Asymmetric clustering of centrosomes defines the early evolution of tetraploid cells

Abstract

Tetraploidy has long been of interest to both cell and cancer biologists, partly because of its documented role in tumorigenesis. A common model proposes that the extra centrosomes that are typically acquired during tetraploidization are responsible for driving tumorigenesis. However, tetraploid cells evolved in culture have been shown to lack extra centrosomes. This observation raises questions about how tetraploid cells evolve and more specifically about the mechanisms(s) underlying centrosome loss. Here, using a combination of fixed cell analysis, live cell imaging, and mathematical modeling, we show that populations of newly formed tetraploid cells rapidly evolve in vitro to retain a near-tetraploid chromosome number while losing the extra centrosomes gained at the time of tetraploidization. This appears to happen through a process of natural selection in which tetraploid cells that inherit a single centrosome during a bipolar division with asymmetric centrosome clustering are favored for long-term survival.