Drosophila Cell Lines to Model Selection for Aneuploid States

Abstract

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