A new method to localize and test the significance of incongruence: Detecting domain shuffling in the nuclear receptor superfamily

When a data set is partitioned, the resulting subsets may contain phylogene tically conflicting signals if they have different evolutionary histories. In a data set with many taxa, a single taxon that contains multiple phyloge netic histories may result in global incongruence, but no methods are avail able in a parsimony framework to localize incongruence to specific clades i n a phylogeny or to test the significance of incongruence on a local scale. Here we present a new method to quantify the conflict between data partiti ons for any clads in a phylogeny and to test the statistical significance o f that conflict by using a metric called the local incongruence length diff erence. We apply this method to the evolutionary history of the nuclear rec eptor superfamily, a large group of transcriptional regulators that play es sential roles in metazoan development and physiology. All nuclear receptors are composed of several discrete domains, including one that binds to DNA response elements on specific target genes and another that binds to the ap propriate ligand. We have performed combined and separate phylogenetic anal yses of these two domains and have tested the hypothesis that nuclear recep tors evolved by a simple process of lineage splitting and divergence, witho ut domain shuffling or other forms of sequence transfer between proteins. O ur analysis indicates that significant conflict exists between the partitio ned domains at a few nodes on the tree, suggesting that several groups of r eceptors are "hybrid proteins" formed by domain shuffling or other forms of sequence transfer between more ancient nuclear receptors.