Open AccessSignatures of neutral evolution in exponentially growing tumors: A theoretical perspective
Author(s) -
Hwai-Ray Tung,
Rick Durrett
Publication year - 2021
Publication title -
plos computational biology/plos computational biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.628
H-Index - 182
eISSN - 1553-7358
pISSN - 1553-734X
DOI - 10.1371/journal.pcbi.1008701
Subject(s) - neutral theory of molecular evolution , exponential growth , perspective (graphical) , spectrum (functional analysis) , statistical physics , type (biology) , contrast (vision) , evolutionary biology , biology , population , frequency spectrum , broad spectrum , physics , statistics , mathematics , computer science , demography , sociology , ecology , artificial intelligence , spectral density , quantum mechanics , chemistry , optics , combinatorial chemistry
Recent work of Sottoriva, Graham, and collaborators have led to the controversial claim that exponentially growing tumors have a site frequency spectrum that follows the 1/ f law consistent with neutral evolution. This conclusion has been criticized based on data quality issues, statistical considerations, and simulation results. Here, we use rigorous mathematical arguments to investigate the site frequency spectrum in the two-type model of clonal evolution. If the fitnesses of the two types are λ 0 < λ 1 , then the site frequency spectrum is c / f α where α = λ 0 /λ 1 . This is due to the advantageous mutations that produce the founders of the type 1 population. Mutations within the growing type 0 and type 1 populations follow the 1/ f law. Our results show that, in contrast to published criticisms, neutral evolution in an exponentially growing tumor can be distinguished from the two-type model using the site frequency spectrum.