Published online 16 November 2010 Nucleic Acids Research, 2011, Vol. 39, Database issue D569–D575 doi:10.1093/nar/gkq1013 PhEVER: a database for the global exploration of virus–host evolutionary relationships Leonor Palmeira1,2,3,4,5,*, Simon Penel1,5, Vincent Lotteau5,6,7, Chantal Rabourdin-Combe5,6,7 and Christian Gautier1,2,3,5 1CNRS, UMR5558, Laboratoire de Biome´ trie et Biologie E´ volutive, 2PRABI, P oˆle Rhoˆ ne-Alpes de Bioinformatique, F-69622, Villeurbanne, 3BAMBOO Team, INRIA Rhoˆ ne-Alpes, F-38330, Montbonnot Saint- Martin, France, 4Immunologie-Vaccinologie (B43b), De´ partement des Maladies Infectieuses et Parasitaires, Faculte´ de Me´ decine Ve´ te´ rinaire, Universite´ de Lie` ge, B-4000, Lie` ge, Belgique, 5Universite´ de Lyon, Universite´ Lyon 1, F-69000, 6INSERM, U851 and 7IFR128, F-69007, Lyon, France Received August 14, 2010; Revised October 7, 2010; Accepted October 8, 2010 ABSTRACT Fast viral adaptation and the implication of this rapid evolution in the emergence of several new infec- tious diseases have turned this issue into a major challenge for various research domains. Indeed, viruses are involved in the development of a wide range of pathologies and understanding how viruses and host cells interact in the context of adaptation remains an open question. In order to provide insights into the complex interactions between viruses and their host organisms and namely in the acquisition of novel functions through exchanges of genetic material, we de- veloped the PhEVER database. This database aims at providing accurate evolutionary and phylogenetic information to analyse the nature of virus–virus and virus–host lateral gene transfers. PhEVER (http:// pbil.univ-lyon1.fr/databases/phever) is a unique database of homologous families both (i) between sequences from different viruses and (ii) between viral sequences and sequences from cellular organ- isms. PhEVER integrates extensive data from up-to-date completely sequenced genomes (2426 non-redundant viral genomes, 1007 non-redundant prokaryotic genomes, 43 eukaryotic genomes ranging from plants to vertebrates) and offers a clustering of proteins into homologous families con- taining at least one viral sequences, as well as align- ments and phylogenies for each of these families. Public access to PhEVER is available through its webpage and through all dedicated ACNUC retrieval systems. INTRODUCTION Viruses are responsible for a large number of infectious diseases and cancers. Recently, new viral diseases have emerged leading to severe consequences on human activities. The emergence of many of these new viruses can be attributed to recombining viruses as well as to host species jump (1–3). Therefore, understanding how viruses interact with their hosts and more speciﬁcally how the complex interactions between viruses and their host organisms are acquired and maintained throughout evolution, remains a major challenge (4–7). In order to assess this question, it is of prime importance to be able to detect and quantify the occurrence of lateral gene transfer events, and the impact of these events on viral– host co-evolution. Indeed, the mechanisms behind fast viral adaptation are far from being elucidated. Thus, we developed a global approach aimed at providing accurate evolutionary and phylogenetic information to tackle these questions. The major drawback of currently available databases of homologous families to the study of viral homologies and lateral gene transfer in viruses is their taxonomic compartimentalization. Indeed, current databases present families of homologies either restricted to viruses only [Protein Clusters (8), GeneTree (9)] or to viral taxonomic groups [Viral Orthologous Cluster (10)], some also not presenting viral information [HomoloGene (11)]. The few databases that do present viral and non-viral se- quences, such as Pfam (12) or the Conserved Domain Database (13) do not provide complete phylogenetic trees. This translates into the fact that it is not cur- rently possible to have a global view on viral–host lateral gene transfers due to the difﬁculty of obtaining global information on cross-taxa transfers at the viral level. *To whom correspondence should be addressed. Tel: +32 4 366 42 69; Fax: +32 4 366 42 61; Email: mlpalmeira@ulg.ac.be The Author(s) 2010. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.