title: Joint Bayesian estimation of alignment and phylogeny.
abstract: We describe a novel model and algorithm for simultaneously estimating multiple molecular sequence alignments and the phylogenetic trees that relate the sequences. Unlike current techniques that base phylogeny estimates on a single estimate of the alignment, we take alignment uncertainty into account by considering all possible alignments. Furthermore, because the alignment and phylogeny are constructed simultaneously, a guide tree is not needed. This sidesteps the problem in which alignments created by progressive alignment are biased toward the guide tree used to generate them. Joint estimation also allows us to model rate variation between sites when estimating the alignment and to use the evidence in shared insertion/deletions (indels) to group sister taxa in the phylogeny. Our indel model makes use of affine gap penalties and considers indels of multiple letters. We make the simplifying assumption that the indel process is identical on all branches. As a result, the probability of a gap is independent of branch length. We use a Markov chain Monte Carlo (MCMC) method to sample from the posterior of the joint model, estimating the most probable alignment and tree and their support simultaneously. We describe a new MCMC transition kernel that improves our algorithm's mixing efficiency, allowing the MCMC chains to converge even when started from arbitrary alignments. Our software implementation can estimate alignment uncertainty and we describe a method for summarizing this uncertainty in a single plot.
authors: Department of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1766, USA.
authors: Benjamin D
authors: BD
authors: Redelings
authors: Marc A
authors: MA
authors: Suchard
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001483:Base Sequence; D001499:Bayes Theorem; D002965:Classification / Q000379:methods*; D003198:Computer Simulation; D008390:Markov Chains; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D010802:Phylogeny; D012341:RNA, Ribosomal, 5S / Q000235:genetics; D016415:Sequence Alignment / Q000379:methods*
chemical_list: D012341:RNA, Ribosomal, 5S