Detecting the limits of regulatory element conservation and divergence estimation using pairwise and multiple alignments

Background: Molecular evolutionary studies of noncoding sequences rely on multiple alignments. Yet how multiple alignment accuracy varies across sequence types, tree topologies, divergences and tools, and further how this variation impacts specific inferences, remains unclear. Results: Here we develop a molecular evolution simulation platform, CisEvolver, with models of background noncoding and transcription factor binding site evolution, and use simulated alignments to systematically examine multiple alignment accuracy and its impact on two key molecular evolutionary inferences: transcription factor binding site conservation and divergence estimation. We find that the accuracy of multiple alignments is determined almost exclusively by the pairwise divergence distance of the two most diverged species and that additional species have a negligible influence on alignment accuracy. Conserved transcription factor binding sites align better than surrounding noncoding DNA yet are often found...

• Type: Journal
• Year: 2006
• Where: BMCBI
• Authors: Daniel A. Pollard, Alan M. Moses, Venky N. Iyer, Michael B. Eisen
• Keywords: Alignment Accuracy, BMCBI 2006, Multiple Alignment Accuracy, Multiple Alignments