Genetic composition of an exponentially growing cell population
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Publication:2229554
Abstract: We study a simple model of DNA evolution in a growing population of cells. Each cell contains a nucleotide sequence which randomly mutates at cell division. Cells divide according to a branching process. Following typical parameter values in bacteria and cancer cell populations, we take the mutation rate to zero and the final number of cells to infinity. We prove that almost every site (entry of the nucleotide sequence) is mutated in only a finite number of cells, and these numbers are independent across sites. However independence breaks down for the rare sites which are mutated in a positive fraction of the population. The model is free from the popular but disputed infinite sites assumption. Violations of the infinite sites assumption are widespread while their impact on mutation frequencies is negligible at the scale of population fractions. Some results are generalised to allow for cell death, selection, and site-specific mutation rates. For illustration we estimate mutation rates in a lung adenocarcinoma.
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Cited in
(10)- Mutation frequencies in a birth-death branching process
- Parameter estimation from single patient, single time-point sequencing data of recurrent tumors
- Modeling DNA methylation in a population of cancer cells
- Population genetics of neutral mutations in exponentially growing cancer cell populations
- A rapid-mutation approximation for cell population dynamics
- Site frequency spectrum of a rescued population under rare resistant mutations
- Forward and backward evolutionary processes and allele frequency spectrum in a cancer cell population
- Accumulation of neutral mutations in growing cell colonies with competition
- Exact site frequency spectra of neutrally evolving tumors: a transition between power laws reveals a signature of cell viability
- Traveling waves of selective sweeps
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