CURatio: Genome-wide phylogenomic analysis method using ratios of total branch lengths.

Evolutionary hypotheses provide important underpinnings of biological and medical sciences, and comprehensive, genome-wide understanding of evolutionary relationships among organisms are needed to test and refine such hypotheses. Theory and empirical evidence clearly indicate that phylogenies (trees) of different genes (loci) should not display precisely matching topologies. The main reason for such phylogenetic incongruence is reticulated evolutionary history of most species due to meiotic sexual recombination in eukaryotes, or horizontal transfers of genetic material in prokaryotes. Nevertheless, many genes should display topologically related phylogenies, and should group into one or more (for genetic hybrids) clusters in poly-dimensional "tree space". Unusual evolutionary histories or effects of selection may result in "outlier" genes with phylogenies that fall outside the main distribution(s) of trees in tree space. We present a new phylogenomic method, CURatio, which uses ratios of total branch lengths in gene trees to help identify phylogenetic outliers in a given set of ortholog groups from multiple genomes. An advantage of CURatio over other methods is that genes absent from and/or duplicated in some genomes can be included in the analysis. We conducted a simulation study under the coalescent model, and showed that, given sufficient species depth and topological difference, these ratios are significantly higher for the "outlier" gene phylogenies. Also, we applied CURatio to a set of annotated genomes of the fungal family, Clavicipitaceae, and identified alkaloid biosynthesis genes as outliers, probably due to a history of duplication and loss. The source code is available at https://github.com/QiwenKang/CURatio, and the empirical data set on Clavicipitaceae and simulated data set are available at Mendeley https://data.mendeley.com/datasets/mrxts7wjrr/1.