Synonymous variation was long thought to be neutral (invisible to selection), but in the 50 years since we first began understanding the genetic code, this view has undergone a dramatic shift. A new book on the impact of synonymous mutations (Single Nucleotide Polymorphisms: Human variation and a coming revolution in biology and medicine) includes our chapter outlining the arc of this change in evolutionary thinking about synonymous mutations. Writing this was a lot of fun, and involved a deep dive into papers from the heady days of the discovery of DNA and the genetic code. Other chapters in the book also synthesize an impressive amount of information on the mechanisms driving the effects of synonymous variation, and the role it plays in disease. Hopefully the coming decades will involve increased efforts to understand synonymous variation!
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