| Autor: |
Stein A; Centre for Cancer Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, UK and Department of Physics, ETH Zurich, Zürich, Switzerland., Kizhuttil R; Department of Physics, Indian Institute of Science Education and Research, Kolkata, India., Bak M; Department of Mathematics, City, University of London, London, UK., Noble R; Department of Mathematics, City, University of London, London, UK. |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 May 02. Date of Electronic Publication: 2024 May 02. |
| DOI: |
10.1101/2023.11.27.568915 |
| Abstrakt: |
Evolution during range expansions shapes biological systems from microbial communities and tumours up to invasive species. A fundamental question is whether, when a beneficial mutation arises during a range expansion, it will evade clonal interference and sweep through the population to fixation. However, most theoretical investigations of range expansions have been confined to regimes in which selective sweeps are effectively impossible, while studies of selective sweeps have either assumed constant population size or have ignored spatial structure. Here we use mathematical modelling and analysis to investigate selective sweep probabilities in the alternative yet biologically relevant scenario in which mutants can outcompete and displace a slowly spreading wildtype. Assuming constant radial expansion speed, we derive probability distributions for the arrival time and location of the first surviving mutant and hence find surprisingly simple approximate and exact expressions for selective sweep probabilities in one, two and three dimensions, which are independent of mutation rate. Namely, the selective sweep probability is approximately 1 - c w t / c m d , where c w t and c m are the wildtype and mutant radial expansion speeds, and d the spatial dimension. Using agent-based simulations, we show that our analytical results accurately predict selective sweep frequencies in the two-dimensional spatial Moran process. We further compare our results with those obtained for alternative growth laws. Parameterizing our model for human tumours, we find that selective sweeps are predicted to be rare except during very early solid tumour growth, thus providing a general, pan-cancer explanation for findings from recent sequencing studies. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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