Jean-Philippe Doyon

Models, algorithms and programs for phylogeny reconciliation

Gene sequences contain a gold mine of phylogenetic information. But unfortunately for taxonomists this information does not only tell the story of the species from which it was collected. Genes have their own complex histories which record speciation events, of course, but also many other events. Among them, gene duplications, transfers and losses are especially important to identify. These events are crucial to account for when reconstructing the history of species, and they play a fundamental role in the evolution of genomes, the diversification of organisms and the emergence of new cellular functions. We review reconciliations between gene and species trees, which are rigorous approaches for identifying duplications, transfers and losses that mark the evolution of a gene family. Existing reconciliation models and algorithms are reviewed and difficulties in modeling gene transfers are discussed. We also compare different reconciliation programs along with their advantages and disadvantages.

Gene family evolution by duplication, speciation, and loss.

We consider two algorithmic questions related to the evolution of gene families. First, given a gene tree for a gene family, can the evolutionary history of this family be explained with only speciation and duplication events? Such gene trees are called DS-trees. We show that this question can be answered in linear time, and that a DS-tree induces a single species tree. We then study a natural extension of this problem: what is the minimum number of gene losses involved in an evolutionary history leading to an observed gene tree or set of gene trees? Based on our characterization of DS-trees, we propose a heuristic for this problem, and evaluate it on a dataset of plants gene families and on simulated data.

An Efficient Method for Exploring the Space of Gene Tree/Species Tree Reconciliations in a Probabilistic Framework

Background. Inferring an evolutionary scenario for a gene family is a fundamental problem with applications both in functional and evolutionary genomics. The gene tree/species tree reconciliation approach has been widely used to address this problem, but mostly in a discrete parsimony framework that aims at minimizing the number of gene duplications and/or gene losses. Recently, a probabilistic approach has been developed, based on the classical birth-and-death process, including efficient algorithms for computing posterior probabilities of reconciliations and orthology prediction. Results. In previous work, we described an algorithm for exploring the whole space of gene tree/species tree reconciliations, that we adapt here to compute efficiently the posterior probability of such reconciliations. These posterior probabilities can be either computed exactly or approximated, depending on the reconciliation space size. We use this algorithm to analyze the probabilistic landscape of the space of reconciliations for a real data set of fungal gene families and several data sets of synthetic gene trees. Conclusion. The results of our simulations suggest that, with exact gene trees obtained by a simple birth-and-death process and realistic gene duplication/loss rates, a very small subset of all reconciliations needs to be explored in order to approximate very closely the posterior probability of the most likely reconciliations. For cases where the posterior probability mass is more evenly dispersed, our method allows to explore efficiently the required subspace of reconciliations.

Space of gene/species trees reconciliations and parsimonious models.

We describe algorithms to study the space of all possible reconciliations between a gene tree and a species tree, that is counting the size of this space, uniformly generate a random reconciliation, and exploring this space in optimal time using combinatorial operators. We also extend these algorithms for optimal and sub-optimal reconciliations according to the three usual combinatorial costs (duplication, loss, and mutation). Applying these algorithms to simulated and real gene family evolutionary scenarios, we observe that the LCA (Last Common Ancestor) based reconciliation is almost always identical to the real one.

Reconciliation and local gene tree rearrangement can be of mutual profit

BackgroundReconciliation methods compare gene trees and species trees to recover evolutionary events such as duplications, transfers and losses explaining the history and composition of genomes. It is well-known that gene trees inferred from molecular sequences can be partly erroneous due to incorrect sequence alignments as well as phylogenetic reconstruction artifacts such as long branch attraction. In practice, this leads reconciliation methods to overestimate the number of evolutionary events. Several methods have been proposed to circumvent this problem, by collapsing the unsupported edges and then resolving the obtained multifurcating nodes, or by directly rearranging the binary gene trees. Yet these methods have been defined for models of evolution accounting only for duplications and losses, i.e. can not be applied to handle prokaryotic gene families.ResultsWe propose a reconciliation method accounting for gene duplications, losses and horizontal transfers, that specifically takes into account the uncertainties in gene trees by rearranging their weakly supported edges. Rearrangements are performed on edges having a low confidence value, and are accepted whenever they improve the reconciliation cost. We prove useful properties on the dynamic programming matrix used to compute reconciliations, which allows to speed-up the tree space exploration when rearrangements are generated by Nearest Neighbor Interchanges (NNI) edit operations. Experiments on synthetic data show that gene trees modified by such NNI rearrangements are closer to the correct simulated trees and lead to better event predictions on average. Experiments on real data demonstrate that the proposed method leads to a decrease in the reconciliation cost and the number of inferred events. Finally on a dataset of 30 k gene families, this reconciliation method shows a ranking of prokaryotic phyla by transfer rates identical to that proposed by a different approach dedicated to transfer detection [BMCBIOINF 11:324, 2010, PNAS 109(13):4962–4967, 2012].ConclusionsProkaryotic gene trees can now be reconciled with their species phylogeny while accounting for the uncertainty of the gene tree. More accurate and more precise reconciliations are obtained with respect to previous parsimony algorithms not accounting for such uncertainties [LNCS 6398:93–108, 2010, BIOINF 28(12): i283–i291, 2012].A software implementing the method is freely available at http://www.atgc-montpellier.fr/Mowgli/.

Accounting for gene tree uncertainties improves gene trees and reconciliation inference

We propose a reconciliation heuristic accounting for gene duplications, losses and horizontal transfers that specifically takes into account the uncertainties in the gene tree. Rearrangements are tried for gene tree edges that are weakly supported, and are accepted whenever they improve the reconciliation cost. We prove useful properties on the dynamic programming matrix used to compute reconciliations, which al- lows to speed-up the tree space exploration when rearrangements are generated by Nearest Neighbor Interchanges (NNI) edit operations. Experimental results on simulated and real data confirm that running times are greatly reduced when considering the above-mentioned optimization in comparison to the naive rearrangement procedure. Results also show that gene trees modified by such NNI rearrangements are closer to the correct (simulated) trees and lead to more correct event predictions on average. The program is available at http://www.atgc-montpellier.fr/Mowgli/We propose a reconciliation heuristic accounting for gene duplications, losses and horizontal transfers that specifically takes into account the uncertainties in the gene tree. Rearrangements are tried for gene tree edges that are weakly supported, and are accepted whenever they improve the reconciliation cost. We prove useful properties on the dynamic programming matrix used to compute reconciliations, which allows to speed-up the tree space exploration when rearrangements are generated by Nearest Neighbor Interchanges (NNI) edit operations. Experimental results on simulated and real data confirm that running times are greatly reduced when considering the above-mentioned optimization in comparison to the naive rearrangement procedure. Results also show that gene trees modified by such NNI rearrangements are closer to the correct (simulated) trees and lead to more correct event predictions on average. The program is available at http://www.atgc-montpellier.fr/Mowgli/

Branch-and-Bound Approach for Parsimonious Inference of a Species Tree from a Set of Gene Family Trees

We describe a Branch-and-Bound algorithm for computing a parsimonious species tree, given a set of gene family trees. Our algorithm can consider three cost measures: number of gene duplications, number of gene losses, and both combined. Moreover, to cope with intrinsic limitations of Branch-and-Bound algorithms for species trees inference regarding the number of taxa that can be considered, our algorithm can naturally take into account predefined relationships between sets of taxa. We test our algorithm on a dataset of eukaryotic gene families spanning 29 taxa.

SylvX: a viewer for phylogenetic tree reconciliations.

MOTIVATION Reconciliation methods aim at recovering the evolutionary processes that shaped the history of a given gene family including events such as duplications, transfers and losses by comparing the discrepancies between the topologies of the associated gene and species trees. These methods are also used in the framework of host/parasite studies to recover co-diversification scenarios including co-speciation events, host-switches and extinctions. These evolutionary processes can be graphically represented as nested trees. These interconnected graphs can be visually messy and hard to interpret, and despite the fact that reconciliations are increasingly used, there is a shortage of tools dedicated to their graphical management. Here we present SylvX, a reconciliation viewer which implements classical phylogenetic graphic operators (swapping, highlighting, etc.) and new methods to ease interpretation and comparison of reconciliations (multiple maps, moving, shrinking sub-reconciliations). AVAILABILITY AND IMPLEMENTATION SylvX is an open source, cross-platform, standalone editor available for Windows and Unix-like systems including OSX. It is publicly available at www.sylvx.org.

Algorithms for Exploring the Space of Gene Tree/Species Tree Reconciliations

We describe algorithms to explore the space of all possible reconciliations between a gene tree and a species tree. We propose an algorithm for generating a random reconciliation, and combinatorial operators and algorithms to explore the space of all possible reconciliations between a gene tree and a species tree in optimal time. We apply these algorithms to simulated data.

Inferring a Duplication, Speciation and Loss History from a Gene Tree (Extended Abstract)

We consider two questions related to the evolution of gene families. First, given a gene tree for a gene family, can the evolutionary history of this family be explained with only speciation and duplication events, and without gene loss. We show that this question can be answered in linear time, and that such a gene tree induces a single species tree consistent with a history with no loss. We then present a heuristic for the following problem: if a gene tree can not be explained without gene loss, what is the minimum number of losses involved in an evolutionary history of the gene family. We finally evaluate our algorithms on a dataset of plants gene families.