Array Comparative Genomic Hybridizations: Assessing the ability to recapture evolutionary relationships using an in silico approach

BACKGROUND: Comparative Genomic Hybridization (CGH) with DNA microarrays has many biological applications including surveys of copy number changes in tumorogenesis, species detection and identification, and functional genomics studies among related organisms. Array CGH has also been used to infer phylogenetic relatedness among species or strains. Although the use of the entire genome can be seen as a considerable advantage for use in phylogenetic analysis, few such studies have questioned the reliability of array CGH to correctly determine evolutionary relationships. A potential flaw in this application lies in the fact that all comparisons are made to a single reference species. This situation differs from traditional DNA sequence, distance-based phylogenetic analyses where all possible pairwise comparisons are made for the isolates in question. By simulating array data based on the Neurospora crassa genome, we address this potential flaw and other questions regarding array CGH phylogeny. RESULTS: Our simulation data indicates that having a single reference can, in some cases, be a serious limitation when using this technique. Additionally, the tree building process with a single reference is sensitive to many factors including tree topology, choice of tree reconstruction method, and the distance metric used. CONCLUSIONS: Without prior knowledge of the topology and placement of the reference taxon in the topology, the outcome is likely to be wrong and the error undetected. Given these limitations, using CGH to reveal phylogeny based on sequence divergence does not offer a robust alternative to traditional phylogenetic analysis.