MotivationsGene trees inferred solely from multiple alignments of homologous sequences often contain weakly supported and uncertain branches. Information for their full resolution may lie in the dependency between gene families and their genomic context. Integrative methods, using species tree information in addition to sequence information, often rely on a computationally intensive tree space search which forecloses an application to large genomic databases.ResultsWe propose a new method, called ProfileNJ, that takes a gene tree with statistical supports on its branches, and corrects its weakly supported parts by using a combination of information from a species tree and a distance matrix. Its low running time enabled us to use it on the whole Ensembl Compara database, for which we propose an alternative, arguably more plausible set of gene trees. This allowed us to perform a genome-wide analysis of duplication and loss patterns on the history of 63 eukaryote species, and predict ancestral gene content and order for all ancestors along the phylogeny.AvailabilityA web interface called RefineTree, including ProfileNJ as well as a other gene tree correction methods, which we also test on the Ensembl gene families, is available at: http://www-ens.iro.umontreal.ca/~adbit/polytomysolver.html. The code of ProfileNJ as well as the set of gene trees corrected by ProfileNJ from Ensembl Compara version 73 families are also made available.

Abstract. The evolution of genomes can be studied at at least three different scales: the nucleotide level, accounting for substitutions and indels, the gene level, accounting for gains and losses, and the genome level, accounting for rearrangements of chromosome organization. While the nucleotide and gene levels are now often integrated in a single model using reconciled gene trees, very little work integrates the genome level as well, and considers gene trees and gene orders simultaneously. In a seminal book chapter published in 2000 and entitled "Duplication, Rearrangement and Reconciliation", Sankoff and El-Mabrouk outlined a general approach, making a step in that direction. This avenue has been poorly exploited by the community for over ten years, but recent developments allow the design of integrated methods where phylogeny informs the study of synteny and vice-versa. We review these developments and show how this influence of synteny on gene tree construction can be implemented.

BackgroundReconciled gene trees yield orthology and paralogy relationships between genes. This information may however contradict other information on orthology and paralogy provided by other footprints of evolution, such as conserved synteny.ResultsWe explore a way to include external information on orthology in the process of gene tree construction. Given an initial gene tree and a set of orthology constraints on pairs of genes or on clades, we give polynomial-time algorithms for producing a modified gene tree satisfying the set of constraints, that is as close as possible to the original one according to the Robinson-Foulds distance. We assess the validity of the modifications we propose by computing the likelihood ratio between initial and modified trees according to sequence alignments on Ensembl trees, showing that often the two trees are statistically equivalent.AvailabilitySoftware and data available upon request to the corresponding author.

BackgroundMost models of genome evolution concern either genetic sequences, gene content or gene order. They sometimes integrate two of the three levels, but rarely the three of them. Probabilistic models of gene order evolution usually have to assume constant gene content or adopt a presence/absence coding of gene neighborhoods which is blind to complex events modifying gene content.ResultsWe propose a probabilistic evolutionary model for gene neighborhoods, allowing genes to be inserted, duplicated or lost. It uses reconciled phylogenies, which integrate sequence and gene content evolution. We are then able to optimize parameters such as phylogeny branch lengths, or probabilistic laws depicting the diversity of susceptibility of syntenic regions to rearrangements. We reconstruct a structure for ancestral genomes by optimizing a likelihood, keeping track of all evolutionary events at the level of gene content and gene synteny. Ancestral syntenies are associated with a probability of presence.We implemented the model with the restriction that at most one gene duplication separates two gene speciations in reconciled gene trees. We reconstruct ancestral syntenies on a set of 12 drosophila genomes, and compare the evolutionary rates along the branches and along the sites. We compare with a parsimony method and find a significant number of results not supported by the posterior probability. The model is implemented in the Bio++ library. It thus benefits from and enriches the classical models and methods for molecular evolution.