dosage sensitivity shapes the evolution of copy-number varied regions剂量敏感性形状的进化人类基因组不同区域.pdfVIP

Dosage Sensitivity Shapes the Evolution of Copy-Number Varied Regions ¨ 1 2 2 Benjamin Schuster-Bockler , Donald Conrad , Alex Bateman * 1 European Molecular Biology Laboratory-Centre for Genomic Regulation Systems Biology Unit, Centre for Genomic Regulation, Barcelona, Spain, 2 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom Abstract Dosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV) allow an analysis of the most recent and ongoing evolution. Provided that heterozygous gene deletions and duplications actually change gene dosage, we expect to observe negative selection against CNVs encompassing dosage sensitive genes. In this study, we make use of several sources of population genetic data to identify selection on structural variations of dosage sensitive genes. We show that CNVs can directly affect expression levels of contained genes. We find that genes encoding members of protein complexes exhibit limited expression variation and overlap significantly with a manually derived set of dosage sensitive genes. We show that complexes and other dosage sensitive genes are underrepresented in CNV regions, with a particular bias against frequent variations and duplications. These results suggest that dosage sensitivity is a significant force of negative selection on regions of copy-number variation. ¨ Citation: Schuster-Bockler B, Conrad D, Bateman A (2010) Dosage Sensitivity Shapes the Evolution of Copy-Number Varied Regions. PLoS ONE 5(3): e9474. doi:10.1371/journal.pone.00094