[The Svedberg seminar] – The evolution of codon usage bias in humans: the unwanted transcript hypothesis
June 9, 2025 @ 15:15 – 16:15 CEST
Laurence Hurst
Professor of Evolutionary Genetics at The Milner Centre For Evolution
University of Bath UK
Biography
Laurence Hurst is Professor of Evolutionary Genetics at The Milner Centre For Evolution, University of Bath UK, of which he was the founding Director. He works on fundamental problems in the evolution of genetic systems often with application to medicine. He was elected a Fellow of the Academy of Medical Sciences and a Fellow of the Royal Society (FRS) in 2015. He was a recipient of the Humboldt Prize (2024), the VC Research Medal (2015), the Scientific Medal of the Zoological Society of London (2003), the Darwin Award of the BA (2000) and was elected a member of European Molecular Biology Organization (EMBO) in 2004. He was awarded The Genetics Society Medal in 2010 and was its President from 2018-2021. Aside from being on the editorial board of multiple journals, he is on the Scientific Advisory Board of ExpressionEdits and the Advisory Board of PlosB.
The evolution of codon usage bias in humans: the unwanted transcript hypothesis
Although translational selection to favour codons matching the most abundant tRNAs is not readily observed in humans, nonetheless ~20% of synonymous mutations are under selection. We hypothesize that much of this reflects protection against unwanted RNAs – spurious transcripts, mis-spliced forms or RNAs derived from transposable elements or viruses. We propose that selection on synonymous sites functions to reduce the rate of creation of unwanted transcripts and to filter if created. Specifically, high-GC content is both particular to functional native mRNAs and used to recognize transcripts as native. In support of this hypothesis, transcription, nuclear export, liquid phase condensation and RNA degradation promote GC-rich transcripts and suppress AU ones. With such ‘traps’, the codon usage of native genes has, in turn, evolved to avoid such suppression. That parallel filters also affect the endosomal import of RNAs provides common design rules for both transgenes and RNA vaccines.
Host: Matthew Christmas matthew.christmas@imbim.uu.se
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