Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd2778910.32607/actanaturae.27789Research ArticlesЭкспериментальные статьиResearch ArticleCOGcollator 2.0: a tool for analyzing distant evolutionary relationships among families of homologous proteinsCOGcollator 2.0: инструмент для анализа далеких родственных связей между семействами гомологичных белковDibrovaD. V.ДиброваД. В.
Russian Federation

School of Bioengineering and Bioinformatics

факультет биоинженерии и биоинформатики

udavdasha@belozersky.msu.ruRykovS. Y.РыковС. Ю.
Russian Federation
udavdasha@belozersky.msu.ruLomonosov Moscow State University, Belozersky Institute of Physico-Chemical BiologyМосковский государственный университет имени М.В. Ломоносова, НИИ физико-химической биологии имени А.Н. БелозерскогоLomonosov Moscow State UniversityМосковский государственный университет имени М.В. ЛомоносоваInstitute of Philosophy, Russian Academy of SciencesИнститут философии РАН2307202618245531409202518112025Copyright ©; 2026, Dibrova D.V., Rykov S.Y.Copyright ©; 2026, Диброва Д.В., Рыков С.Ю.2026Dibrova D.V., Rykov S.Y.Диброва Д.В., Рыков С.Ю.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/27789

The analysis of protein evolutionary relationships is of both theoretical and practical significance. Identifying and characterizing evolutionary relationships between the components of protein complexes and metabolic enzymes fosters a deeper understanding of their evolutionary history and molecular evolution. The existence of related enzymes makes the annotation of new sequences complicated, since this process relies heavily on accurately determining the protein family classification of the sequence being analyzed. Clusters of Orthologous Groups (COGs) are widely used for the classification of prokaryotic proteins. COGs are constructed based on the occurrence of the respective protein-coding genes within complete genomes. Previously, we introduced COGcollator, a tool designed to visualize the relatedness between COGs by analyzing the hits of their profile HMMs (Hidden Markov Models). This paper presents an update of the COGcollator web service. It is based on the latest version of the COG database and features a completely new interface and additional functionalities. To demonstrate the capabilities of our tool and the validity of the data, we present the COGcollator results for the subunits of NADH:quinone oxidoreductase type 1 (NDH-1), a homologue of the mitochondrial complex I, as the evolutionary relationships of NDH-1 with other protein complexes have been extensively documented in the literature. The web service is available free of charge without registration at https://boabio.belozersky.msu.ru/en/COGcollator. Through the web service interface, users can access pre-calculated COGcollator results for 4,972 COGs and download their respective profile HMMs.

Анализ родственных связей между белками интересен как с теоретической, так и с практической стороны. Обнаружение и описание родственных связей между компонентами белковых комплексов и ферментов метаболических путей позволяют лучше понять их эволюционную историю и эволюцию на молекулярном уровне. Существование родственных ферментов затрудняет правильную аннотацию новых последовательностей, во многом зависящую от корректности выделения семейств белков, с которыми соотносится изучаемая последовательность. В биоинформатике широко применяется способ классификации белков прокариот с помощью Кластеров Ортологичных Групп (КОГов), построенных с учетом встречаемости генов соответствующих белков в полных геномах. Ранее нами был предложен COGcollator – инструмент для визуализации степени родства КОГов между собой на основании анализа находок соответствующих им математических моделей (профильных HMM). В этой работе представлено обновление инструмента COGcollator в виде веб-сервиса, соответствующее последней версии базы данных КОГов, с полностью новым интерфейсом и дополнительными функциями. Для демонстрации возможностей нашего инструмента и адекватности данных представлены результаты COGcollator для субъединиц гомолога митохондриального комплекса I, NADH:хинон-оксидоредуктазы типа 1, эволюционные связи которого с другими белковыми комплексами подробно описаны в литературе. Веб-сервис доступен без регистрации по адресу: https://boabio.belozersky.msu.ru/COGcollator. Через интерфейс веб-сервиса можно получить доступ к заранее посчитанным результатам COGcollator для 4972 КОГов, а также скачать профильные HMM для них.

clusters of orthologous groupsCOGphylogenomic analysisweb serverprotein domain structureкластеры ортологичных группCOGфилогеномный анализвеб-сервисдоменная структура белковGovernment of the Russian FederationПравительство РФDmitry Zimin Dynasty FoundationФонд Дмитрия Зимина «Династия»Russian Science FoundationРоссийский научный фонд14–50–00029This study was conducted under the state assignment of Lomonosov Moscow State University. The development of the initial version of the COGcollator tool and its theoretical framework was conducted in 2014–2016 with the support of the Dmitry Zimin Dynasty Foundation. The development of the first version of the COGcollator 1.0 web server was supported by the Russian Science Foundation (RSF, grant no. 14–50–00029).Исследование выполнено в рамках государственного задания МГУ имени М.В. Ломоносова. Разработка исходной версии инструмента COGcollator и его теоретической основы осуществлялась в 2014–2016 гг. при поддержке фонда Дмитрия Зимина «Династия». Разработка первой версии веб-сервера COGcollator 1.0 была поддержана РНФ (грант 14–50–00029).Koonin EV. An apology for orthologs - or brave new memes. Genome Biol. 2001;2(4):comment1005. doi: 10.1186/gb-2001-2-4-comment1005Koonin EV. An apology for orthologs — or brave new memes. Genome Biol. 2001;2(4):comment1005.1–comment1005.2. doi: 10.1186/gb-2001-2-4-comment1005Koonin EV, Makarova KS, Aravind L. Horizontal gene transfer in prokaryotes: quantification and classification. Annu Rev Microbiol. 2001;55:709-742. doi: 10.1146/annurev.micro.55.1.709Arnold BJ, Huang IT, Hanage WP. Horizontal gene transfer and adaptive evolution in bacteria. Nat Rev Microbiol. 2022;20(4):206-218. doi: 10.1038/s41579-021-00650-4Tatusov RL, Koonin EV, Lipman DJ. A genomic perspective on protein families. Science. 1997;278(5338):631-637. doi: 10.1126/science.278.5338.631Kristensen DM, Kannan L, Coleman MK, et al. A low-polynomial algorithm for assembling clusters of orthologous groups from intergenomic symmetric best matches. Bioinformatics. 2010;26(12):1481-1487. doi: 10.1093/bioinformatics/btq229Galperin MY, Makarova KS, Wolf YI, Koonin EV. Expanded microbial genome coverage and improved protein family annotation in the COG database. Nucleic Acids Res. 2015;43(Database issue):D261-D269. doi: 10.1093/nar/gku1223Galperin MY, Wolf YI, Makarova KS, Vera Alvarez R, Landsman D, Koonin EV. COG database update: focus on microbial diversity, model organisms, and widespread pathogens. Nucleic Acids Res. 2021;49(D1):D274-D281. doi: 10.1093/nar/gkaa1018Galperin MY, Wolf YI, Makarova KS, et al. COG database update: focus on microbial diversity, model organisms, and widespread pathogens. Nucleic Acids Res. 2021;49(D1):D274-D281. doi: 10.1093/nar/gkaa1018Galperin MY, Vera Alvarez R, Karamycheva S, et al. COG database update 2024. Nucleic Acids Res. 2024;53(D1):D356–D363. doi: 10.1093/nar/gkae983Galperin MY, Alvarez RV, Karamycheva S, et al. COG database update 2024. Nucleic Acids Res. 2024;53(D1):D356–D363. doi: 10.1093/nar/gkae983Hernández-Plaza A, Szklarczyk D, Botas J, et al. eggNOG 6.0: enabling comparative genomics across 12 535 organisms. Nucleic Acids Res. 2023;51(D1):D389-D394. doi: 10.1093/nar/gkac1022Hernandez-Plaza A, Szklarczyk D, Botas J, et al. eggNOG 6.0: enabling comparative genomics across 12 535 organisms. Nucleic Acids Res. 2023;51(D1):D389-D394. doi: 10.1093/nar/gkac1022Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28(1):27-30. doi: 10.1093/nar/28.1.27Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023;51(D1):D587-D592. doi: 10.1093/nar/gkac963Kanehisa M, Furumichi M, Sato Y, et al. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023;51(D1):D587-D592. doi: 10.1093/nar/gkac963Dibrova DV, Konovalov KA, Perekhvatov VV, Skulachev KV, Mulkidjanian AY. COGcollator: a web server for analysis of distant relationships between homologous protein families. Biol Direct. 2017;12(1):29. doi: 10.1186/s13062-017-0198-xDibrova DV, Konovalov KA, Perekhvatov VV, et al. COGcollator: a web server for analysis of distant relationships between homologous protein families. Biol Direct. 2017;12(1):29. doi: 10.1186/s13062-017-0198-xGogarten JP, Kibak H, Dittrich P, et al. Evolution of the vacuolar H+-ATPase: implications for the origin of eukaryotes. Proc Natl Acad Sci U S A. 1989;86(17):6661-6665. doi: 10.1073/pnas.86.17.6661Gogarten JP, Kibak H, Dittrich P, et al. Evolution of the vacuolar H+-ATPase: implications for the origin of eukaryotes. Proc Natl Acad Sci USA. 1989;86(17):6661-6665. doi: 10.1073/pnas.86.17.6661Wang J, Chitsaz F, Derbyshire MK, et al. The conserved domain database in 2023. Nucleic Acids Res. 2023;51(D1):D384-D388. doi: 10.1093/nar/gkac1096Mistry J, Chuguransky S, Williams L, et al. Pfam: The protein families database in 2021. Nucleic Acids Res. 2021;49(D1):D412-D419. doi: 10.1093/nar/gkaa913Edgar RC. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics. 2004;5:113. doi: 10.1186/1471-2105-5-113Lang BF, Beck N, Prince S, Sarrasin M, Rioux P, Burger G. Mitochondrial genome annotation with MFannot: a critical analysis of gene identification and gene model prediction. Front Plant Sci. 2023;14:1222186. doi: 10.3389/fpls.2023.1222186Lang BF, Beck N, Prince S, et al. Mitochondrial genome annotation with MFannot: a critical analysis of gene identification and gene model prediction. Front Plant Sci. 2023;14:1222186. doi: 10.3389/fpls.2023.1222186Baradaran R, Berrisford JM, Minhas GS, Sazanov LA. Crystal structure of the entire respiratory complex I. Nature. 2013;494(7438):443-448. doi: 10.1038/nature11871Grivennikova VG, Gladyshev GV, Zharova TV, Borisov VB. Proton-translocating NADH-ubiquinone oxidoreductase: interaction with artificial electron aAcceptors, inhibitors, and potential medicines. Int J Mol Sci. 2024;25(24). doi: 10.3390/ijms252413421Grivennikova VG, Gladyshev GV, Zharova TV, Borisov VB. Proton-Translocating NADH-Ubiquinone Oxidoreductase: Interaction with Artificial Electron Acceptors, Inhibitors, and Potential Medicines. Int J Mol Sci. 2024;25(24). doi: 10.3390/ijms252413421Brandt U. Energy converting NADH:quinone oxidoreductase (complex I). Annu Rev Biochem. 2006;75:69-92. doi: 10.1146/annurev.biochem.75.103004.142539Moparthi VK, Hägerhäll C. The evolution of respiratory chain complex I from a smaller last common ancestor consisting of 11 protein subunits. J Mol Evol. 2011;72(5-6):484-497. doi: 10.1007/s00239-011-9447-2Friedrich T, Scheide D. The respiratory complex I of bacteria, archaea and eukarya and its module common with membrane-bound multisubunit hydrogenases. FEBS Lett. 2000;479(1-2):1-5. doi: 10.1016/s0014-5793(00)01867-6Marreiros BC, Batista AP, Duarte AM, Pereira MM. A missing link between complex I and group 4 membrane-bound [NiFe] hydrogenases. Biochim Biophys Acta. 2013;1827(2):198-209. doi: 10.1016/j.bbabio.2012.09.012Novakovsky GE, Dibrova DV, Mulkidjanian AY. Phylogenomic analysis of type 1 NADH:quinone oxidoreductase. Biochemistry (Mosc). 2016;81(7):770-784. doi: 10.1134/S0006297916070142Novakovsky GE, Dibrova DV, Mulkidjanian AY. Phylogenomic Analysis of Type 1 NADH:Quinone Oxidoreductase. Biochemistry (Moscow). 2016;81(7):770-784. doi: 10.1134/S0006297916070142Schut GJ, Boyd ES, Peters JW, Adams MW. The modular respiratory complexes involved in hydrogen and sulfur metabolism by heterotrophic hyperthermophilic archaea and their evolutionary implications. FEMS Microbiol Rev. 2013;37(2):182-203. doi: 10.1111/j.1574-6976.2012.00346.xLiang Y, Plourde A, Bueler SA, et al. Structure of mycobacterial respiratory complex I. Proc Natl Acad Sci U S A. 2023;120(13):e2214949120. doi: 10.1073/pnas.2214949120Liang Y, Plourde A, Bueler SA, et al. Structure of mycobacterial respiratory complex I. Proc Natl Acad Sci USA. 2023;120(13):e2214949120. doi: 10.1073/pnas.2214949120Vignais PM, Billoud B, Meyer J. Classification and phylogeny of hydrogenases. FEMS Microbiol Rev. 2001;25(4):455-501. doi: 10.1111/j.1574-6976.2001.tb00587.xSazanov LA, Hinchliffe P. Structure of the hydrophilic domain of respiratory complex I from Thermus Thermophilus. Science. 2006;311(5766):1430-1436. doi: 10.1126/science.1123809Sazanov LA, Hinchliffe P. Structure of the hydrophilic domain of respiratory complex I from Thermus thermophilus. Science. 2006;311(5766):1430-1436. doi: 10.1126/science.1123809Reyes-Prieto A, Barquera B, Juárez O. Origin and evolution of the sodium-pumping NADH:ubiquinone oxidoreductase. PLoS One. 2014;9(5):e96696. doi: 10.1371/journal.pone.0096696Reyes-Prieto A, Barquera B, Juarez O. Origin and Evolution of the Sodium-Pumping NADH:Ubiquinone Oxidoreductase. PLoS One. 2014;9(5):e96696. doi: 10.1371/journal.pone.0096696Steuber J, Vohl G, Muras V, et al. The structure of Na+-translocating of NADH:ubiquinone oxidoreductase of Vibrio cholerae: implications on coupling between electron transfer and Na+ transport. Biol Chem. 2015;396(9-10):1015-1030. doi: 10.1515/hsz-2015-0128Mathiesen C, Hägerhäll C. The ‘antiporter module’ of respiratory chain complex I includes the MrpC/NuoK subunit - a revision of the modular evolution scheme. FEBS Lett. 2003;549(1-3):7-13. doi: 10.1016/s0014-5793(03)00767-1Mathiesen C, Hägerhäll C. The ‘antiporter module’ of respiratory chain complex I includes the MrpC/NuoK subunit — a revision of the modular evolution scheme. FEBS Lett. 2003;549(1-3):7-13. doi: 10.1016/s0014-5793(03)00767-1Mathiesen C, Hägerhäll C. Transmembrane topology of the NuoL, M and N subunits of NADH:quinone oxidoreductase and their homologues among membrane-bound hydrogenases and bona fide antiporters. Biochim Biophys Acta. 2002;1556(2-3):121-132. doi: 10.1016/S0005-2728(02)00343-2Mayer S, Steffen W, Steuber J, Götz F. The staphylococcus aureus nuoL-like protein MpsA contributes to the generation of membrane potential. J Bacteriol. 2015;197(5):794-806. doi: 10.1128/JB.02127-14Mayer S, Steffen W, Steuber J, Gotz F. The Staphylococcus aureus NuoL-like protein MpsA contributes to the generation of membrane potential. J Bacteriol. 2015;197(5):794-806. doi: 10.1128/JB.02127-14Fan SH, Ebner P, Reichert S, et al. MpsAB is important for Staphylococcus aureus virulence and growth at atmospheric CO2 levels. Nat Commun. 2019;10(1):3627. doi: 10.1038/s41467-019-11547-5Douglas EJA, Duggan S, Brignoli T, Massey RC. The MpsB protein contributes to both the toxicity and immune evasion capacity of Staphylococcus aureus. Microbiology (Reading). 2021;167(10). doi: 10.1099/mic.0.001096Klimchuk OI, Konovalov KA, Perekhvatov VV, Skulachev KV, Dibrova DV, Mulkidjanian AY. COGNAT: a web server for comparative analysis of genomic neighborhoods. Biol Direct. 2017;12(1):26. doi: 10.1186/s13062-017-0196-zKlimchuk OI, Konovalov KA, Perekhvatov VV, et al. COGNAT: a web server for comparative analysis of genomic neighborhoods. Biol Direct. 2017;12(1):26. doi: 10.1186/s13062-017-0196-zBuckel W, Ermler U, Vonck J, Fritz G, Steuber J. The RNF/NQR redox pumps: a versatile system for energy transduction in bacteria and archaea. Appl Microbiol Biotechnol. 2025;109(1):148. doi: 10.1007/s00253-025-13531-0Buckel W, Ermler U, Vonck J, et al. The RNF/NQR redox pumps: a versatile system for energy transduction in bacteria and archaea. Appl Microbiol Biotechnol. 2025;109(1):148. doi: 10.1007/s00253-025-13531-0Reyes-Prieto A, Barquera B, Juárez O. Origin and evolution of the sodium-pumping NADH:ubiquinone oxidoreductase. PLoS One. 2014;9(5):e96696. doi: 10.1371/journal.pone.0096696Reyes-Prieto A, Barquera B, Juarez O. Origin and Evolution of the Sodium-Pumping NADH:Ubiquinone Oxidoreductase. PLoS One. 2014;9(5):e96696. doi: 10.1371/journal.pone.0096696