Genetic composition of an exponentially growing cell population

David Cheek, Tibor Antal

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 cellsto 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.
Original languageEnglish
Pages (from-to)6580-6624
Number of pages68
JournalStochastic processes and their applications
Volume130
Issue number11
Early online date5 Jun 2020
DOIs
Publication statusE-pub ahead of print - 5 Jun 2020

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