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Mutation timing in a spatial model of evolution

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 نشر من قبل Jasmine Foo
 تاريخ النشر 2020
  مجال البحث علم الأحياء
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Motivated by models of cancer formation in which cells need to acquire $k$ mutations to become cancerous, we consider a spatial population model in which the population is represented by the $d$-dimensional torus of side length $L$. Initially, no sites have mutations, but sites with $i-1$ mutations acquire an $i$th mutation at rate $mu_i$ per unit area. Mutations spread to neighboring sites at rate $alpha$, so that $t$ time units after a mutation, the region of individuals that have acquired the mutation will be a ball of radius $alpha t$. We calculate, for some ranges of the parameter values, the asymptotic distribution of the time required for some individual to acquire $k$ mutations. Our results, which build on previous work of Durrett, Foo, and Leder, are essentially complete when $k = 2$ and when $mu_i = mu$ for all $i$.



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We consider a spatial model of cancer in which cells are points on the $d$-dimensional torus $mathcal{T}=[0,L]^d$, and each cell with $k-1$ mutations acquires a $k$th mutation at rate $mu_k$. We will assume that the mutation rates $mu_k$ are increasi ng, and we find the asymptotic waiting time for the first cell to acquire $k$ mutations as the torus volume tends to infinity. This paper generalizes results on waiting for $kgeq 3$ mutations by Foo, Leder, and Schweinsberg, who considered the case in which all of the mutation rates $mu_k$ were the same. In addition, we find the limiting distribution of the spatial distances between mutations for certain values of the mutation rates.
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