[{"project":[{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program"}],"article_number":"e1008079","title":"An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape","external_id":{"isi":["000466866000029"]},"article_processing_charge":"No","author":[{"first_name":"Victoria","id":"3184041C-F248-11E8-B48F-1D18A9856A87","last_name":"Pokusaeva","full_name":"Pokusaeva, Victoria","orcid":"0000-0001-7660-444X"},{"full_name":"Usmanova, Dinara R.","last_name":"Usmanova","first_name":"Dinara R."},{"first_name":"Ekaterina V.","last_name":"Putintseva","full_name":"Putintseva, Ekaterina V."},{"first_name":"Lorena","last_name":"Espinar","full_name":"Espinar, Lorena"},{"full_name":"Sarkisyan, Karen","orcid":"0000-0002-5375-6341","last_name":"Sarkisyan","first_name":"Karen","id":"39A7BF80-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alexander S.","last_name":"Mishin","full_name":"Mishin, Alexander S."},{"last_name":"Bogatyreva","full_name":"Bogatyreva, Natalya S.","first_name":"Natalya S."},{"last_name":"Ivankov","full_name":"Ivankov, Dmitry","first_name":"Dmitry","id":"49FF1036-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Akopyan","full_name":"Akopyan, Arseniy","orcid":"0000-0002-2548-617X","first_name":"Arseniy","id":"430D2C90-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Avvakumov","full_name":"Avvakumov, Sergey","id":"3827DAC8-F248-11E8-B48F-1D18A9856A87","first_name":"Sergey"},{"first_name":"Inna S.","last_name":"Povolotskaya","full_name":"Povolotskaya, Inna S."},{"first_name":"Guillaume J.","full_name":"Filion, Guillaume J.","last_name":"Filion"},{"last_name":"Carey","full_name":"Carey, Lucas B.","first_name":"Lucas B."},{"orcid":"0000-0001-8243-4694","full_name":"Kondrashov, Fyodor","last_name":"Kondrashov","first_name":"Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"mla":"Pokusaeva, Victoria, et al. “An Experimental Assay of the Interactions of Amino Acids from Orthologous Sequences Shaping a Complex Fitness Landscape.” PLoS Genetics, vol. 15, no. 4, e1008079, Public Library of Science, 2019, doi:10.1371/journal.pgen.1008079.","ieee":"V. Pokusaeva et al., “An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape,” PLoS Genetics, vol. 15, no. 4. Public Library of Science, 2019.","short":"V. Pokusaeva, D.R. Usmanova, E.V. Putintseva, L. Espinar, K. Sarkisyan, A.S. Mishin, N.S. Bogatyreva, D. Ivankov, A. Akopyan, S. Avvakumov, I.S. Povolotskaya, G.J. Filion, L.B. Carey, F. Kondrashov, PLoS Genetics 15 (2019).","apa":"Pokusaeva, V., Usmanova, D. R., Putintseva, E. V., Espinar, L., Sarkisyan, K., Mishin, A. S., … Kondrashov, F. (2019). An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1008079","ama":"Pokusaeva V, Usmanova DR, Putintseva EV, et al. An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape. PLoS Genetics. 2019;15(4). doi:10.1371/journal.pgen.1008079","chicago":"Pokusaeva, Victoria, Dinara R. Usmanova, Ekaterina V. Putintseva, Lorena Espinar, Karen Sarkisyan, Alexander S. Mishin, Natalya S. Bogatyreva, et al. “An Experimental Assay of the Interactions of Amino Acids from Orthologous Sequences Shaping a Complex Fitness Landscape.” PLoS Genetics. Public Library of Science, 2019. https://doi.org/10.1371/journal.pgen.1008079.","ista":"Pokusaeva V, Usmanova DR, Putintseva EV, Espinar L, Sarkisyan K, Mishin AS, Bogatyreva NS, Ivankov D, Akopyan A, Avvakumov S, Povolotskaya IS, Filion GJ, Carey LB, Kondrashov F. 2019. An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape. PLoS Genetics. 15(4), e1008079."},"oa":1,"publisher":"Public Library of Science","quality_controlled":"1","date_created":"2019-05-13T07:58:38Z","doi":"10.1371/journal.pgen.1008079","date_published":"2019-04-10T00:00:00Z","publication":"PLoS Genetics","day":"10","year":"2019","isi":1,"has_accepted_license":"1","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","_id":"6419","department":[{"_id":"FyKo"}],"file_date_updated":"2020-07-14T12:47:30Z","ddc":["570"],"date_updated":"2023-08-25T10:30:37Z","intvolume":" 15","month":"04","scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Characterizing the fitness landscape, a representation of fitness for a large set of genotypes, is key to understanding how genetic information is interpreted to create functional organisms. Here we determined the evolutionarily-relevant segment of the fitness landscape of His3, a gene coding for an enzyme in the histidine synthesis pathway, focusing on combinations of amino acid states found at orthologous sites of extant species. Just 15% of amino acids found in yeast His3 orthologues were always neutral while the impact on fitness of the remaining 85% depended on the genetic background. Furthermore, at 67% of sites, amino acid replacements were under sign epistasis, having both strongly positive and negative effect in different genetic backgrounds. 46% of sites were under reciprocal sign epistasis. The fitness impact of amino acid replacements was influenced by only a few genetic backgrounds but involved interaction of multiple sites, shaping a rugged fitness landscape in which many of the shortest paths between highly fit genotypes are inaccessible."}],"license":"https://creativecommons.org/licenses/by/4.0/","ec_funded":1,"volume":15,"related_material":{"record":[{"status":"public","id":"9789","relation":"research_data"},{"relation":"research_data","id":"9790","status":"public"},{"relation":"research_data","id":"9797","status":"public"}]},"issue":"4","language":[{"iso":"eng"}],"file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_id":"6445","checksum":"cf3889c8a8a16053dacf9c3776cbe217","creator":"dernst","file_size":3726017,"date_updated":"2020-07-14T12:47:30Z","file_name":"2019_PLOSGenetics_Pokusaeva.pdf","date_created":"2019-05-14T08:26:08Z"}],"publication_status":"published","publication_identifier":{"eissn":["15537404"]}},{"type":"research_data_reference","status":"public","_id":"9790","article_processing_charge":"No","author":[{"orcid":"0000-0001-7660-444X","full_name":"Pokusaeva, Victoria","last_name":"Pokusaeva","first_name":"Victoria","id":"3184041C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Usmanova","full_name":"Usmanova, Dinara R.","first_name":"Dinara R."},{"first_name":"Ekaterina V.","last_name":"Putintseva","full_name":"Putintseva, Ekaterina V."},{"last_name":"Espinar","full_name":"Espinar, Lorena","first_name":"Lorena"},{"id":"39A7BF80-F248-11E8-B48F-1D18A9856A87","first_name":"Karen","last_name":"Sarkisyan","orcid":"0000-0002-5375-6341","full_name":"Sarkisyan, Karen"},{"last_name":"Mishin","full_name":"Mishin, Alexander S.","first_name":"Alexander S."},{"first_name":"Natalya S.","full_name":"Bogatyreva, Natalya S.","last_name":"Bogatyreva"},{"last_name":"Ivankov","full_name":"Ivankov, Dmitry","id":"49FF1036-F248-11E8-B48F-1D18A9856A87","first_name":"Dmitry"},{"first_name":"Arseniy","id":"430D2C90-F248-11E8-B48F-1D18A9856A87","last_name":"Akopyan","full_name":"Akopyan, Arseniy","orcid":"0000-0002-2548-617X"},{"first_name":"Sergey","id":"3827DAC8-F248-11E8-B48F-1D18A9856A87","full_name":"Avvakumov, Sergey","last_name":"Avvakumov"},{"full_name":"Povolotskaya, Inna S.","last_name":"Povolotskaya","first_name":"Inna S."},{"last_name":"Filion","full_name":"Filion, Guillaume J.","first_name":"Guillaume J."},{"last_name":"Carey","full_name":"Carey, Lucas B.","first_name":"Lucas B."},{"id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","first_name":"Fyodor","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694","last_name":"Kondrashov"}],"department":[{"_id":"FyKo"}],"title":"A statistical summary of segment libraries and sequencing results","citation":{"ista":"Pokusaeva V, Usmanova DR, Putintseva EV, Espinar L, Sarkisyan K, Mishin AS, Bogatyreva NS, Ivankov D, Akopyan A, Avvakumov S, Povolotskaya IS, Filion GJ, Carey LB, Kondrashov F. 2019. A statistical summary of segment libraries and sequencing results, Public Library of Science, 10.1371/journal.pgen.1008079.s011.","chicago":"Pokusaeva, Victoria, Dinara R. Usmanova, Ekaterina V. Putintseva, Lorena Espinar, Karen Sarkisyan, Alexander S. Mishin, Natalya S. Bogatyreva, et al. “A Statistical Summary of Segment Libraries and Sequencing Results.” Public Library of Science, 2019. https://doi.org/10.1371/journal.pgen.1008079.s011.","apa":"Pokusaeva, V., Usmanova, D. R., Putintseva, E. V., Espinar, L., Sarkisyan, K., Mishin, A. S., … Kondrashov, F. (2019). A statistical summary of segment libraries and sequencing results. Public Library of Science. https://doi.org/10.1371/journal.pgen.1008079.s011","ama":"Pokusaeva V, Usmanova DR, Putintseva EV, et al. A statistical summary of segment libraries and sequencing results. 2019. doi:10.1371/journal.pgen.1008079.s011","short":"V. Pokusaeva, D.R. Usmanova, E.V. Putintseva, L. Espinar, K. Sarkisyan, A.S. Mishin, N.S. Bogatyreva, D. Ivankov, A. Akopyan, S. Avvakumov, I.S. Povolotskaya, G.J. Filion, L.B. Carey, F. Kondrashov, (2019).","ieee":"V. Pokusaeva et al., “A statistical summary of segment libraries and sequencing results.” Public Library of Science, 2019.","mla":"Pokusaeva, Victoria, et al. A Statistical Summary of Segment Libraries and Sequencing Results. Public Library of Science, 2019, doi:10.1371/journal.pgen.1008079.s011."},"date_updated":"2023-08-25T10:30:36Z","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","publisher":"Public Library of Science","month":"04","oa_version":"Published Version","date_created":"2021-08-06T08:50:15Z","date_published":"2019-04-10T00:00:00Z","doi":"10.1371/journal.pgen.1008079.s011","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"6419"}]},"year":"2019","day":"10"},{"_id":"9797","status":"public","type":"research_data_reference","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","date_updated":"2023-08-25T10:30:36Z","citation":{"chicago":"Pokusaeva, Victoria, Dinara R. Usmanova, Ekaterina V. Putintseva, Lorena Espinar, Karen Sarkisyan, Alexander S. Mishin, Natalya S. Bogatyreva, et al. “A Statistical Summary of Segment Libraries and Sequencing Results.” Public Library of Science, 2019. https://doi.org/10.1371/journal.pgen.1008079.s011.","ista":"Pokusaeva V, Usmanova DR, Putintseva EV, Espinar L, Sarkisyan K, Mishin AS, Bogatyreva NS, Ivankov D, Akopyan A, Povolotskaya IS, Filion GJ, Carey LB, Kondrashov F. 2019. A statistical summary of segment libraries and sequencing results, Public Library of Science, 10.1371/journal.pgen.1008079.s011.","mla":"Pokusaeva, Victoria, et al. A Statistical Summary of Segment Libraries and Sequencing Results. Public Library of Science, 2019, doi:10.1371/journal.pgen.1008079.s011.","ama":"Pokusaeva V, Usmanova DR, Putintseva EV, et al. A statistical summary of segment libraries and sequencing results. 2019. doi:10.1371/journal.pgen.1008079.s011","apa":"Pokusaeva, V., Usmanova, D. R., Putintseva, E. V., Espinar, L., Sarkisyan, K., Mishin, A. S., … Kondrashov, F. (2019). A statistical summary of segment libraries and sequencing results. Public Library of Science. https://doi.org/10.1371/journal.pgen.1008079.s011","ieee":"V. Pokusaeva et al., “A statistical summary of segment libraries and sequencing results.” Public Library of Science, 2019.","short":"V. Pokusaeva, D.R. Usmanova, E.V. Putintseva, L. Espinar, K. Sarkisyan, A.S. Mishin, N.S. Bogatyreva, D. Ivankov, A. Akopyan, I.S. Povolotskaya, G.J. Filion, L.B. Carey, F. Kondrashov, (2019)."},"department":[{"_id":"FyKo"}],"title":"A statistical summary of segment libraries and sequencing results","article_processing_charge":"No","author":[{"id":"3184041C-F248-11E8-B48F-1D18A9856A87","first_name":"Victoria","last_name":"Pokusaeva","orcid":"0000-0001-7660-444X","full_name":"Pokusaeva, Victoria"},{"first_name":"Dinara R.","full_name":"Usmanova, Dinara R.","last_name":"Usmanova"},{"first_name":"Ekaterina V.","last_name":"Putintseva","full_name":"Putintseva, Ekaterina V."},{"first_name":"Lorena","full_name":"Espinar, Lorena","last_name":"Espinar"},{"last_name":"Sarkisyan","full_name":"Sarkisyan, Karen","orcid":"0000-0002-5375-6341","first_name":"Karen","id":"39A7BF80-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Mishin","full_name":"Mishin, Alexander S.","first_name":"Alexander S."},{"first_name":"Natalya S.","full_name":"Bogatyreva, Natalya S.","last_name":"Bogatyreva"},{"first_name":"Dmitry","id":"49FF1036-F248-11E8-B48F-1D18A9856A87","full_name":"Ivankov, Dmitry","last_name":"Ivankov"},{"first_name":"Arseniy","id":"430D2C90-F248-11E8-B48F-1D18A9856A87","full_name":"Akopyan, Arseniy","orcid":"0000-0002-2548-617X","last_name":"Akopyan"},{"first_name":"Inna S.","full_name":"Povolotskaya, Inna S.","last_name":"Povolotskaya"},{"first_name":"Guillaume J.","last_name":"Filion","full_name":"Filion, Guillaume J."},{"full_name":"Carey, Lucas B.","last_name":"Carey","first_name":"Lucas B."},{"last_name":"Kondrashov","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","first_name":"Fyodor"}],"oa_version":"Published Version","month":"04","publisher":"Public Library of Science","day":"10","year":"2019","date_created":"2021-08-06T11:08:20Z","related_material":{"record":[{"status":"public","id":"6419","relation":"used_in_publication"}]},"doi":"10.1371/journal.pgen.1008079.s011","date_published":"2019-04-10T00:00:00Z"},{"author":[{"id":"3184041C-F248-11E8-B48F-1D18A9856A87","first_name":"Victoria","orcid":"0000-0001-7660-444X","full_name":"Pokusaeva, Victoria","last_name":"Pokusaeva"},{"full_name":"Usmanova, Dinara R.","last_name":"Usmanova","first_name":"Dinara R."},{"first_name":"Ekaterina V.","last_name":"Putintseva","full_name":"Putintseva, Ekaterina V."},{"full_name":"Espinar, Lorena","last_name":"Espinar","first_name":"Lorena"},{"last_name":"Sarkisyan","orcid":"0000-0002-5375-6341","full_name":"Sarkisyan, Karen","id":"39A7BF80-F248-11E8-B48F-1D18A9856A87","first_name":"Karen"},{"first_name":"Alexander S.","full_name":"Mishin, Alexander S.","last_name":"Mishin"},{"first_name":"Natalya S.","full_name":"Bogatyreva, Natalya S.","last_name":"Bogatyreva"},{"first_name":"Dmitry","id":"49FF1036-F248-11E8-B48F-1D18A9856A87","full_name":"Ivankov, Dmitry","last_name":"Ivankov"},{"last_name":"Akopyan","full_name":"Akopyan, Arseniy","orcid":"0000-0002-2548-617X","first_name":"Arseniy","id":"430D2C90-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Avvakumov, Sergey","last_name":"Avvakumov","id":"3827DAC8-F248-11E8-B48F-1D18A9856A87","first_name":"Sergey"},{"last_name":"Povolotskaya","full_name":"Povolotskaya, Inna S.","first_name":"Inna S."},{"first_name":"Guillaume J.","last_name":"Filion","full_name":"Filion, Guillaume J."},{"first_name":"Lucas B.","last_name":"Carey","full_name":"Carey, Lucas B."},{"first_name":"Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","last_name":"Kondrashov","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694"}],"article_processing_charge":"No","title":"Multiple alignment of His3 orthologues","department":[{"_id":"FyKo"}],"date_updated":"2023-08-25T10:30:36Z","citation":{"mla":"Pokusaeva, Victoria, et al. Multiple Alignment of His3 Orthologues. Public Library of Science, 2019, doi:10.1371/journal.pgen.1008079.s010.","ieee":"V. Pokusaeva et al., “Multiple alignment of His3 orthologues.” Public Library of Science, 2019.","short":"V. Pokusaeva, D.R. Usmanova, E.V. Putintseva, L. Espinar, K. Sarkisyan, A.S. Mishin, N.S. Bogatyreva, D. Ivankov, A. Akopyan, S. Avvakumov, I.S. Povolotskaya, G.J. Filion, L.B. Carey, F. Kondrashov, (2019).","apa":"Pokusaeva, V., Usmanova, D. R., Putintseva, E. V., Espinar, L., Sarkisyan, K., Mishin, A. S., … Kondrashov, F. (2019). Multiple alignment of His3 orthologues. Public Library of Science. https://doi.org/10.1371/journal.pgen.1008079.s010","ama":"Pokusaeva V, Usmanova DR, Putintseva EV, et al. Multiple alignment of His3 orthologues. 2019. doi:10.1371/journal.pgen.1008079.s010","chicago":"Pokusaeva, Victoria, Dinara R. Usmanova, Ekaterina V. Putintseva, Lorena Espinar, Karen Sarkisyan, Alexander S. Mishin, Natalya S. Bogatyreva, et al. “Multiple Alignment of His3 Orthologues.” Public Library of Science, 2019. https://doi.org/10.1371/journal.pgen.1008079.s010.","ista":"Pokusaeva V, Usmanova DR, Putintseva EV, Espinar L, Sarkisyan K, Mishin AS, Bogatyreva NS, Ivankov D, Akopyan A, Avvakumov S, Povolotskaya IS, Filion GJ, Carey LB, Kondrashov F. 2019. Multiple alignment of His3 orthologues, Public Library of Science, 10.1371/journal.pgen.1008079.s010."},"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","type":"research_data_reference","status":"public","_id":"9789","date_published":"2019-04-10T00:00:00Z","doi":"10.1371/journal.pgen.1008079.s010","related_material":{"record":[{"relation":"used_in_publication","id":"6419","status":"public"}]},"date_created":"2021-08-06T08:38:50Z","year":"2019","day":"10","publisher":"Public Library of Science","month":"04","oa_version":"Published Version"},{"external_id":{"isi":["000452866000068"]},"article_processing_charge":"No","author":[{"full_name":"Kotlobay, Alexey A.","last_name":"Kotlobay","first_name":"Alexey A."},{"last_name":"Sarkisyan","orcid":"0000-0002-5375-6341","full_name":"Sarkisyan, Karen","id":"39A7BF80-F248-11E8-B48F-1D18A9856A87","first_name":"Karen"},{"full_name":"Mokrushina, Yuliana A.","last_name":"Mokrushina","first_name":"Yuliana A."},{"first_name":"Marina","full_name":"Marcet-Houben, Marina","last_name":"Marcet-Houben"},{"first_name":"Ekaterina O.","last_name":"Serebrovskaya","full_name":"Serebrovskaya, Ekaterina O."},{"first_name":"Nadezhda M.","last_name":"Markina","full_name":"Markina, Nadezhda M."},{"orcid":"0000-0001-9139-5383","full_name":"Gonzalez Somermeyer, Louisa","last_name":"Gonzalez Somermeyer","id":"4720D23C-F248-11E8-B48F-1D18A9856A87","first_name":"Louisa"},{"first_name":"Andrey Y.","full_name":"Gorokhovatsky, Andrey Y.","last_name":"Gorokhovatsky"},{"full_name":"Vvedensky, Andrey","last_name":"Vvedensky","first_name":"Andrey"},{"first_name":"Konstantin V.","last_name":"Purtov","full_name":"Purtov, Konstantin V."},{"first_name":"Valentin N.","full_name":"Petushkov, Valentin N.","last_name":"Petushkov"},{"last_name":"Rodionova","full_name":"Rodionova, Natalja S.","first_name":"Natalja S."},{"first_name":"Tatiana V.","full_name":"Chepurnyh, Tatiana V.","last_name":"Chepurnyh"},{"first_name":"Liliia","last_name":"Fakhranurova","full_name":"Fakhranurova, Liliia"},{"first_name":"Elena B.","full_name":"Guglya, Elena B.","last_name":"Guglya"},{"first_name":"Rustam","last_name":"Ziganshin","full_name":"Ziganshin, Rustam"},{"first_name":"Aleksandra S.","full_name":"Tsarkova, Aleksandra S.","last_name":"Tsarkova"},{"last_name":"Kaskova","full_name":"Kaskova, Zinaida M.","first_name":"Zinaida M."},{"last_name":"Shender","full_name":"Shender, Victoria","first_name":"Victoria"},{"full_name":"Abakumov, Maxim","last_name":"Abakumov","first_name":"Maxim"},{"first_name":"Tatiana O.","last_name":"Abakumova","full_name":"Abakumova, Tatiana O."},{"full_name":"Povolotskaya, Inna S.","last_name":"Povolotskaya","first_name":"Inna S."},{"first_name":"Fedor M.","full_name":"Eroshkin, Fedor M.","last_name":"Eroshkin"},{"first_name":"Andrey G.","full_name":"Zaraisky, Andrey G.","last_name":"Zaraisky"},{"first_name":"Alexander S.","last_name":"Mishin","full_name":"Mishin, Alexander S."},{"first_name":"Sergey V.","full_name":"Dolgov, Sergey V.","last_name":"Dolgov"},{"first_name":"Tatiana Y.","last_name":"Mitiouchkina","full_name":"Mitiouchkina, Tatiana Y."},{"first_name":"Eugene P.","full_name":"Kopantzev, Eugene P.","last_name":"Kopantzev"},{"first_name":"Hans E.","full_name":"Waldenmaier, Hans E.","last_name":"Waldenmaier"},{"last_name":"Oliveira","full_name":"Oliveira, Anderson G.","first_name":"Anderson G."},{"last_name":"Oba","full_name":"Oba, Yuichi","first_name":"Yuichi"},{"first_name":"Ekaterina","full_name":"Barsova, Ekaterina","last_name":"Barsova"},{"last_name":"Bogdanova","full_name":"Bogdanova, Ekaterina A.","first_name":"Ekaterina A."},{"full_name":"Gabaldón, Toni","last_name":"Gabaldón","first_name":"Toni"},{"full_name":"Stevani, Cassius V.","last_name":"Stevani","first_name":"Cassius V."},{"first_name":"Sergey","last_name":"Lukyanov","full_name":"Lukyanov, Sergey"},{"first_name":"Ivan V.","full_name":"Smirnov, Ivan V.","last_name":"Smirnov"},{"first_name":"Josef I.","full_name":"Gitelson, Josef I.","last_name":"Gitelson"},{"last_name":"Kondrashov","orcid":"0000-0001-8243-4694","full_name":"Kondrashov, Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","first_name":"Fyodor"},{"full_name":"Yampolsky, Ilia V.","last_name":"Yampolsky","first_name":"Ilia V."}],"title":"Genetically encodable bioluminescent system from fungi","citation":{"ista":"Kotlobay AA, Sarkisyan K, Mokrushina YA, Marcet-Houben M, Serebrovskaya EO, Markina NM, Gonzalez Somermeyer L, Gorokhovatsky AY, Vvedensky A, Purtov KV, Petushkov VN, Rodionova NS, Chepurnyh TV, Fakhranurova L, Guglya EB, Ziganshin R, Tsarkova AS, Kaskova ZM, Shender V, Abakumov M, Abakumova TO, Povolotskaya IS, Eroshkin FM, Zaraisky AG, Mishin AS, Dolgov SV, Mitiouchkina TY, Kopantzev EP, Waldenmaier HE, Oliveira AG, Oba Y, Barsova E, Bogdanova EA, Gabaldón T, Stevani CV, Lukyanov S, Smirnov IV, Gitelson JI, Kondrashov F, Yampolsky IV. 2018. Genetically encodable bioluminescent system from fungi. Proceedings of the National Academy of Sciences of the United States of America. 115(50), 12728–12732.","chicago":"Kotlobay, Alexey A., Karen Sarkisyan, Yuliana A. Mokrushina, Marina Marcet-Houben, Ekaterina O. Serebrovskaya, Nadezhda M. Markina, Louisa Gonzalez Somermeyer, et al. “Genetically Encodable Bioluminescent System from Fungi.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2018. https://doi.org/10.1073/pnas.1803615115.","short":"A.A. Kotlobay, K. Sarkisyan, Y.A. Mokrushina, M. Marcet-Houben, E.O. Serebrovskaya, N.M. Markina, L. Gonzalez Somermeyer, A.Y. Gorokhovatsky, A. Vvedensky, K.V. Purtov, V.N. Petushkov, N.S. Rodionova, T.V. Chepurnyh, L. Fakhranurova, E.B. Guglya, R. Ziganshin, A.S. Tsarkova, Z.M. Kaskova, V. Shender, M. Abakumov, T.O. Abakumova, I.S. Povolotskaya, F.M. Eroshkin, A.G. Zaraisky, A.S. Mishin, S.V. Dolgov, T.Y. Mitiouchkina, E.P. Kopantzev, H.E. Waldenmaier, A.G. Oliveira, Y. Oba, E. Barsova, E.A. Bogdanova, T. Gabaldón, C.V. Stevani, S. Lukyanov, I.V. Smirnov, J.I. Gitelson, F. Kondrashov, I.V. Yampolsky, Proceedings of the National Academy of Sciences of the United States of America 115 (2018) 12728–12732.","ieee":"A. A. Kotlobay et al., “Genetically encodable bioluminescent system from fungi,” Proceedings of the National Academy of Sciences of the United States of America, vol. 115, no. 50. National Academy of Sciences, pp. 12728–12732, 2018.","ama":"Kotlobay AA, Sarkisyan K, Mokrushina YA, et al. Genetically encodable bioluminescent system from fungi. Proceedings of the National Academy of Sciences of the United States of America. 2018;115(50):12728-12732. doi:10.1073/pnas.1803615115","apa":"Kotlobay, A. A., Sarkisyan, K., Mokrushina, Y. A., Marcet-Houben, M., Serebrovskaya, E. O., Markina, N. M., … Yampolsky, I. V. (2018). Genetically encodable bioluminescent system from fungi. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.1803615115","mla":"Kotlobay, Alexey A., et al. “Genetically Encodable Bioluminescent System from Fungi.” Proceedings of the National Academy of Sciences of the United States of America, vol. 115, no. 50, National Academy of Sciences, 2018, pp. 12728–32, doi:10.1073/pnas.1803615115."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa":1,"quality_controlled":"1","publisher":"National Academy of Sciences","page":"12728-12732","date_created":"2018-12-23T22:59:18Z","doi":"10.1073/pnas.1803615115","date_published":"2018-12-11T00:00:00Z","year":"2018","isi":1,"has_accepted_license":"1","publication":"Proceedings of the National Academy of Sciences of the United States of America","day":"11","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"type":"journal_article","status":"public","_id":"5780","department":[{"_id":"FyKo"}],"file_date_updated":"2020-07-14T12:47:11Z","date_updated":"2023-09-11T14:04:05Z","ddc":["580"],"scopus_import":"1","intvolume":" 115","month":"12","abstract":[{"text":"Bioluminescence is found across the entire tree of life, conferring a spectacular set of visually oriented functions from attracting mates to scaring off predators. Half a dozen different luciferins, molecules that emit light when enzymatically oxidized, are known. However, just one biochemical pathway for luciferin biosynthesis has been described in full, which is found only in bacteria. Here, we report identification of the fungal luciferase and three other key enzymes that together form the biosynthetic cycle of the fungal luciferin from caffeic acid, a simple and widespread metabolite. Introduction of the identified genes into the genome of the yeast Pichia pastoris along with caffeic acid biosynthesis genes resulted in a strain that is autoluminescent in standard media. We analyzed evolution of the enzymes of the luciferin biosynthesis cycle and found that fungal bioluminescence emerged through a series of events that included two independent gene duplications. The retention of the duplicated enzymes of the luciferin pathway in nonluminescent fungi shows that the gene duplication was followed by functional sequence divergence of enzymes of at least one gene in the biosynthetic pathway and suggests that the evolution of fungal bioluminescence proceeded through several closely related stepping stone nonluminescent biochemical reactions with adaptive roles. The availability of a complete eukaryotic luciferin biosynthesis pathway provides several applications in biomedicine and bioengineering.","lang":"eng"}],"oa_version":"Published Version","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","issue":"50","volume":115,"publication_status":"published","publication_identifier":{"issn":["00278424"]},"language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"46b2c12185eb2ddb598f4c7b4bd267bf","file_id":"5926","date_updated":"2020-07-14T12:47:11Z","file_size":1271988,"creator":"dernst","date_created":"2019-02-05T15:21:40Z","file_name":"2018_PNAS_Kotlobay.pdf"}]},{"page":"397 - 401","date_created":"2018-12-11T11:48:50Z","date_published":"2016-05-11T00:00:00Z","doi":"10.1038/nature17995","volume":533,"publication_status":"published","year":"2016","publication":"Nature","day":"11","publisher":"Nature Publishing Group","quality_controlled":0,"intvolume":" 533","month":"05","abstract":[{"lang":"eng","text":"Fitness landscapes depict how genotypes manifest at the phenotypic level and form the basis of our understanding of many areas of biology, yet their properties remain elusive. Previous studies have analysed specific genes, often using their function as a proxy for fitness, experimentally assessing the effect on function of single mutations and their combinations in a specific sequence or in different sequences. However, systematic high-throughput studies of the local fitness landscape of an entire protein have not yet been reported. Here we visualize an extensive region of the local fitness landscape of the green fluorescent protein from Aequorea Victoria (avGFP) by measuring the native function (fluorescence) of tens of thousands of derivative genotypes of avGFP. We show that the fitness landscape of avGFP is narrow, with 3/4 of the derivatives with a single mutation showing reduced fluorescence and half of the derivatives with four mutations being completely non-fluorescent. The narrowness is enhanced by epistasis, which was detected in up to 30% of genotypes with multiple mutations and mostly occurred through the cumulative effect of slightly deleterious mutations causing a threshold-like decrease in protein stability and a concomitant loss of fluorescence. A model of orthologous sequence divergence spanning hundreds of millions of years predicted the extent of epistasis in our data, indicating congruence between the fitness landscape properties at the local and global scales. The characterization of the local fitness landscape of avGFP has important implications for several fields including molecular evolution, population genetics and protein design."}],"acknowledgement":"We thank Y. Kulikova and G. Filion for discussion on statistical analysis and I. Osterman, R. Moretti and J. Meiler for technical assistance and M. Friesen for a critical reading of the manuscript. We thank H. Himmelbauer, CRG Genomic Unit and the Russian Science Foundation project (14-50-00150) for sequencing. Experiments were partially carried out using the equipment provided by the IBCH core facility (CKP IBCH). The work was supported by HHMI International Early Career Scientist Program (55007424), the EMBO Young Investigator Programme, MINECO (BFU2012-31329), Spanish Ministry of Economy and Competitiveness Centro de Excelencia Severo Ochoa 2013-2017 grant (SEV-2012-0208), Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat's AGAUR program (2014 SGR 0974), Russian Science Foundation (14-25-00129) and the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013, ERC grant agreement, 335980-EinME).","author":[{"orcid":"0000-0002-5375-6341","full_name":"Karen Sarkisyan","last_name":"Sarkisyan","first_name":"Karen","id":"39A7BF80-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bolotin, Dmitry A","last_name":"Bolotin","first_name":"Dmitry"},{"first_name":"Margarita","full_name":"Meer, Margarita V","last_name":"Meer"},{"first_name":"Dinara","last_name":"Usmanova","full_name":"Usmanova, Dinara R"},{"first_name":"Alexander","last_name":"Mishin","full_name":"Mishin, Alexander S"},{"first_name":"George","last_name":"Sharonov","full_name":"Sharonov, George V"},{"last_name":"Ivankov","full_name":"Ivankov, Dmitry N","first_name":"Dmitry"},{"first_name":"Nina","last_name":"Bozhanova","full_name":"Bozhanova, Nina G"},{"last_name":"Baranov","full_name":"Baranov, Mikhail S","first_name":"Mikhail"},{"first_name":"Onuralp","full_name":"Soylemez, Onuralp","last_name":"Soylemez"},{"first_name":"Natalya","last_name":"Bogatyreva","full_name":"Bogatyreva, Natalya S"},{"first_name":"Peter","last_name":"Vlasov","full_name":"Vlasov, Peter K"},{"full_name":"Egorov, Evgeny S","last_name":"Egorov","first_name":"Evgeny"},{"full_name":"Logacheva, Maria D","last_name":"Logacheva","first_name":"Maria"},{"full_name":"Kondrashov, Alexey S","last_name":"Kondrashov","first_name":"Alexey"},{"first_name":"Dmitriy","full_name":"Chudakov, Dmitriy M","last_name":"Chudakov"},{"first_name":"Ekaterina","full_name":"Putintseva, Ekaterina V","last_name":"Putintseva"},{"first_name":"Ilgar","last_name":"Mamedov","full_name":"Mamedov, Ilgar Z"},{"first_name":"Dan","full_name":"Tawfik, Dan S","last_name":"Tawfik"},{"full_name":"Lukyanov, Konstantin A","last_name":"Lukyanov","first_name":"Konstantin"},{"id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","first_name":"Fyodor","last_name":"Kondrashov","full_name":"Fyodor Kondrashov","orcid":"0000-0001-8243-4694"}],"publist_id":"6799","title":"Local fitness landscape of the green fluorescent protein","date_updated":"2021-01-12T08:19:42Z","citation":{"chicago":"Sarkisyan, Karen, Dmitry Bolotin, Margarita Meer, Dinara Usmanova, Alexander Mishin, George Sharonov, Dmitry Ivankov, et al. “Local Fitness Landscape of the Green Fluorescent Protein.” Nature. Nature Publishing Group, 2016. https://doi.org/10.1038/nature17995.","ista":"Sarkisyan K, Bolotin D, Meer M, Usmanova D, Mishin A, Sharonov G, Ivankov D, Bozhanova N, Baranov M, Soylemez O, Bogatyreva N, Vlasov P, Egorov E, Logacheva M, Kondrashov A, Chudakov D, Putintseva E, Mamedov I, Tawfik D, Lukyanov K, Kondrashov F. 2016. Local fitness landscape of the green fluorescent protein. Nature. 533, 397–401.","mla":"Sarkisyan, Karen, et al. “Local Fitness Landscape of the Green Fluorescent Protein.” Nature, vol. 533, Nature Publishing Group, 2016, pp. 397–401, doi:10.1038/nature17995.","ieee":"K. Sarkisyan et al., “Local fitness landscape of the green fluorescent protein,” Nature, vol. 533. Nature Publishing Group, pp. 397–401, 2016.","short":"K. Sarkisyan, D. Bolotin, M. Meer, D. Usmanova, A. Mishin, G. Sharonov, D. Ivankov, N. Bozhanova, M. Baranov, O. Soylemez, N. Bogatyreva, P. Vlasov, E. Egorov, M. Logacheva, A. Kondrashov, D. Chudakov, E. Putintseva, I. Mamedov, D. Tawfik, K. Lukyanov, F. Kondrashov, Nature 533 (2016) 397–401.","ama":"Sarkisyan K, Bolotin D, Meer M, et al. Local fitness landscape of the green fluorescent protein. Nature. 2016;533:397-401. doi:10.1038/nature17995","apa":"Sarkisyan, K., Bolotin, D., Meer, M., Usmanova, D., Mishin, A., Sharonov, G., … Kondrashov, F. (2016). Local fitness landscape of the green fluorescent protein. Nature. Nature Publishing Group. https://doi.org/10.1038/nature17995"},"extern":1,"type":"journal_article","status":"public","_id":"850"}]