From evolution at synonymous sites to improve gene therapy and diagnostics by Laurence Hurst

As part of the Mendel @200 webinar series. Professor Laurence Hurst made this presentation on 18th May 2023. Understanding what is functional (under selection) in our genome is important both for improved genetic diagnostics and for construction of modified genes for gene therapy and biotech. Alteration of synonymous sites is a commonly performed and permitted means of engineering optimal transgenes. Asking whether selection can act on synonymous mutations in humans is thus more than an exercise in understanding the limits of natural selection. In this talk I’ll consider recent progress in understanding the mechanisms and commonality of selection on synonymous mutations and in turn examine downstream applications of the insights so gained. Amongst other things, I’ll illustrate how analysis of the evolution of human retrogenes has inspired better understanding of forces operating on synonymous sites and in turn to enabling expression of transgenes that would otherwise be silent.