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Natural selection shapes genome wide patterns of copy number polymorphism in D. melanogaster

ABSTRACT: The role natural selection plays in governing the locations and early evolution of copy number mutations remains largely unexplored. Here we employ high-density full-genome tiling arrays to create a fine-scale genomic map of copy number polymorphisms (CNPs) in Drosophila melanogaster. We inferred a total of 2,658 independent CNPs, 56% of which overlap genes. These include CNPs likely to be under positive selection, most notably high frequency duplications encompassing toxin-response genes. The locations and frequencies of CNPs are strongly shaped by purifying selection with deletions under stronger purifying selection than duplications. Among duplications, those overlapping exons or introns and those falling on the X-chromosome seem to be subject to the strongest purifying selection. In order to characterize copy number polymorphisms (CNPs) in Drosophila malanogaster, we applied comparative genome hybridization (CGH) using tiling arrays covering the full euchromatic genome of Drosophila melanogaster. We inferred copy number changes with a Hidden Markov Model (HMM) that returned the posterior probabilities for copy number by comparing DNA hybridization intensities between natural isolates and the reference genome strain. Training data for copy number changes were obtained via hybridization with a line known to contain a ~200kb homozygous duplication and from a set of 52 validated homozygous deletions. The probabilities of mutation were parsed to make CNP calls. Key words: comparative genomic hybridization, CGH, copy number polymorphism, CNP, copy number variation, CNV, duplication, deletion

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE11326 | GEO | 2008/06/06

SECONDARY ACCESSION(S): PRJNA106647

REPOSITORIES: GEO

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Project description:Gene copy-number variation, which provides the raw material for the evolution of novel genes, is surprisingly widespread in natural populations. Experimental evolution studies have demonstrated an extremely high spontaneous rate of origin of gene duplications. When organisms are suboptimally adapted to their environment, gene duplication may compensate for reduced fitness by amplifying promiscuous activity of a gene, or increasing dosage of a suboptimal gene. The overarching goal of this study is to inverstigate whether CNVs constitute a common mechanism of adaptive genetic change during compensatory evolution and to further characterize the role of natural selection in dictating their evolutionary spread at a population-genomic level. Outcrossing populations of C. elegans with low fitness were evolved for >200 generations and the frequencies of CNVs in these populations were analyzed by oligonucleotide array comparative genome hybridization, quantitative PCR, and single-worm PCR. Multiple duplications and deletions were detected in intermediate to high frequencies and several lines of evidence suggest that the changes in frequency were adaptive. 1) Many copy-number changes reached high frequency, were near fixation, or were fixed in a short time. 2) Many independent duplications and deletions in high frequency harbor overlapping regions which likely include genes that are under selection for either higher or lower rates of expression. 3) The size spectrum of deuplications and deletions in the adaptive recovery populations is significantly larger than that of spontaneous copy-number variants in mutation accumulation experiments. This is expected if larger CNVs are more likely to encompass genes that are being selected for altered gene dosage. Out results validate the great potential borne by gene copy-number changes for compensatory evolution and adaptation. Experimental genome evolution of copy-number variants in 25 experimental lines compared to 5 ancestral control lines.

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Natural selection shapes genome wide patterns of copy number polymorphism in D. melanogaster

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