4.5 Article

Promoting extinction or minimizing growth? The impact of treatment on trait trajectories in evolving populations

期刊

EVOLUTION
卷 77, 期 6, 页码 1408-1421

出版社

OXFORD UNIV PRESS
DOI: 10.1093/evolut/qpad042

关键词

evolutionary rescue; resistance evolution; dormancy; competitive release; immune evasion

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When cancers or bacterial infections occur, a small group of cells need to escape regulation, evolve and adapt to their environment. The shape of the fitness landscape determines the adaptation trajectory of birth and death rates. Treatment strategies targeting both birth and death rates are most effective but increase evolvability. By mapping physiological adaptation pathways and molecular drug mechanisms to traits and treatments with clear eco-evolutionary consequences, we can better understand the dynamics of cancer and bacterial infections.
When cancers or bacterial infections establish, small populations of cells have to free themselves from homoeostatic regulations that prevent their expansion. Trait evolution allows these populations to evade this regulation, escape stochastic extinction and climb up the fitness landscape. In this study, we analyze this complex process and investigate the fate of a cell population that underlies the basic processes of birth, death, and mutation. We find that the shape of the fitness landscape dictates a circular adaptation trajectory in the trait space spanned by birth and death rates. We show that successful adaptation is less likely for parental populations with higher turnover (higher birth and death rates). Including density- or trait-affecting treatment we find that these treatment types change the adaptation dynamics in agreement with a geometrical analysis of fitness gradients. Treatment strategies that simultaneously target birth and death rates are most effective, but also increase evolvability. By mapping physiological adaptation pathways and molecular drug mechanisms to traits and treatments with clear eco-evolutionary consequences, we can achieve a much better understanding of the adaptation dynamics and the eco-evolutionary mechanisms at play in the dynamics of cancer and bacterial infections.

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