Journal Article

Copy-Number Variation: The Balance between Gene Dosage and Expression in <i>Drosophila melanogaster</i>

Jun Zhou, Bernardo Lemos, Erik B. Dopman and Daniel L. Hartl

in Genome Biology and Evolution

Published on behalf of Society for Molecular Biology and Evolution

Volume 3, issue , pages 1014-1024
Published in print January 2011 |
Published online October 2011 | e-ISSN: 1759-6653 | DOI: http://dx.doi.org/10.1093/gbe/evr023

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Copy-number variants (CNVs) reshape gene structure, modulate gene expression, and contribute to significant phenotypic variation. Previous studies have revealed CNV patterns in natural populations of Drosophila melanogaster and suggested that selection and mutational bias shape genomic patterns of CNV. Although previous CNV studies focused on heterogeneous strains, here, we established a number of second-chromosome substitution lines to uncover CNV characteristics when homozygous. The percentage of genes harboring CNVs is higher than found in previous studies. More CNVs are detected in homozygous than heterozygous substitution strains, suggesting the comparative genomic hybridization arrays underestimate CNV owing to heterozygous masking. We incorporated previous gene expression data collected from some of the same substitution lines to investigate relationships between CNV gene dosage and expression. Most genes present in CNVs show no evidence of increased or diminished transcription, and the fraction of such dosage-insensitive CNVs is greater in heterozygotes. More than 70% of the dosage-sensitive CNVs are recessive with undetectable effects on transcription in heterozygotes. A deficiency of singletons in recessive dosage-sensitive CNVs supports the hypothesis that most CNVs are subject to negative selection. On the other hand, relaxed purifying selection might account for the higher number of protein–protein interactions in dosage-insensitive CNVs than in dosage-sensitive CNVs. Dosage-sensitive CNVs that are upregulated and downregulated coincide with copy-number increases and decreases. Our results help clarify the relation between CNV dosage and gene expression in the D. melanogaster genome.

Keywords: copy-number variation; gene expression; gene dosage sensitivity; recessive CNV; selection

Journal Article.  7150 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology ; Evolutionary Biology ; Genetics and Genomics

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