[{"title":"Pulsatile basal gene expression as a fitness determinant in bacteria","abstract":[{"lang":"eng","text":"Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of nonfunctional “promoter leakiness,” merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the noncanonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g., control of costly-to-induce multidrug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multidrug resistance is crucial for effective public health measures."}],"type":"journal_article","acknowledged_ssus":[{"_id":"Bio"}],"article_number":"e2413709122","citation":{"ista":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Pulsatile basal gene expression as a fitness determinant in bacteria. Proceedings of the National Academy of Sciences. 122(15), e2413709122.","ama":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(15). doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>","ieee":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Pulsatile basal gene expression as a fitness determinant in bacteria,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15. National Academy of Sciences, 2025.","apa":"Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., &#38; Guet, C. C. (2025). Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>","mla":"Jain, Kirti, et al. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15, e2413709122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>.","chicago":"Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper Tkačik, and Calin C Guet. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>.","short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, Proceedings of the National Academy of Sciences 122 (2025)."},"oa_version":"Published Version","publisher":"National Academy of Sciences","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"project":[{"name":"Tools for automation and feedback microscopy","_id":"c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473","grant_number":"CZI01"},{"name":"Non-canonical antibiotic interactions","grant_number":"E219","_id":"bd6f94d1-d553-11ed-ba76-ae9f07250f74"},{"name":"Evolutionary analysis of gene regulation","grant_number":"I05127","_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181"}],"month":"04","article_processing_charge":"Yes (in subscription journal)","corr_author":"1","doi":"10.1073/pnas.2413709122","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"quality_controlled":"1","publication":"Proceedings of the National Academy of Sciences","department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}],"has_accepted_license":"1","issue":"15","status":"public","language":[{"iso":"eng"}],"related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/clockwork-just-for-antibiotic-resistance/","description":"News on ISTA website"}],"record":[{"id":"19294","relation":"research_data","status":"public"}]},"date_published":"2025-04-15T00:00:00Z","external_id":{"pmid":["40193613"],"isi":["001471235200001"]},"date_created":"2025-04-27T22:02:13Z","author":[{"first_name":"Kirti","last_name":"Jain","orcid":"0000-0002-3809-0449","id":"330F0278-F248-11E8-B48F-1D18A9856A87","full_name":"Jain, Kirti"},{"last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Olga","last_name":"Bochkareva","orcid":"0000-0003-1006-6639","id":"C4558D3C-6102-11E9-A62E-F418E6697425","full_name":"Bochkareva, Olga"},{"first_name":"Roderich","last_name":"Römhild","orcid":"0000-0001-9480-5261","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","full_name":"Römhild, Roderich"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","first_name":"Gašper","last_name":"Tkačik"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet"}],"date_updated":"2026-05-20T08:33:08Z","publication_status":"published","year":"2025","file_date_updated":"2025-06-24T07:27:43Z","scopus_import":"1","acknowledgement":"K.J. thanks B. Wu, I. Tomanek, K. Tomasek for detailed discussions on the manuscript, all other members from the Guet laboratory for valuable feedback, R. Chait, & Imaging and Optics Facility, Institute of Science and Technology Austria for helping with microscopy, Dr. Sudha Rao and Dr. Raja Mugasimangalam, Genotypic Technology India for allowing time off to address the revisions. K.J. acknowledges Institute of Science and Technology fellowship IC1006FELL02, R.H. was supported in part by Chan Zuckerberg Initiative and Donor Advised-Fund grant 2020-225401 (https://doi.org/10.37921/120055ratwvi), O.O.B. acknowledges Fonds Zur Förderung der Wissenschaftlichen Forschung (FWF) Grant ESP253-B, R.R. acknowledges FWF Grant 10.55776/ESP219, C.C.G. acknowledges FWF I5127-B.","day":"15","ddc":["570"],"_id":"19626","oa":1,"intvolume":"       122","isi":1,"OA_type":"hybrid","article_type":"original","volume":122,"OA_place":"publisher","file":[{"date_updated":"2025-06-24T07:27:43Z","file_id":"19888","date_created":"2025-06-24T07:27:43Z","creator":"dernst","file_name":"2025_PNAS_Jain.pdf","checksum":"115a687f40009660eb4b38b4f6559d41","file_size":2949523,"success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"APC_amount":"5949 EUR","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]}},{"project":[{"_id":"9B767A34-BA93-11EA-9121-9846C619BF3A","grant_number":"429960716","name":"Evolution of Sensorimotor Transformation Across Diptera"},{"name":"Characterizing the fitness landscape on population and global scales","call_identifier":"H2020","_id":"26580278-B435-11E9-9278-68D0E5697425","grant_number":"771209"},{"_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181","grant_number":"I05127","name":"Evolutionary analysis of gene regulation"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"publisher":"Springer Nature","month":"07","article_processing_charge":"No","abstract":[{"text":"Constitutional heterozygous pathogenic variants in the exonuclease domain of POLE and POLD1, which affect the proofreading activity of the corresponding polymerases, cause a cancer predisposition syndrome characterized by increased risk of gastrointestinal polyposis, colorectal cancer, endometrial cancer and other tumor types. The generally accepted explanation for the connection between the disruption of the proofreading activity of polymerases epsilon and delta and cancer development is through an increase in the somatic mutation rate. Here we studied an extended family with multiple members heterozygous for the pathogenic POLD1 variant c.1421T>C p.(Leu474Pro), which segregates with the polyposis and cancer phenotypes. Through the analysis of mutational patterns of patient-derived fibroblasts colonies and de novo mutations obtained by parent-offspring comparisons, we concluded that heterozygous POLD1 L474P just subtly increases the somatic and germline mutation burden. In contrast, tumors developed in individuals with a heterozygous mutation in the exonuclease domain of POLD1, including L474P, have an extremely high mutation rate (>100 mut/Mb) associated with signature SBS10d. We solved this contradiction through the observation that tumorigenesis involves somatic inactivation of the wildtype POLD1 allele. These results imply that exonuclease deficiency of polymerase delta has a recessive effect on mutation rate.","lang":"eng"}],"type":"journal_article","title":"Discovery of recessive effect of human polymerase δ proofreading deficiency through mutational analysis of POLD1-mutated normal and cancer cells","oa_version":"Published Version","page":"837-845","citation":{"ama":"Andrianova MA, Seplyarskiy VB, Terradas M, et al. Discovery of recessive effect of human polymerase δ proofreading deficiency through mutational analysis of POLD1-mutated normal and cancer cells. <i>European Journal of Human Genetics</i>. 2024;32:837-845. doi:<a href=\"https://doi.org/10.1038/s41431-024-01598-8\">10.1038/s41431-024-01598-8</a>","ieee":"M. A. Andrianova <i>et al.</i>, “Discovery of recessive effect of human polymerase δ proofreading deficiency through mutational analysis of POLD1-mutated normal and cancer cells,” <i>European Journal of Human Genetics</i>, vol. 32. Springer Nature, pp. 837–845, 2024.","apa":"Andrianova, M. A., Seplyarskiy, V. B., Terradas, M., Sánchez-Heras, A. B., Mur, P., Soto, J. L., … Valle, L. (2024). Discovery of recessive effect of human polymerase δ proofreading deficiency through mutational analysis of POLD1-mutated normal and cancer cells. <i>European Journal of Human Genetics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41431-024-01598-8\">https://doi.org/10.1038/s41431-024-01598-8</a>","mla":"Andrianova, Maria A., et al. “Discovery of Recessive Effect of Human Polymerase δ Proofreading Deficiency through Mutational Analysis of POLD1-Mutated Normal and Cancer Cells.” <i>European Journal of Human Genetics</i>, vol. 32, Springer Nature, 2024, pp. 837–45, doi:<a href=\"https://doi.org/10.1038/s41431-024-01598-8\">10.1038/s41431-024-01598-8</a>.","ista":"Andrianova MA, Seplyarskiy VB, Terradas M, Sánchez-Heras AB, Mur P, Soto JL, Aiza G, Borràs E, Kondrashov F, Kondrashov AS, Bazykin GA, Valle L. 2024. Discovery of recessive effect of human polymerase δ proofreading deficiency through mutational analysis of POLD1-mutated normal and cancer cells. European Journal of Human Genetics. 32, 837–845.","chicago":"Andrianova, Maria A., Vladimir B. Seplyarskiy, Mariona Terradas, Ana Beatriz Sánchez-Heras, Pilar Mur, José Luis Soto, Gemma Aiza, et al. “Discovery of Recessive Effect of Human Polymerase δ Proofreading Deficiency through Mutational Analysis of POLD1-Mutated Normal and Cancer Cells.” <i>European Journal of Human Genetics</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41431-024-01598-8\">https://doi.org/10.1038/s41431-024-01598-8</a>.","short":"M.A. Andrianova, V.B. Seplyarskiy, M. Terradas, A.B. Sánchez-Heras, P. Mur, J.L. Soto, G. Aiza, E. Borràs, F. Kondrashov, A.S. Kondrashov, G.A. Bazykin, L. Valle, European Journal of Human Genetics 32 (2024) 837–845."},"has_accepted_license":"1","department":[{"_id":"FyKo"}],"publication":"European Journal of Human Genetics","doi":"10.1038/s41431-024-01598-8","quality_controlled":"1","pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledgement":"This study was funded by the Spanish Ministry of Science and Innovation (Agencia Estatal de Investigación), co-funded by FEDER funds a way to build Europe [PID2020-112595RB-I00 (LV)], Instituto de Salud Carlos III [CIBERONC CB16/12/00234 (LV); ISCIII-AES-2017 PI17/01082 (JLS), PMP22/00064], Government of Catalonia [AGAUR 2021SGR01112, CERCA Program for institutional support (LV)], Scientific Foundation Asociación Española Contra el Cáncer [AECC Investigador (MT)], Austrian Science Fund FWF [Grant Agreement # I5127-B (FK)], German Research Foundation DFG [Grant Agreement # 429960716 (FK)], and ERC Consolidator [Grant Agreement # 771209 ChrFL (FK)].","scopus_import":"1","file_date_updated":"2025-01-09T09:21:25Z","_id":"15362","ddc":["570"],"oa":1,"day":"01","external_id":{"isi":["001207703200001"],"pmid":["38658779"]},"date_published":"2024-07-01T00:00:00Z","language":[{"iso":"eng"}],"status":"public","year":"2024","publication_status":"published","date_updated":"2026-04-15T08:51:09Z","date_created":"2024-05-05T22:01:04Z","author":[{"first_name":"Maria A.","last_name":"Andrianova","full_name":"Andrianova, Maria A."},{"full_name":"Seplyarskiy, Vladimir B.","last_name":"Seplyarskiy","first_name":"Vladimir B."},{"last_name":"Terradas","first_name":"Mariona","full_name":"Terradas, Mariona"},{"full_name":"Sánchez-Heras, Ana Beatriz","last_name":"Sánchez-Heras","first_name":"Ana Beatriz"},{"full_name":"Mur, Pilar","last_name":"Mur","first_name":"Pilar"},{"full_name":"Soto, José Luis","first_name":"José Luis","last_name":"Soto"},{"full_name":"Aiza, Gemma","last_name":"Aiza","first_name":"Gemma"},{"full_name":"Borràs, Emma","first_name":"Emma","last_name":"Borràs"},{"full_name":"Kondrashov, Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8243-4694","first_name":"Fyodor","last_name":"Kondrashov"},{"full_name":"Kondrashov, Alexey S.","last_name":"Kondrashov","first_name":"Alexey S."},{"full_name":"Bazykin, Georgii A.","last_name":"Bazykin","first_name":"Georgii A."},{"last_name":"Valle","first_name":"Laura","full_name":"Valle, Laura"}],"OA_place":"publisher","ec_funded":1,"volume":32,"publication_identifier":{"issn":["1018-4813"],"eissn":["1476-5438"]},"file":[{"relation":"main_file","content_type":"application/pdf","success":1,"access_level":"open_access","file_size":3060724,"checksum":"e45fc987f4e9ebafdd0ec4f0e9027de4","creator":"dernst","date_created":"2025-01-09T09:21:25Z","file_id":"18799","date_updated":"2025-01-09T09:21:25Z","file_name":"2024_EJHG_Andrianova.pdf"}],"OA_type":"hybrid","isi":1,"intvolume":"        32","article_type":"original"},{"quality_controlled":"1","pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","doi":"10.1038/s41598-022-10827-3","department":[{"_id":"FyKo"}],"publication":"Scientific Reports","has_accepted_license":"1","oa_version":"Published Version","article_number":"6868","citation":{"short":"N. Dranenko, M. Tutukina, M. Gelfand, F. Kondrashov, O. Bochkareva, Scientific Reports 12 (2022).","chicago":"Dranenko, NO, MN Tutukina, MS Gelfand, Fyodor Kondrashov, and Olga Bochkareva. “Chromosome-Encoded IpaH Ubiquitin Ligases Indicate Non-Human Enteroinvasive Escherichia.” <i>Scientific Reports</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41598-022-10827-3\">https://doi.org/10.1038/s41598-022-10827-3</a>.","ista":"Dranenko N, Tutukina M, Gelfand M, Kondrashov F, Bochkareva O. 2022. Chromosome-encoded IpaH ubiquitin ligases indicate non-human enteroinvasive Escherichia. Scientific Reports. 12, 6868.","mla":"Dranenko, NO, et al. “Chromosome-Encoded IpaH Ubiquitin Ligases Indicate Non-Human Enteroinvasive Escherichia.” <i>Scientific Reports</i>, vol. 12, 6868, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41598-022-10827-3\">10.1038/s41598-022-10827-3</a>.","apa":"Dranenko, N., Tutukina, M., Gelfand, M., Kondrashov, F., &#38; Bochkareva, O. (2022). Chromosome-encoded IpaH ubiquitin ligases indicate non-human enteroinvasive Escherichia. <i>Scientific Reports</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41598-022-10827-3\">https://doi.org/10.1038/s41598-022-10827-3</a>","ama":"Dranenko N, Tutukina M, Gelfand M, Kondrashov F, Bochkareva O. Chromosome-encoded IpaH ubiquitin ligases indicate non-human enteroinvasive Escherichia. <i>Scientific Reports</i>. 2022;12. doi:<a href=\"https://doi.org/10.1038/s41598-022-10827-3\">10.1038/s41598-022-10827-3</a>","ieee":"N. Dranenko, M. Tutukina, M. Gelfand, F. Kondrashov, and O. Bochkareva, “Chromosome-encoded IpaH ubiquitin ligases indicate non-human enteroinvasive Escherichia,” <i>Scientific Reports</i>, vol. 12. Springer Nature, 2022."},"type":"journal_article","abstract":[{"lang":"eng","text":"Until recently, Shigella and enteroinvasive Escherichia coli were thought to be primate-restricted pathogens. The base of their pathogenicity is the type 3 secretion system (T3SS) encoded by the pINV virulence plasmid, which facilitates host cell invasion and subsequent proliferation. A large family of T3SS effectors, E3 ubiquitin-ligases encoded by the ipaH genes, have a key role in the Shigella pathogenicity through the modulation of cellular ubiquitination that degrades host proteins. However, recent genomic studies identified ipaH genes in the genomes of Escherichia marmotae, a potential marmot pathogen, and an E. coli extracted from fecal samples of bovine calves, suggesting that non-human hosts may also be infected by these strains, potentially pathogenic to humans. We performed a comparative genomic study of the functional repertoires in the ipaH gene family in Shigella and enteroinvasive Escherichia from human and predicted non-human hosts. We found that fewer than half of Shigella genomes had a complete set of ipaH genes, with frequent gene losses and duplications that were not consistent with the species tree and nomenclature. Non-human host IpaH proteins had a diverse set of substrate-binding domains and, in contrast to the Shigella proteins, two variants of the NEL C-terminal domain. Inconsistencies between strains phylogeny and composition of effectors indicate horizontal gene transfer between E. coli adapted to different hosts. These results provide a framework for understanding of ipaH-mediated host-pathogens interactions and suggest a need for a genomic study of fecal samples from diseased animals."}],"title":"Chromosome-encoded IpaH ubiquitin ligases indicate non-human enteroinvasive Escherichia","corr_author":"1","month":"04","article_processing_charge":"No","project":[{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"name":"Evolutionary analysis of gene regulation","grant_number":"I05127","_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"publisher":"Springer Nature","article_type":"original","intvolume":"        12","isi":1,"publication_identifier":{"issn":["2045-2322"]},"file":[{"checksum":"12601b8a5c6b83bb618f92bcb963ecc9","file_size":3564155,"file_name":"2022_ScientificReports_Dranenko.pdf","date_updated":"2022-05-02T09:05:20Z","file_id":"11349","date_created":"2022-05-02T09:05:20Z","creator":"dernst","content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1}],"ec_funded":1,"volume":12,"publication_status":"published","year":"2022","date_updated":"2026-04-15T08:51:09Z","author":[{"full_name":"Dranenko, NO","last_name":"Dranenko","first_name":"NO"},{"full_name":"Tutukina, MN","first_name":"MN","last_name":"Tutukina"},{"full_name":"Gelfand, MS","last_name":"Gelfand","first_name":"MS"},{"orcid":"0000-0001-8243-4694","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","full_name":"Kondrashov, Fyodor","first_name":"Fyodor","last_name":"Kondrashov"},{"full_name":"Bochkareva, Olga","orcid":"0000-0003-1006-6639","id":"C4558D3C-6102-11E9-A62E-F418E6697425","last_name":"Bochkareva","first_name":"Olga"}],"date_created":"2022-05-02T07:08:42Z","date_published":"2022-04-27T00:00:00Z","external_id":{"isi":["000788639400032"],"pmid":["35477739"]},"language":[{"iso":"eng"}],"status":"public","_id":"11344","oa":1,"ddc":["570"],"day":"27","acknowledgement":"The project was initiated with Aygul Minnegalieva and Yulia Yakovleva at the Summer School of Molecular and Theoretical Biology (SMTB-2020), supported by the Zimin Foundation. We thank Inna Shapovalenko, Daria Abuzova, Elizaveta Kaminskaya, and Dmitriy Zvezdin for their contribution to the project during SMTB-2020. We also thank Peter Vlasov for fruitful discussions.This study was supported by the Russian Foundation for Basic Research (RFBR), Grant # 20-54-14005 and Fonds zur Förderung der wissenschaftlichen Forschung (FWF), Grant # I5127-B. The work of OB is supported by the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement No. 754411. ","scopus_import":"1","file_date_updated":"2022-05-02T09:05:20Z"},{"publication":"Bulletin of Mathematical Biology","has_accepted_license":"1","department":[{"_id":"GradSch"},{"_id":"NiBa"},{"_id":"JaMa"}],"issue":"8","doi":"10.1007/s11538-022-01029-z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"quality_controlled":"1","publisher":"Springer Nature","project":[{"call_identifier":"H2020","name":"Characterizing the fitness landscape on population and global scales","grant_number":"771209","_id":"26580278-B435-11E9-9278-68D0E5697425"},{"name":"Evolutionary analysis of gene regulation","_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181","grant_number":"I05127"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"month":"06","article_processing_charge":"Yes (via OA deal)","corr_author":"1","title":"Relation between the number of peaks and the number of reciprocal sign epistatic interactions","abstract":[{"text":"Empirical essays of fitness landscapes suggest that they may be rugged, that is having multiple fitness peaks. Such fitness landscapes, those that have multiple peaks, necessarily have special local structures, called reciprocal sign epistasis (Poelwijk et al. in J Theor Biol 272:141–144, 2011). Here, we investigate the quantitative relationship between the number of fitness peaks and the number of reciprocal sign epistatic interactions. Previously, it has been shown (Poelwijk et al. in J Theor Biol 272:141–144, 2011) that pairwise reciprocal sign epistasis is a necessary but not sufficient condition for the existence of multiple peaks. Applying discrete Morse theory, which to our knowledge has never been used in this context, we extend this result by giving the minimal number of reciprocal sign epistatic interactions required to create a given number of peaks.","lang":"eng"}],"type":"journal_article","citation":{"chicago":"Saona Urmeneta, Raimundo J, Fyodor Kondrashov, and Kseniia Khudiakova. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” <i>Bulletin of Mathematical Biology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1007/s11538-022-01029-z\">https://doi.org/10.1007/s11538-022-01029-z</a>.","short":"R.J. Saona Urmeneta, F. Kondrashov, K. Khudiakova, Bulletin of Mathematical Biology 84 (2022).","ama":"Saona Urmeneta RJ, Kondrashov F, Khudiakova K. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. <i>Bulletin of Mathematical Biology</i>. 2022;84(8). doi:<a href=\"https://doi.org/10.1007/s11538-022-01029-z\">10.1007/s11538-022-01029-z</a>","ieee":"R. J. Saona Urmeneta, F. Kondrashov, and K. Khudiakova, “Relation between the number of peaks and the number of reciprocal sign epistatic interactions,” <i>Bulletin of Mathematical Biology</i>, vol. 84, no. 8. Springer Nature, 2022.","mla":"Saona Urmeneta, Raimundo J., et al. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” <i>Bulletin of Mathematical Biology</i>, vol. 84, no. 8, 74, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1007/s11538-022-01029-z\">10.1007/s11538-022-01029-z</a>.","apa":"Saona Urmeneta, R. J., Kondrashov, F., &#38; Khudiakova, K. (2022). Relation between the number of peaks and the number of reciprocal sign epistatic interactions. <i>Bulletin of Mathematical Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1007/s11538-022-01029-z\">https://doi.org/10.1007/s11538-022-01029-z</a>","ista":"Saona Urmeneta RJ, Kondrashov F, Khudiakova K. 2022. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. Bulletin of Mathematical Biology. 84(8), 74."},"article_number":"74","oa_version":"Published Version","volume":84,"ec_funded":1,"file":[{"file_size":463025,"checksum":"05a1fe7d10914a00c2bca9b447993a65","creator":"dernst","date_created":"2022-06-20T07:51:32Z","file_id":"11455","date_updated":"2022-06-20T07:51:32Z","file_name":"2022_BulletinMathBiology_Saona.pdf","relation":"main_file","content_type":"application/pdf","success":1,"access_level":"open_access"}],"publication_identifier":{"issn":["0092-8240"],"eissn":["1522-9602"]},"intvolume":"        84","isi":1,"article_type":"original","file_date_updated":"2022-06-20T07:51:32Z","scopus_import":"1","acknowledgement":"We are grateful to Herbert Edelsbrunner and Jeferson Zapata for helpful discussions. Open access funding provided by Austrian Science Fund (FWF). Partially supported by the ERC Consolidator (771209–CharFL) and the FWF Austrian Science Fund (I5127-B) grants to FAK.","day":"17","ddc":["510","570"],"_id":"11447","oa":1,"status":"public","keyword":["Computational Theory and Mathematics","General Agricultural and Biological Sciences","Pharmacology","General Environmental Science","General Biochemistry","Genetics and Molecular Biology","General Mathematics","Immunology","General Neuroscience"],"language":[{"iso":"eng"}],"external_id":{"isi":["000812509800001"],"pmid":["35713756"]},"date_published":"2022-06-17T00:00:00Z","related_material":{"record":[{"relation":"popular_science","status":"private","id":"21918"}],"link":[{"url":"https://doi.org/10.1007/s11538-022-01118-z","relation":"erratum"}]},"author":[{"first_name":"Raimundo J","last_name":"Saona Urmeneta","full_name":"Saona Urmeneta, Raimundo J","id":"BD1DF4C4-D767-11E9-B658-BC13E6697425","orcid":"0000-0001-5103-038X"},{"first_name":"Fyodor","last_name":"Kondrashov","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8243-4694","full_name":"Kondrashov, Fyodor"},{"last_name":"Khudiakova","first_name":"Kseniia","id":"4E6DC800-AE37-11E9-AC72-31CAE5697425","orcid":"0000-0002-6246-1465","full_name":"Khudiakova, Kseniia"}],"date_created":"2022-06-17T16:16:15Z","date_updated":"2026-05-27T06:26:08Z","year":"2022","publication_status":"published"}]