Molecular Evolution, commenting on a paper published on 1999 by the Nobel laureate Frances Arnold and her colleague Kentaro Miyazaki. The paper by Miyazaki and Arnold presented saturation mutagenesis as an alternative method to random mutagenesis for obtaining enzymes with increasing stability. Both techniques were conceived to accomplish directed evolution, an approach honoured by the Nobel Prize of Chemistry 2018. Here, I am commenting on the pros and cons of random and saturation mutagenesis, while also discussing important results from directed evolution. I conclude that molecular evolution is finding new applications in science and it is definitely an integral part of the genomic era's revolution.
Keywords: Enzymes; Fitness; Medicine; Mutation; Natural selection; Neutral evolution; Protein engineering.