Really excited to share the first chapter of my PhD on how genome-wide linkage in cancer reduces the efficacy of selection via Hill-Robertson interference (HRI), with mentors @cd_mcfarland, @PetrovADmitri and @cncurtis. https://bit.ly/2lTDQnT (1/10)
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Finally, we demonstrate that a simple evolutionary model incorporating HRI can explain these observed patterns of selection and allowed us to estimate the mean fitness effects of passengers (~1%) and drivers (~18%) – much larger than previously estimated. (8/10)
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Thus, this allowed us to estimate that in elevated mutational burden tumors (>95% of cancers), deleterious passengers accumulate and confer an individually-weak, but collectively-substantial fitness cost of ~40% that impacts tumor progression. (9/10)
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How successful tumors overcome this deleterious load is an exciting, open question. Similar to constraints in germ-line evolution, we think that preventing protein mis-folding is an important first step. We’d love to hear what you think! (10/10)
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