title: DNA copy number evolution in Drosophila cell lines.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.forename: Hangnoh
authors.initials: H
authors.lastname: Lee
authors.forename: C Joel
authors.initials: CJ
authors.lastname: McManus
authors.forename: Dong-Yeon
authors.initials: DY
authors.lastname: Cho
authors.forename: Matthew
authors.initials: M
authors.lastname: Eaton
authors.forename: Fioranna
authors.initials: F
authors.lastname: Renda
authors.forename: Maria Patrizia
authors.initials: MP
authors.lastname: Somma
authors.forename: Lucy
authors.initials: L
authors.lastname: Cherbas
authors.forename: Gemma
authors.initials: G
authors.lastname: May
authors.forename: Sara
authors.initials: S
authors.lastname: Powell
authors.forename: Dayu
authors.initials: D
authors.lastname: Zhang
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhan
authors.forename: Alissa
authors.initials: A
authors.lastname: Resch
authors.forename: Justen
authors.initials: J
authors.lastname: Andrews
authors.forename: Susan E
authors.initials: SE
authors.lastname: Celniker
authors.forename: Peter
authors.initials: P
authors.lastname: Cherbas
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Przytycka
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gatti
authors.forename: Brian
authors.initials: B
authors.lastname: Oliver
authors.forename: Brenton
authors.initials: B
authors.lastname: Graveley
authors.forename: David
authors.initials: D
authors.lastname: MacAlpine
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004247:DNA / Q000032:analysis; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D018628:Gene Dosage; D056084:Genetic Fitness; D014644:Genetic Variation; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D012730:Sex Chromosomes / Q000235:genetics; D046509:Tissue Culture Techniques
chemical_list: D029721:Drosophila Proteins; D035683:MicroRNAs; C471146:bantam microRNA, Drosophila; D004247:DNA; C438368:Pvr protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases