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 (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 eIF2{gamma}) 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.