RT Journal Article
SR Electronic
T1 Patterns of selection against centrosome amplification in human cell lines
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.24.918615
DO 10.1101/2020.01.24.918615
A1 Marco António Dias Louro
A1 Mónica Bettencourt-Dias
A1 Claudia Bank
YR 2020
UL http://biorxiv.org/content/early/2020/01/25/2020.01.24.918615.abstract
AB The presence of extra centrioles, or centrosome amplification, is a hallmark of cancer cells. Centriole numbers in cancer cell populations appear to be at an equilibrium maintained by centriole overproduction and selection, reminiscent of mutation-selection balance. It is not known if the interaction between centriole overproduction and selection can quantitatively explain the intra- and inter-population heterogeneity in centriole numbers.Here, we define mutation-selection-like models and employ a model selection approach to infer patterns of centriole overproduction and selection in a diverse panel of cell lines. Surprisingly, we infer strong and uniform selection against any number of extra centrioles, in most cell lines. However, we do not detect significant differences in parameter estimates between different cell lines. Finally we assess the accuracy and precision of our inference method and find that it increases non-linearly as a function of the number of sampled cells. We discuss the biological implications of our results and how our methodology can inform future experiments.