Newly developed structure-based methods do not outperform standard sequence-based methods for large-scale phylogenomics

Abstract

AbstractRecent developments in protein structure prediction have allowed the use of this previously limited source of information at genome-wide scales. It has been proposed that the use of structural information may offer advantages over sequences in phylogenetic reconstruction, due to their slower rate of evolution and direct correlation to function. Here, we examined how recently developed methods for structure-based homology search and tree reconstruction compare to current state-of-the-art sequence-based methods in reconstructing genome-wide collections of gene phylogenies (i.e. phylomes). Our findings reveal that sequence-based methods outperform current structure-based methods both in homology search and accuracy of phylogenetic reconstruction. While structure-based methods can be useful in specific scenarios, their current performance does not justify transitioning from sequence to structured-based methods in large-scale phylogenetic studies. These insights help guide the use of structural data in comparative genomics and highlight the need to continue improving structure-based approaches.