Cell competition removes segmental aneuploid cells from Drosophila imaginal 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 (<i>Rp</i>) gene mutations are also eliminated, by cell competition with normal cells. Because <i>Rp</i> 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 <i>Rp</i> gene dose, whereas cells with normal doses of the <i>Rp</i> and <i>eIF2γ</i> genes survived and differentiated adult tissues. Thus, cell competition, triggered by differences in <i>Rp</i> gene dose between cells, is a significant mechanism for the elimination of aneuploid somatic cells, likely to contribute to preventing cancer.