Experimental design and statistical rigor in phylogenomics of horizontal and endosymbiotic gene transfer.

A growing number of phylogenomic investigations from diverse eukaryotes are examining conflicts among gene trees as evidence of horizontal gene transfer. If multiple foreign genes from the same eukaryotic lineage are found in a given genome, it is increasingly interpreted as concerted gene transfers during a cryptic endosymbiosis in the organism's evolutionary past, also known as "endosymbiotic gene transfer" or EGT. A number of provocative hypotheses of lost or serially replaced endosymbionts have been advanced; to date, however, these inferences largely have been post-hoc interpretations of genomic-wide conflicts among gene trees. With data sets as large and complex as eukaryotic genome sequences, it is critical to examine alternative explanations for intra-genome phylogenetic conflicts, particularly how much conflicting signal is expected from directional biases and statistical noise. The availability of genome-level data both permits and necessitates phylogenomics that test explicit, a priori predictions of horizontal gene transfer, using rigorous statistical methods and clearly defined experimental controls.