Abstract
BackgroundStructural 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.ResultsOur 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).ConclusionOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/gb-2014-15-8-r70) contains supplementary material, which is available to authorized users.
Highlights
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
To determine copy number genome-wide, we performed generation DNA sequencing (DNA-Seq) on naked DNA harvested from 19 modENCODE cell lines [32,33,34,35,36,37,38,39,40,41] and control DNA from adult females (Table 1)
Except for regions where unambiguous mapping of reads is complicated by low sequence complexity, we were not able to find any significant overlap between regions of copy number polymorphism in Drosophila animal populations and the copy number regions we identified in the cell lines
Summary
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. Copy number While genes do generally come in pairs, there are a number of situations where gene copy number deviates from fully diploid [1]. Some of these deviations are normal, such as occurs in the case of sex chromosomes [2] and amplification in terminally differentiated cells [3,4]. Copy number changes are abnormal and deleterious, and vary in extent from full chromosomes, to chromosome segments, to focal regions altering the copy number of single genes. Submicroscopic copy number changes of limited extent along a chromosome are often referred to as copy number variants. Recent advancement of genome-wide techniques has made the detection of copy number much easier, and the extent of copy number variants in populations is extensive [7,8]
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