On the inference of complex phylogenetic networks by Markov Chain Monte-Carlo.

For various species, high quality sequences and complete genomes are nowadays available for many individuals. This makes data analysis challenging, as methods need not only to be accurate, but also time efficient given the tremendous amount of data to process. In this article, we introduce an efficient method to infer the evolutionary history of individuals under the multispecies coalescent model in networks (MSNC). Phylogenetic networks are an extension of phylogenetic trees that can contain reticulate nodes, which allow to model complex biological events such as horizontal gene transfer, hybridization and introgression. We present a novel way to compute the likelihood of biallelic markers sampled along genomes whose evolution involved such events. This likelihood computation is at the heart of a Bayesian network inference method called SnappNet, as it extends the Snapp method inferring evolutionary trees under the multispecies coalescent model, to networks. SnappNet is available as a package of the well-known beast 2 software. Recently, the MCMC_BiMarkers method, implemented in PhyloNet, also extended Snapp to networks. Both methods take biallelic markers as input, rely on the same model of evolution and sample networks in a Bayesian framework, though using different methods for computing priors. However, SnappNet relies on algorithms that are exponentially more time-efficient on non-trivial networks. Using simulations, we compare performances of SnappNet and MCMC_BiMarkers. We show that both methods enjoy similar abilities to recover simple networks, but SnappNet is more accurate than MCMC_BiMarkers on more complex network scenarios. Also, on complex networks, SnappNet is found to be extremely faster than MCMC_BiMarkers in terms of time required for the likelihood computation. We finally illustrate SnappNet performances on a rice data set. SnappNet infers a scenario that is consistent with previous results and provides additional understanding of rice evolution.

Midazolam sedation in palliative medicine: retrospective study in a French center for cancer control.

BACKGROUND: French legislation about sedation in palliative medicine evolved in 2016 with the introduction of a right to deep and continuous sedation, maintained until death. The objective was to describe midazolam sedation at the COL (Centre Oscar Lambret [Oscar Lambret Center], French regional center for cancer control), in order to establish a current overview before the final legislative changes. METHODS: Descriptive, retrospective and single-center study, concerning major patients in palliative care hospitalized from 01/01/2014 to 12/31/2015, who had been sedated by midazolam. The proven sedations (explicitly named) and the probable sedations were distinguished. RESULTS: A total of 54 sedations were identified (48 proven, 6 probable). Refractory symptoms accounted for 48.1% of indications, complications with immediate risk of death 46.3%, existential suffering 5.6%. Titration was performed in 44.4% of cases. Sedation was continuous until death for 98.1% of the cases. Probable sedation had a higher failure rate than proven sedation. Significant differences existed for the palliative care unit compared to other units regarding information to the patient, their consent, anticipation, mention by correspondence and carrying out titrations. When patients had already been treated with midazolam, the induction doses, initial maintenance doses, and doses at the time of death were significantly higher. For those receiving opioids, the maintenance dose at the time of death was higher. No comparison found a difference in overall survival. CONCLUSIONS: After a sufficient follow-up has enabled teams to familiarize with this new legislation, reflection on sedation should be conducted to adapt to final recommendations.

RecPhyloXML: a format for reconciled gene trees.

Motivation: A reconciliation is an annotation of the nodes of a gene tree with evolutionary events-for example, speciation, gene duplication, transfer, loss, etc.-along with a mapping onto a species tree. Many algorithms and software produce or use reconciliations but often using different reconciliation formats, regarding the type of events considered or whether the species tree is dated or not. This complicates the comparison and communication between different programs. Results: Here, we gather a consortium of software developers in gene tree species tree reconciliation to propose and endorse a format that aims to promote an integrative-albeit flexible-specification of phylogenetic reconciliations. This format, named recPhyloXML, is accompanied by several tools such as a reconciled tree visualizer and conversion utilities. Availability and implementation: http://phylariane.univ-lyon1.fr/recphyloxml/.

REGOSARC: Regorafenib versus placebo in doxorubicin-refractory soft-tissue sarcoma-A quality-adjusted time without symptoms of progression or toxicity analysis.

BACKGROUND: In a placebo-controlled, randomized phase 2 trial (ClinicalTrials.gov identifier NCT01900743), regorafenib improved progression-free survival (PFS) for patients with doxorubicin-pretreated advanced nonadipocytic sarcoma. A quality-adjusted time without symptoms of progression or toxicity (Q-TWiST) post hoc exploratory analysis was applied to provide an integrated measure of its clinical benefit. METHODS: In the base-case analysis, each patient's overall survival (OS) was partitioned into 3 mutually exclusive health states: the time with a grade 3 or 4 adverse event (TOX), the time without symptoms of disease or grade 3 or 4 toxicity from treatment, and the time after tumor progression or relapse. The time spent in each state was weighted with a health-state utility associated with that state and was summed to calculate the Q-TWiST. The stability of the base-case analysis was explored with several sensitivity analyses. RESULTS: In nonadipocytic sarcoma, the PFS was (4.0 months [2.6-5.5 months] with regorafenib vs 1.0 month [0.9-1.8 months] with a placebo; hazard ratio, 0.36 [0.25-0.53]; P < .0001); the OS was 13.4 months (8.6-17.3 months) with regorafenib and 9.0 months (6.8-12.5 months) with a placebo (hazard ratio, 0.67 [0.44-1.02]). With the classic definition of TOX (including all grade 3 and 4 clinical adverse events), the Q-TWiSTs were 8.0 months (7.0-9.0 months) with regorafenib and 5.7 months (4.9-6.4 months) with a placebo (P < .001). CONCLUSIONS: For patients with doxorubicin-pretreated soft-tissue sarcoma, regorafenib significantly improved quality-adjusted survival in comparison with a placebo. Cancer 2017;123:2294-2302. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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.

Inferring gene duplications, transfers and losses can be done in a discrete framework.

In the field of phylogenetics, the evolutionary history of a set of organisms is commonly depicted by a species tree-whose internal nodes represent speciation events-while the evolutionary history of a gene family is depicted by a gene tree-whose internal nodes can also represent macro-evolutionary events such as gene duplications and transfers. As speciation events are only part of the events shaping a gene history, the topology of a gene tree can show incongruences with that of the corresponding species tree. These incongruences can be used to infer the macro-evolutionary events undergone by the gene family. This is done by embedding the gene tree inside the species tree and hence providing a reconciliation of those trees. In the past decade, several parsimony-based methods have been developed to infer such reconciliations, accounting for gene duplications ([Formula: see text]), transfers ([Formula: see text]) and losses ([Formula: see text]). The main contribution of this paper is to formally prove an important assumption implicitly made by previous works on these reconciliations, namely that solving the (maximum) parsimony [Formula: see text] reconciliation problem in the discrete framework is equivalent to finding a most parsimonious [Formula: see text] scenario in the continuous framework. In the process, we also prove several intermediate results that are useful on their own and constitute a theoretical toolbox that will likely facilitate future theoretical contributions in the field.

Ancestral gene synteny reconstruction improves extant species scaffolding.

We exploit the methodological similarity between ancestral genome reconstruction and extant genome scaffolding. We present a method, called ARt-DeCo that constructs neighborhood relationships between genes or contigs, in both ancestral and extant genomes, in a phylogenetic context. It is able to handle dozens of complete genomes, including genes with complex histories, by using gene phylogenies reconciled with a species tree, that is, annotated with speciation, duplication and loss events. Reconstructed ancestral or extant synteny comes with a support computed from an exhaustive exploration of the solution space. We compare our method with a previously published one that follows the same goal on a small number of genomes with universal unicopy genes. Then we test it on the whole Ensembl database, by proposing partial ancestral genome structures, as well as a more complete scaffolding for many partially assembled genomes on 69 eukaryote species. We carefully analyze a couple of extant adjacencies proposed by our method, and show that they are indeed real links in the extant genomes, that were missing in the current assembly. On a reduced data set of 39 eutherian mammals, we estimate the precision and sensitivity of ARt-DeCo by simulating a fragmentation in some well assembled genomes, and measure how many adjacencies are recovered. We find a very high precision, while the sensitivity depends on the quality of the data and on the proximity of closely related genomes.

CompPhy: a web-based collaborative platform for comparing phylogenies.

BACKGROUND: Collaborative tools are of great help in conducting projects involving distant workers. Recent web technologies have helped to build such tools for jointly editing office documents and scientific data, yet none are available for handling phylogenies. Though a large number of studies and projects in evolutionary biology and systematics involve collaborations between scientists of different institutes, current tree comparison visualization software and websites are directed toward single-user access. Moreover, tree comparison functionalities are dispersed between different software that mainly focus on high level single tree visualization but to the detriment of basic tree comparison features. RESULTS: The web platform presented here, named CompPhy, intends to fill this gap by allowing collaborative work on phylogenies and by gathering simple advanced tools dedicated to tree comparison. It offers functionalities for tree edition, tree comparison, supertree inference and data management in a collaborative environment. The latter aspect is a specific feature of the platform, allowing people located in different places to work together at the same time on a common project. CompPhy thus proposes shared tree visualization, both synchronous and asynchronous tree manipulation, data exchange/storage, as well as facilities to keep track of the progress of analyses in working sessions. Specific advanced comparison tools are also available, such as consensus and supertree inference, or automated branch swaps of compared trees. As projects can be readily created and shared, CompPhy is also a tool that can be used easily to interact with students in a educational setting, either in the classroom or for assignments. CONCLUSIONS: CompPhy is the first web platform devoted to the comparison of phylogenetic trees allowing real-time distant collaboration on a phylogenetic/phylogenomic project. This application can be accessed freely with a recent browser at the following page of the ATGC bioinformatics platform: http://www.atgc-montpellier.fr/compphy/ .

Amalgamating source trees with different taxonomic levels.

Supertree methods combine a collection of source trees into a single parent tree or supertree. For almost all such methods, the terminal taxa across the source trees have to be non-nested for the output supertree to make sense. Motivated by Page, the first supertree method for combining rooted source trees where the taxa can be hierarchically nested is called AncestralBuild. In addition to taxa labeling the leaves, this method allows the rooted source trees to have taxa labeling some of the interior nodes at a higher taxonomic level than their descendants (e.g., genera vs. species). However, the utility of AncestralBuild is somewhat restricted as it is mostly intended to decide if a collection of rooted source trees is compatible. If the initial collection is not compatible, then no tree is returned. To overcome this restriction, we introduce here the MultiLevelSupertree (MLS) supertree method whose input is the same as that for AncestralBuild, but which accommodates incompatibilities among rooted source trees using a MinCut-like procedure. We show that MLS has several desirable properties including the preservation of common subtrees among the source trees, the preservation of ancestral relationships whenever they are compatible, as well as running in polynomial time. Furthermore, application to a small test data set (the mammalian carnivore family Phocidae) indicates that the method correctly places nested taxa at different taxonomic levels (reflecting vertical signal), even in cases where the input trees harbor a significant level of conflict between their clades (i.e., in their horizontal signal).

Sequencing of the smallest Apicomplexan genome from the human pathogen Babesia microti.

We have sequenced the genome of the emerging human pathogen Babesia microti and compared it with that of other protozoa. B. microti has the smallest nuclear genome among all Apicomplexan parasites sequenced to date with three chromosomes encoding ∼3500 polypeptides, several of which are species specific. Genome-wide phylogenetic analyses indicate that B. microti is significantly distant from all species of Babesidae and Theileridae and defines a new clade in the phylum Apicomplexa. Furthermore, unlike all other Apicomplexa, its mitochondrial genome is circular. Genome-scale reconstruction of functional networks revealed that B. microti has the minimal metabolic requirement for intraerythrocytic protozoan parasitism. B. microti multigene families differ from those of other protozoa in both the copy number and organization. Two lateral transfer events with significant metabolic implications occurred during the evolution of this parasite. The genomic sequencing of B. microti identified several targets suitable for the development of diagnostic assays and novel therapies for human babesiosis.

Insights Into the Evolution, Virulence and Speciation of Babesia MO1 and Babesia divergens Through Multiomics Analyses.

AbstractBabesiosis, caused by protozoan parasites of the genus Babesia, is an emerging tick-borne disease of significance for both human and animal health. Babesia parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of new Babesia species underscores the ongoing risk of zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental changes. One such pathogen, Babesia MO1, previously implicated in severe cases of human babesiosis in the United States, was initially considered a subspecies of B. divergens, the predominant agent of human babesiosis in Europe. Here we report comparative multiomics analyses of B. divergens and B. MO1 that offer insight into their biology and evolution. Our analysis shows that despite their highly similar genomic sequences, substantial genetic and genomic divergence occurred throughout their evolution resulting in major differences in gene functions, expression and regulation, replication rates and susceptibility to antiparasitic drugs. Furthermore, both pathogens have evolved distinct classes of multigene families, crucial for their pathogenicity and adaptation to specific mammalian hosts. Leveraging genomic information for B. MO1, B. divergens, and other members of the Babesiidae family within Apicomplexa provides valuable insights into the evolution, diversity, and virulence of these parasites. This knowledge serves as a critical tool in preemptively addressing the emergence and rapid transmission of more virulent strains.

Multiomics analysis reveals B. MO1 as a distinct Babesia species and provides insights into its evolution and virulence.

Babesiosis, caused by protozoan parasites of the genus Babesia , is an emerging tick-borne disease of significance for both human and animal health. Babesia parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of various Babesia species underscores the ongoing risk of new zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental shifts impacting the distribution and transmission dynamics of parasites, their vectors, and reservoir hosts. One such species, Babesia MO1, previously implicated in severe cases of human babesiosis in the midwestern United States, was initially considered closely related to B. divergens , the predominant agent of human babesiosis in Europe. Yet, uncertainties persist regarding whether these pathogens represent distinct variants of the same species or are entirely separate species. We show that although both B. MO1 and B. divergens share similar genome sizes, comprising three nuclear chromosomes, one linear mitochondrial chromosome, and one circular apicoplast chromosome, major differences exist in terms of genomic sequence divergence, gene functions, transcription profiles, replication rates and susceptibility to antiparasitic drugs. Furthermore, both pathogens have evolved distinct classes of multigene families, crucial for their pathogenicity and adaptation to specific mammalian hosts. Leveraging genomic information for B. MO1, B. divergens , and other members of the Babesiidae family within Apicomplexa provides valuable insights into the evolution, diversity, and virulence of these parasites. This knowledge serves as a critical tool in preemptively addressing the emergence and rapid transmission of more virulent strains.

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.

Using gamification to improve engagement and learning outcomes in medical microbiology: the case study of 'BacteriaGame'.

The fight against antibiotic resistance has become a true global public health challenge of gargantuan proportions. Amongst the myriad of approaches being explored to tackle this predicament, one strategy involves enhancing prescriber knowledge and in particular their basic knowledge of medical bacteriology. Yet, as we well know in medical microbiology teachings, traditional lectures can be arduous, attempting to cram in a vast array of information in a limited time. An alternative solution to improve student engagement and enhance learning outcomes is to utilize educational games in complementary approach. Such games are an effective means of inspiring students to learn, encouraging self-assessment, and injecting diversity into the teaching process. To this end, we have developed and evaluated an educational card game, the 'BacteriaGame,' aimed at our medical students in medical bacteriology. Designed for students at the basic level, it serves as activity at the end of their apprenticeship to their bacteriology education. Additionally, it can also be used as a review tool by more advanced students, with teachers able to impart additional knowledge as the game progresses. We also use it in continuous training of medical laboratory staff. In this study, we evaluated the game at various stages of medical education, collecting feedback and analysing its impact on knowledge acquisition, comparing it to traditional lectures. Feedback from the majority of students revealed that the rules were clear, the game was enjoyable, and neither too lengthy nor too challenging. The integration of 'BacteriaGame' into their future training piqued their interest. In terms of learning outcomes, we discovered a significant increase in knowledge acquisition among those who used the game (P < .05). 'BacteriaGame' is now published by the French Society of Microbiology (SFM) and distributed in all medical and pharmacy schools thanks to a funding of the French Health Ministry. An English edition of the game is also available for international use as a physical copy to be purchased from the SFM. This will allow a large-scale distribution to colleagues who would like to use this game in their teaching.

ScripTree: scripting phylogenetic graphics.

UNLABELLED: There is a large amount of tools for interactive display of phylogenetic trees. However, there is a shortage of tools for the automation of tree rendering. Scripting phylogenetic graphics would enable the saving of graphical analyses involving numerous and complex tree handling operations and would allow the automation of repetitive tasks. ScripTree is a tool intended to fill this gap. It is an interpreter to be used in batch mode. Phylogenetic graphics instructions, related to tree rendering as well as tree annotation, are stored in a text file and processed in a sequential way. AVAILABILITY: ScripTree can be used online or downloaded at www.scriptree.org, under the GPL license. IMPLEMENTATION: ScripTree, written in Tcl/Tk, is a cross-platform application available for Windows and Unix-like systems including OS X. It can be used either as a stand-alone package or included in a bioinformatic pipeline and linked to a HTTP server.

Computing galled networks from real data.

MOTIVATION: Developing methods for computing phylogenetic networks from biological data is an important problem posed by molecular evolution and much work is currently being undertaken in this area. Although promising approaches exist, there are no tools available that biologists could easily and routinely use to compute rooted phylogenetic networks on real datasets containing tens or hundreds of taxa. Biologists are interested in clades, i.e. groups of monophyletic taxa, and these are usually represented by clusters in a rooted phylogenetic tree. The problem of computing an optimal rooted phylogenetic network from a set of clusters, is hard, in general. Indeed, even the problem of just determining whether a given network contains a given cluster is hard. Hence, some researchers have focused on topologically restricted classes of networks, such as galled trees and level-k networks, that are more tractable, but have the practical draw-back that a given set of clusters will usually not possess such a representation. RESULTS: In this article, we argue that galled networks (a generalization of galled trees) provide a good trade-off between level of generality and tractability. Any set of clusters can be represented by some galled network and the question whether a cluster is contained in such a network is easy to solve. Although the computation of an optimal galled network involves successively solving instances of two different NP-complete problems, in practice our algorithm solves this problem exactly on large datasets containing hundreds of taxa and many reticulations in seconds, as illustrated by a dataset containing 279 prokaryotes. AVAILABILITY: We provide a fast, robust and easy-to-use implementation of this work in version 2.0 of our tree-handling software Dendroscope, freely available from http://www.dendroscope.org.

PhyloExplorer: a web server to validate, explore and query phylogenetic trees.

BACKGROUND: Many important problems in evolutionary biology require molecular phylogenies to be reconstructed. Phylogenetic trees must then be manipulated for subsequent inclusion in publications or analyses such as supertree inference and tree comparisons. However, no tool is currently available to facilitate the management of tree collections providing, for instance: standardisation of taxon names among trees with respect to a reference taxonomy; selection of relevant subsets of trees or sub-trees according to a taxonomic query; or simply computation of descriptive statistics on the collection. Moreover, although several databases of phylogenetic trees exist, there is currently no easy way to find trees that are both relevant and complementary to a given collection of trees. RESULTS: We propose a tool to facilitate assessment and management of phylogenetic tree collections. Given an input collection of rooted trees, PhyloExplorer provides facilities for obtaining statistics describing the collection, correcting invalid taxon names, extracting taxonomically relevant parts of the collection using a dedicated query language, and identifying related trees in the TreeBASE database. CONCLUSION: PhyloExplorer is a simple and interactive website implemented through underlying Python libraries and MySQL databases. It is available at: http://www.ncbi.orthomam.univ-montp2.fr/phyloexplorer/ and the source code can be downloaded from: http://code.google.com/p/taxomanie/.

PhySIC_IST: cleaning source trees to infer more informative supertrees.

BACKGROUND: Supertree methods combine phylogenies with overlapping sets of taxa into a larger one. Topological conflicts frequently arise among source trees for methodological or biological reasons, such as long branch attraction, lateral gene transfers, gene duplication/loss or deep gene coalescence. When topological conflicts occur among source trees, liberal methods infer supertrees containing the most frequent alternative, while veto methods infer supertrees not contradicting any source tree, i.e. discard all conflicting resolutions. When the source trees host a significant number of topological conflicts or have a small taxon overlap, supertree methods of both kinds can propose poorly resolved, hence uninformative, supertrees. RESULTS: To overcome this problem, we propose to infer non-plenary supertrees, i.e. supertrees that do not necessarily contain all the taxa present in the source trees, discarding those whose position greatly differs among source trees or for which insufficient information is provided. We detail a variant of the PhySIC veto method called PhySIC_IST that can infer non-plenary supertrees. PhySIC_IST aims at inferring supertrees that satisfy the same appealing theoretical properties as with PhySIC, while being as informative as possible under this constraint. The informativeness of a supertree is estimated using a variation of the CIC (Cladistic Information Content) criterion, that takes into account both the presence of multifurcations and the absence of some taxa. Additionally, we propose a statistical preprocessing step called STC (Source Trees Correction) to correct the source trees prior to the supertree inference. STC is a liberal step that removes the parts of each source tree that significantly conflict with other source trees. Combining STC with a veto method allows an explicit trade-off between veto and liberal approaches, tuned by a single parameter.Performing large-scale simulations, we observe that STC+PhySIC_IST infers much more informative supertrees than PhySIC, while preserving low type I error compared to the well-known MRP method. Two biological case studies on animals confirm that the STC preprocess successfully detects anomalies in the source trees while STC+PhySIC_IST provides well-resolved supertrees agreeing with current knowledge in systematics. CONCLUSION: The paper introduces and tests two new methodologies, PhySIC_IST and STC, that demonstrate the interest in inferring non-plenary supertrees as well as preprocessing the source trees. An implementation of the methods is available at: http://www.atgc-montpellier.fr/physic_ist/.

One fig to bind them all: host conservatism in a fig wasp community unraveled by cospeciation analyses among pollinating and nonpollinating fig wasps.

The study of chalcid wasps that live within syconia of fig trees (Moraceae, Ficus), provides a unique opportunity to investigate the evolution of specialized communities of insects. By conducting cospeciation analyses between figs of section Galoglychia and some of their associated fig wasps, we show that, although host switches and duplication have evidently played a role in the construction of the current associations, the global picture is one of significant cospeciation throughout the evolution of these communities. Contrary to common belief, nonpollinating wasps are at least as constrained as pollinators by their host association in their diversification in this section. By adapting a randomization test in a supertree context, we further confirm that wasp phylogenies are significantly congruent with each other, and build a "wasp community" supertree that retrieves Galoglychia taxonomic subdivisions. Altogether, these results probably reflect wasp host specialization but also, to some extent, they might indicate that niche saturation within the fig prevents recurrent intrahost speciation and host switching. Finally, a comparison of ITS2 sequence divergence of cospeciating pairs of wasps suggests that the diversification of some pollinating and nonpollinating wasps of Galoglychia figs has been synchronous but that pollinating wasps exhibit a higher rate of molecular evolution.

A geography-aware reconciliation method to investigate diversification patterns in host/parasite interactions.

Cospeciation studies aim at investigating whether hosts and symbionts speciate simultaneously or whether the associations diversify through host shifts. This problem is often tackled through reconciliation analyses that map the symbiont phylogeny onto the host phylogeny by mixing different types of diversification events. These reconciliations can be difficult to interpret and are not always biologically realistic. Researchers have underlined that the biogeographic histories of both hosts and symbionts influence the probability of cospeciation and host switches, but up to now no reconciliation software integrates geographic data. We present a new functionality in the Mowgli software that bridges this gap. The user can provide geographic information on both the host and symbiont extant and ancestral taxa. Constraints in the reconciliation algorithm have been implemented to generate biologically realistic codiversification scenarios. We apply our method to the fig/fig wasp association and infer diversification scenarios that differ from reconciliations ignoring geographic information. In addition, we updated the reconciliation viewer SylvX to visualize ancestral character states on the phylogenetic trees and highlight parts of reconciliations that are geographically inconsistent when not accounting for geographic constraints. We suggest that the comparison of reconciliations obtained with and without such constraints can help solving ambiguities in the biogeographic histories of the partners. With the development of robust methods in historical biogeography, and the advent of next-generation sequencing that leads to better-resolved trees, a geography-aware reconciliation method represents a substantial advance that is likely to be useful to researchers studying the evolution of biotic interactions and biogeography.