Resolving Difficult Phylogenetic Questions: Why More Sequences Are Not Enough

In the quest to reconstruct the Tree of Life, researchers have increasingly turned to phylogenomics, the inference of phylogenetic relationships using genome-scale data (Box 1). Mesmerized by the sustained increase in sequencing throughput, many phylogeneticists entertained the hope that the incongruence frequently observed in studies using single or a few genes 1 would come to an end with the generation of large multigene datasets. Yet, as so often happens, reality has turned out to be far more complex, as three recent large-scale analyses, one published in PLoS Biology 2–4, make clear. The studies, which deal with the early diversification of animals, produced highly incongruent (Box 2) findings despite the use of considerable sequence data (see Figure 1). Clearly, merely adding more sequences is not enough to resolve the inconsistencies. Here, taking these three studies as a case in point, we discuss pitfalls that the simple addition of sequences cannot avoid, and show how the observed incongruence can be largely overcome and how improved bioinformatics methods can help reveal the full potential of phylogenomics.