title: Inferring phylogenies of evolving sequences without multiple sequence alignment.
abstract: Alignment-free methods, in which shared properties of sub-sequences (e.g. identity or match length) are extracted and used to compute a distance matrix, have recently been explored for phylogenetic inference. However, the scalability and robustness of these methods to key evolutionary processes remain to be investigated. Here, using simulated sequence sets of various sizes in both nucleotides and amino acids, we systematically assess the accuracy of phylogenetic inference using an alignment-free approach, based on D2 statistics, under different evolutionary scenarios. We find that compared to a multiple sequence alignment approach, D2 methods are more robust against among-site rate heterogeneity, compositional biases, genetic rearrangements and insertions/deletions, but are more sensitive to recent sequence divergence and sequence truncation. Across diverse empirical datasets, the alignment-free methods perform well for sequences sharing low divergence, at greater computation speed. Our findings provide strong evidence for the scalability and the potential use of alignment-free methods in large-scale phylogenomics.
authors.affiliation: Institute for Molecular Bioscience, and ARC Centre of Excellence in Bioinformatics, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Cheong Xin
authors.initials: CX
authors.lastname: Chan
authors.affiliation: Institute for Molecular Bioscience, and ARC Centre of Excellence in Bioinformatics, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bernard
authors.affiliation: 1] Institute for Molecular Bioscience, and ARC Centre of Excellence in Bioinformatics, The University of Queensland, Brisbane, QLD 4072, Australia [2].
authors.forename: Olivier
authors.initials: O
authors.lastname: Poirion
authors.affiliation: School of Electrical Engineering and Computer Science, Queensland University of Technology, Brisbane, QLD 4000, Australia.
authors.forename: James M
authors.initials: JM
authors.lastname: Hogan
authors.affiliation: Institute for Molecular Bioscience, and ARC Centre of Excellence in Bioinformatics, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ragan
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics*; D019295:Computational Biology; D019143:Evolution, Molecular; D010802:Phylogeny; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D012984:Software