Project description:Thomas Hunt Morgan and colleagues identified variation in gene copy number in Drosophila in the 1920s and 1930s and linked such variation to phenotypic differences [Bridges, C. B. (1936) Science 83, 210]. Yet the extent of variation in the number of chromosomes, chromosomal regions, or gene copies, and the importance of this variation within species, remain poorly understood. Here, we focus on copy-number variation in Drosophila melanogaster. We characterize copy-number polymorphism (CNP) across genomic regions, and we contrast patterns to infer the evolutionary processes acting on this variation. Copy-number variation in D. melanogaster is non-randomly distributed, presumably due to a mutational bias produced by tandem repeats or other mechanisms. Comparisons of coding and noncoding CNPs, however, reveal a strong effect of purifying selection in the removal of structural variation from functionally constrained regions. Most patterns of CNP in D. melanogaster suggest that negative selection and mutational biases are the primary agents responsible for shaping structural variation. Keywords: comparative genomic hybridization
Project description:The extent to which differences in germ line DNA copy number contribute to natural phenotypic variation is unknown. We analyzed the copy number content of the mouse genome to a sub-10 kb resolution. We identified over 1,300 copy number variant regions (CNVRs), most of which are < 10 kb in length, are found in more than one strain, and, in total, span 3.2% (85 Mb) of the genome. To assess the potential functional impact of copy number variation, we mapped expression profiles of purified hematopoietic stem and progenitor cells, adipose tissue and hypothalamus to CNVRs in cis. Of the more than 600 significant associations between CNVRs and expression profiles, most map to CNVRs outside of the transcribed regions of genes. In hematopoietic stem/progenitor cells, up to 28% of strain-dependent expression variation is associated with copy number variation, supporting the role of germ line CNVs as major contributors to natural phenotypic variation in the laboratory mouse.
