Published online 3 November 2007 Nucleic Acids Research, 2008, Vol. 36, Database issue D787–D792 doi:10.1093/nar/gkm878 Evola: Ortholog database of all human genes in H-InvDB with manual curation of phylogenetic trees Akihiro Matsuya1,2, Ryuichi Sakate1,3,*, Yoshihiro Kawahara1,3, Kanako O. Koyanagi4, Yoshiharu Sato1,3, Yasuyuki Fujii1,3, Chisato Yamasaki1,3, Takuya Habara1,3, Hajime Nakaoka5, Fusano Todokoro1,6, Kaori Yamaguchi1,3, Toshinori Endo4, Satoshi OOta7, Wojciech Makalowski8, Kazuho Ikeo9, Yoshiyuki Suzuki9, Kousuke Hanada9, Katsuyuki Hashimoto10, Momoki Hirai11, Hisakazu Iwama12, Naruya Saitou13, Aiko T. Hiraki1,3, Lihua Jin9, Yayoi Kaneko1,3, Masako Kanno1,3, Katsuhiko Murakami1,3, Akiko Ogura Noda1,3, Naomi Saichi1,3, Ryoko Sanbonmatsu1,3, Mami Suzuki1,3, Jun-ichi Takeda1,3, Masayuki Tanaka1,3, Takashi Gojobori3,9, Tadashi Imanishi3 and Takeshi Itoh3,14 1Integrated Database Group, Japan Biological Information Research Center, Japan Biological Informatics Consortium, 2Government & Public Corporation Information Systems, Hitachi, Co., Ltd., 3Integrated Database Group, Biological Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, 4Graduate School of Information Science and Technology, Hokkaido University, Hokkaido, 5C’s Lab Co., Ltd., Hokkaido, 6DYNACOM Co., Ltd, Chiba, 7BioResource Center, RIKEN, Ibaraki, Japan, 8Institute of Bioinformatics, University of Muenster, Muenster, Germany, 9Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Shizuoka, 10Department of Biomedical Resources, National Institute of Biomedical Innovation, Osaka, 11International Research and Educational Institute for Integrated Medical Sciences, Tokyo Women’s Medical University, Tokyo, 12Kagawa University, Kagawa, 13Department of Population Genetics, National Institute of Genetics, Shizuoka and 14Division of Genome and Biodiversity Research, National Institute of Agrobiological Sciences, Ibaraki, Japan Received August 15, 2007; Revised September 27, 2007; Accepted October 1, 2007 ABSTRACT Orthologs are genes in different species that evolved from a common ancestral gene by specia- tion. Currently, with the rapid growth of transcrip- tome data of various species, more reliable orthology information is prerequisite for further studies. However, detection of orthologs could be erroneous if pairwise distance-based methods, such as reciprocal BLAST searches, are utilized. Thus, as a sub-database of H-InvDB, an integrated database of annotated human genes (http://h-invi tational.jp/), we constructed a fully curated data- base of evolutionary features of human genes, called ‘Evola’. In the process of the ortholog detection, computational analysis based on con- served genome synteny and transcript sequence similarity was followed by manual curation by researchers examining phylogenetic trees. In total, 18 968 human genes have orthologs among 11 vertebrates (chimpanzee, mouse, cow, chicken, zebrafish, etc.), either computationally detected or manually curated orthologs. Evola provides amino acid sequence alignments and phylogenetic trees of orthologs and homologs. In ‘dN/dS view’, natural selection on genes can be analyzed between human and other species. In ‘Locus maps’, all transcript variants and their exon/intron structures can be compared among orthologous gene loci. We expect the Evola to serve as a comprehensive and reliable database to be utilized in comparative analyses for obtaining new knowledge about human genes. Evola is available at http://www.h-invitational.jp/ evola/. INTRODUCTION A large number of genome and transcript sequences accumulated in the last decade give us an opportunity *To whom correspondence should be addressed. Tel: +81 3 3599 8800; Fax: +81 3 3599 8801; Email: rsakate@ni.aist.go.jp 2007 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.