A New Method to Localize and Test the Significance of Incongruence: Detecting Domain Shuffling in the Nuclear Receptor Superfamily

Abstract

When a data set is partitioned, the resulting subsets may contain phylogenetically conflicting signals if they have different evolutionary histories. In a data set with many taxa, a single taxon that contains multiple phylogenetic histories may result in global incongruence, but no methods are available in a parsimony framework to localize incongruence to specific clades in 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 partitions for any clade in a phylogeny and to test the statistical significance of that conflict by using a metric called the local incongruence length difference. We apply this method to the evolutionary history of the nuclear receptor superfamily, a large group of transcriptional regulators that play essential 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 appropriate ligand. We have performed combined and separate phylogenetic analyses of these two domains and have tested the hypothesis that nuclear receptors evolved by a simple process of lineage splitting and divergence, without domain shuffling or other forms of sequence transfer between proteins. Our analysis indicates that significant conflict exists between the partitined domains at a few nodes on the tree, suggesting that several groups of receptors are "hybrid proteins" formed by domain shuffling or other forms of sequence transfer between more ancient nuclear receptors.

Protein Evolution by Molecular Tinkering: Diversification of the Nuclear Receptor Superfamily from a Ligand-Dependent Ancestor

“…The alignment includes the DBDs and LBDs of the complete NR complements in 11 sequenced genomes from eight broadly sampled animal phyla, plus NRs from 30 other species strategically chosen to maximize phylogenetic accuracy and minimize redundant signal [21]. Unlike previous studies, which used sparser sequence sampling and/or less powerful methods [14],[18],[22], phylogenetic analysis of this alignment using maximum likelihood yielded a well-resolved phylogeny (Figures 1, S2) with strong support for the placement of the basal metazoan sequences and for the relationships among most major NR families. (A few aspects of the topology, however, had weak support, such as whether the SF-1 class has a monophyletic or paraphyletic relationship to the group containing the steroid hormone receptors.)…”