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

ABSTRACT 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 ( Rp ) gene mutations are also eliminated, by cell competition with normal cells. Because Rp genes are spread across the genome, their copy number is a marker for chromosome aberrations. Elimination of imaginal disc cells with irradiation-induced genome damage often required cell competition genes. When defined chromosome regions were deleted, segmentally-aneuploid cells were eliminated by the RpS12-Xrp1 cell competition pathway in an apoptosis- dependent manner when they differed from neighboring cells in Rp gene dose. Cells with normal doses of the Rp (and eIF2γ ) genes survived and differentiated adult tissues. Thus, cell competition, triggered by differences in Rp gene dose between cells, is a significant mechanism for the elimination of aneuploid somatic cells, likely to contribute to preventing cancer.