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This Club EvMed event occurred on April 26th, 2023. Learn more about Club EvMed at https://clubevmed.org. This conversation was led by Laurence Hurst, Professor of Evolutionary Genetics and Director of The Milner Centre for Evolution at the University of Bath. Knowing what is evolutionarily functional in the genome is important for diagnostics (which mutations might cause disease) and for new modes of therapy (can I engineer a replacement gene, where should I put a replacement gene). In this talk I’ll look at how understanding the evolution of genes at the synonymous sites (ones at which mutations don’t alter the amino acid encoded) can enable better understanding of which mutations are functional, why they cause disease (despite being “silent”) and enable expression of genes for gene therapy that have otherwise proven hard to express.