DNA copy number evolution in Drosophila cell lines

• Published in: Genome biology Vol. 15; no. 8; p. R70
• Main Authors: Lee, Hangnoh, McManus, C Joel, Cho, Dong-Yeon, Eaton, Matthew, Renda, Fioranna, Somma, Maria Patrizia, Cherbas, Lucy, May, Gemma, Powell, Sara, Zhang, Dayu, Zhan, Lijun, Resch, Alissa, Andrews, Justen, Celniker, Susan E, Cherbas, Peter, Przytycka, Teresa M, Gatti, Maurizio, Oliver, Brian, Graveley, Brenton, MacAlpine, David
• Format: Journal Article
• Language: English
• Published: London BioMed Central 28.08.2014
• Subjects: Animal Genetics and Genomics; Animals; Bantam; BASIC BIOLOGICAL SCIENCES; biochemical pathways; Bioinformatics; Biomedical and Life Sciences; carcinogenesis; Cell Line; Cell Survival; copy number change; data coordination center; DNA; DNA - analysis; dosage compensation; Drosophila; Drosophila melanogaster - cytology; Drosophila melanogaster - genetics; Drosophila Proteins - genetics; Evolution, Molecular; Evolutionary Biology; Female; fourth chromosome; Gene Dosage; Genetic Fitness; Genetic Variation; Human Genetics; Kc167 cell; Life Sciences; Male; Microbial Genetics and Genomics; microRNA; MicroRNAs - genetics; natural selection; neoplasm cells; neoplasms; phenotype; Plant Genetics and Genomics; proto-oncogenes; Receptor Protein-Tyrosine Kinases - genetics; Selection, Genetic; sequence analysis; Sequence Analysis, DNA; Sex Chromosomes - genetics; tissue culture; Tissue Culture Techniques; tumor suppressor genes; vascular endothelial growth factor receptors; vascular endothelial growth factors; Fourth Chromosome; Kc167 Cell; Copy Number Change; Data Coordination Center; Dosage Compensation
• ISSN: 1474-760X; 1465-6906; 1474-760X; 1465-6914
• DOI: 10.1186/gb-2014-15-8-r70

Background Structural rearrangements of the genome resulting in genic imbalance due to copy number change are often deleterious at the organismal level, but are common in immortalized cell lines and tumors, where they may be an advantage to cells. In order to explore the biological consequences of copy number changes in the Drosophila genome, we resequenced the genomes of 19 tissue-culture cell lines and generated RNA-Seq profiles. Results Our work revealed dramatic duplications and deletions in all cell lines. We found three lines of evidence indicating that copy number changes were due to selection during tissue culture. First, we found that copy numbers correlated to maintain stoichiometric balance in protein complexes and biochemical pathways, consistent with the gene balance hypothesis. Second, while most copy number changes were cell line-specific, we identified some copy number changes shared by many of the independent cell lines. These included dramatic recurrence of increased copy number of the PDGF/VEGF receptor, which is also over-expressed in many cancer cells, and of bantam , an anti-apoptosis miRNA. Third, even when copy number changes seemed distinct between lines, there was strong evidence that they supported a common phenotypic outcome. For example, we found that proto-oncogenes were over-represented in one cell line ( S2-DRSC ), whereas tumor suppressor genes were under-represented in another ( Kc167 ). Conclusion Our study illustrates how genome structure changes may contribute to selection of cell lines in vitro . This has implications for other cell-level natural selection progressions, including tumorigenesis.