Drosophila Cell Lines to Model Selection for Aneuploid States

Abstract

Abnormal numbers of chromosomes, or aneuploid segments of chromosomes, are associated with multiple\rgenetic disorders and cancers. In many chromosomal abnormalities, it is thought that genic balance of protein\rcomplexes or pathways are disrupted. In cancers and immortal cell lines, it is thought that aneuploidy confers a\rgrowth and senescence advantage. The karyotype and gene expression profiles of 19 Drosophila modENCODE\rcell lines highlight the evolution of advantageous gene copy numbers while maintaining genic balance. These\rhighly aneuploid cells show coherent changes in copy number among genes encoding components of multiprotein\rcomplexes, which may reflect strong selection for genic balance. They also show copy number increases in genes\rthat positively regulate cell cycle progression or decreases in copy number of genes that negatively regulate cell\rcycle progression, highlighting multiple evolutionary paths to increased growth. Some copy number changes, both\rincreases and decreases, are recurrent. This suggests that there are some critical primary drivers of evolving the\rability to grow in vitro. The small, highly rearranged genome, of Drosophila cell lines provides a powerful model\rsystem for studying numerical changes in genome, their effect, and dosage compensation against the effect.