Cell competition removes segmental aneuploid cells from imaginal disc-derived tissues based on ribosomal protein gene dose.

Aneuploidy causes birth defects and miscarriages, occurs in nearly all cancers and is a hallmark of aging. Individual aneuploid cells can be eliminated from developing tissues by unknown mechanisms. Cells with ribosomal protein () gene mutations are also eliminated, by cell competition with normal cells. Because genes are spread across the genome, their copy number is a potential marker for aneuploidy. We found that elimination of imaginal disc cells with irradiation-induced genome damage often required cell competition genes. Segmentally aneuploid cells derived from targeted chromosome excisions were eliminated by the RpS12-Xrp1 cell competition pathway if they differed from neighboring cells in gene dose, whereas cells with normal doses of the and genes survived and differentiated adult tissues. Thus, cell competition, triggered by differences in gene dose between cells, is a significant mechanism for the elimination of aneuploid somatic cells, likely to contribute to preventing cancer.