{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:07:04Z","timestamp":1792786024608,"version":"4.5.0"},"reference-count":106,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2019\/34\/A\/NZ8\/00231"],"award-info":[{"award-number":["2019\/34\/A\/NZ8\/00231"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MEYS CZ","award":["LUAUS25009"],"award-info":[{"award-number":["LUAUS25009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Host\u2013parasite co-evolution drives the diversification of host immune genes involved in the recognition of pathogen antigens and molecular patterns. In contrast, the immune genes involved in self-recognition and inhibition of immune responses against self-cells (missing-self immunity) may be evolutionarily constrained by the need to interact with self-components. However, many pathogens, such as the Lyme disease agent Borrelia, hijack these genes to evade the immune system and may therefore select for their diversification. How these contrasting but concurrent selective forces shape the evolution of missing-self regulators is not clearly understood. To fill this gap, we investigated polymorphism and molecular signatures of selection acting on a missing-self regulator, the complement factor H (CFH), in bank vole populations, which are an important wild reservoir for Borrelia. We then compared the geographic structuring in the CFH domain interacting with Borrelia (CCP 20) against a genomic background represented by RAD-seq markers. We found signals of positive and diversifying selection at CCP 20, suggesting that CFH evolved in response to pressures from pathogens. Additionally, we found other innate immunity genes within the alternative complement pathway, which is regulated by CFH, under diversifying selection, highlighting its involvement in host\u2013parasite coevolution. This study demonstrates that an innate missing-self sensor in a wild vertebrate is under diversifying selection, likely driven by pathogens.<\/jats:p>","DOI":"10.1093\/molbev\/msag082","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T11:42:13Z","timestamp":1775216533000},"source":"Crossref","is-referenced-by-count":2,"title":["A key regulator of missing-self innate immunity is polymorphic and under diversifying selection"],"prefix":"10.1093","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9860-6497","authenticated-orcid":false,"given":"Rocco F","family":"Notarnicola","sequence":"first","affiliation":[{"name":"Evolutionary Biology Group, Adam Mickiewicz University , Pozna\u0144 ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6593-3256","authenticated-orcid":false,"given":"Magdalena","family":"Herdegen-Radwan","sequence":"additional","affiliation":[{"name":"Department of Behavioural Ecology, Adam Mickiewicz University , Pozna\u0144 ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5550-9398","authenticated-orcid":false,"given":"Joanna","family":"R\u00f3\u017ca\u0144ska-Wr\u00f3bel","sequence":"additional","affiliation":[{"name":"Evolutionary Biology Group, Adam Mickiewicz University , Pozna\u0144 ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7691-8075","authenticated-orcid":false,"given":"Mateusz","family":"Konczal","sequence":"additional","affiliation":[{"name":"Evolutionary Biology Group, Adam Mickiewicz University , Pozna\u0144 ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8952-5361","authenticated-orcid":false,"given":"Karolina","family":"Przesmycka","sequence":"additional","affiliation":[{"name":"Evolutionary Biology Group, Adam Mickiewicz University , Pozna\u0144 ,","place":["Poland"]},{"name":"Centre for Ecology and Conservation, University of Exeter , Penryn ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9429-0667","authenticated-orcid":false,"given":"Petr","family":"Kotl\u00edk","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Ecology, Institute of Animal Physiology and Genetics of the Czech Academy of Sciences , Lib\u011bchov ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1698-6615","authenticated-orcid":false,"given":"Wies\u0142aw","family":"Babik","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Jagiellonian University, Institute of Environmental Sciences , Krak\u00f3w ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8503-5701","authenticated-orcid":false,"given":"Jacek","family":"Radwan","sequence":"additional","affiliation":[{"name":"Evolutionary Biology Group, Adam Mickiewicz University , Pozna\u0144 ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"2026042215104425900_msag082-B1","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1186\/1471-2105-12-246","article-title":"Enhancements to the ADMIXTURE algorithm for individual ancestry estimation","volume":"12","author":"Alexander","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2026042215104425900_msag082-B2","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1101\/gr.094052.109","article-title":"Fast model-based estimation of ancestry in unrelated individuals","volume":"19","author":"Alexander","year":"2009","journal-title":"Genome Res."},{"key":"2026042215104425900_msag082-B3","author":"Andrews","year":"2010"},{"key":"2026042215104425900_msag082-B4","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1615\/CritRevImmunol.v17.i2.40","article-title":"The nature of selection on the major histocompatibility complex","volume":"17","author":"Apanius","year":"1997","journal-title":"Crit Rev Immunol."},{"key":"2026042215104425900_msag082-B5","doi-asserted-by":"publisher","first-page":"e7724","DOI":"10.7717\/peerj.7724","article-title":"Adapterama III: quadruple-indexed, double\/triple-enzyme RADseq libraries (2RAD\/3RAD)","volume":"7","author":"Bayona-V\u00e1squez","year":"2019","journal-title":"PeerJ"},{"key":"2026042215104425900_msag082-B6","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1111\/j.1365-294X.2004.02125.x","article-title":"Identifying adaptive genetic divergence among populations from genome scans","volume":"13","author":"Beaumont","year":"2004","journal-title":"Mol Ecol."},{"key":"2026042215104425900_msag082-B7","doi-asserted-by":"publisher","first-page":"2817","DOI":"10.1093\/bioinformatics\/btw327","article-title":"Pong: fast analysis and visualization of latent clusters in population genetic data","volume":"32","author":"Behr","year":"2016","journal-title":"Bioinformatics"},{"key":"2026042215104425900_msag082-B8","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1046\/j.1420-9101.2003.00531.x","article-title":"MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years?","volume":"16","author":"Bernatchez","year":"2003","journal-title":"J Evol Biol."},{"key":"2026042215104425900_msag082-B9","doi-asserted-by":"publisher","first-page":"18685","DOI":"10.1074\/jbc.M113.459040","article-title":"Structural basis for complement evasion by Lyme disease pathogen Borrelia burgdorferi","volume":"288","author":"Bhattacharjee","year":"2013","journal-title":"J Biol Chem."},{"key":"2026042215104425900_msag082-B10","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/237139a0","article-title":"Evolutionary significance of the HL-A system","volume":"237","author":"Bodmer","year":"1972","journal-title":"Nature"},{"key":"2026042215104425900_msag082-B11","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"2026042215104425900_msag082-B12","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1111\/mec.13558","article-title":"The mammalian complement system as an epitome of host-pathogen genetic conflicts","volume":"25","author":"Cagliani","year":"2016","journal-title":"Mol Ecol."},{"key":"2026042215104425900_msag082-B13","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1093\/molbev\/msv096","article-title":"A coevolutionary arms race between hosts and viruses drives polymorphism and polygenicity of NK cell receptors","volume":"32","author":"Carrillo-Bustamante","year":"2015","journal-title":"Mol Biol Evol."},{"key":"2026042215104425900_msag082-B14","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00251-015-0869-7","article-title":"The evolution of natural killer cell receptors","volume":"68","author":"Carrillo-Bustamante","year":"2016","journal-title":"Immunogenetics"},{"key":"2026042215104425900_msag082-B15","doi-asserted-by":"publisher","first-page":"3124","DOI":"10.1111\/mec.12354","article-title":"Stacks: an analysis tool set for population genomics","volume":"22","author":"Catchen","year":"2013","journal-title":"Mol Ecol."},{"key":"2026042215104425900_msag082-B16","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"GigaScience"},{"key":"2026042215104425900_msag082-B17","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1093\/bioinformatics\/btr330","article-title":"The variant call format and VCFtools","volume":"27","author":"Danecek","year":"2011","journal-title":"Bioinformatics"},{"key":"2026042215104425900_msag082-B18","author":"Deraad"},{"key":"2026042215104425900_msag082-B19","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1111\/1755-0998.13618","article-title":"SNPfiltR: an R package for interactive and reproducible SNP filtering","volume":"22","author":"Deraad","year":"2022","journal-title":"Molecular Ecology Resources"},{"key":"2026042215104425900_msag082-B20","doi-asserted-by":"publisher","first-page":"e11484","DOI":"10.1002\/aps3.11484","article-title":"Long-read genotyping with SLANG (simple long-read loci assembly of nanopore data for genotyping)","volume":"10","author":"Dorfner","year":"2022","journal-title":"Appl Plant Sci."},{"key":"2026042215104425900_msag082-B21","doi-asserted-by":"publisher","author":"Driller","year":"2020","DOI":"10.1101\/2020.04.03.024331"},{"key":"2026042215104425900_msag082-B22","doi-asserted-by":"publisher","first-page":"e1004627","DOI":"10.1371\/journal.pcbi.1004627","article-title":"Red queen processes drive positive selection on major histocompatibility complex (MHC) genes","volume":"11","author":"Ejsmond","year":"2015","journal-title":"PLoS Comput Biol."},{"key":"2026042215104425900_msag082-B23","doi-asserted-by":"publisher","first-page":"e12469","DOI":"10.7554\/eLife.12469","article-title":"Viruses are a dominant driver of protein adaptation in mammals","volume":"5","author":"Enard","year":"2016","journal-title":"eLife"},{"key":"2026042215104425900_msag082-B24","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.molimm.2017.01.015","article-title":"Potential influences of complement factor H in autoimmune inflammatory and thrombotic disorders","volume":"84","author":"Ferluga","year":"2017","journal-title":"Mol Immunol."},{"key":"2026042215104425900_msag082-B25","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jmb.2010.07.029","article-title":"Molecular basis for complement recognition and inhibition determined by crystallographic studies of the staphylococcal complement inhibitor (SCIN) bound to C3c and C3b","volume":"402","author":"Garcia","year":"2010","journal-title":"J Mol Biol."},{"key":"2026042215104425900_msag082-B26","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1111\/j.0014-3820.2003.tb00580.x","article-title":"Perspective: detecting adaptive molecular polymorphism, lessons from the MHC","volume":"57","author":"Garrigan","year":"2003","journal-title":"Evolution"},{"key":"2026042215104425900_msag082-B27","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1534\/genetics.115.181453","article-title":"Genome-wide scan for adaptive divergence and association with population-specific covariates","volume":"201","author":"Gautier","year":"2015","journal-title":"Genetics"},{"key":"2026042215104425900_msag082-B28","doi-asserted-by":"publisher","first-page":"101627","DOI":"10.1016\/j.smim.2022.101627","article-title":"Complement component C3: a structural perspective and potential therapeutic implications","volume":"59","author":"Geisbrecht","year":"2022","journal-title":"Semin Immunol."},{"key":"2026042215104425900_msag082-B29","doi-asserted-by":"publisher","first-page":"e84315","DOI":"10.7554\/eLife.84315","article-title":"A meta-analysis of genome-wide association studies of childhood wheezing phenotypes identifies ANXA1 as a susceptibility locus for persistent wheezing","volume":"12","author":"Granell","year":"2023","journal-title":"eLife"},{"key":"2026042215104425900_msag082-B30","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.3390\/ani10101820","article-title":"Zoonotic viruses in three species of voles from Poland","volume":"10","author":"Grzybek","year":"2020","journal-title":"Animals (Basel)."},{"key":"2026042215104425900_msag082-B31","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1534\/genetics.113.152462","article-title":"Robust identification of local adaptation from allele frequencies","volume":"195","author":"G\u00fcnther","year":"2013","journal-title":"Genetics"},{"key":"2026042215104425900_msag082-B32","first-page":"95","article-title":"BioEdit: A User-Friendly Biological Sequence Alignment Editor and Analysis Program for Windows 95\/98\/NT","volume":"41","author":"Hall","year":"1999","journal-title":"Nucleic Acids Symposium Series"},{"key":"2026042215104425900_msag082-B33","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1017\/S0031182002002548","article-title":"Association of Borrelia afzelii with rodents in Europe","volume":"126","author":"Hanincov\u00e1","year":"2003","journal-title":"Parasitology"},{"key":"2026042215104425900_msag082-B34","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/335167a0","article-title":"Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection","volume":"335","author":"Hughes","year":"1988","journal-title":"Nature"},{"key":"2026042215104425900_msag082-B35","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1073\/pnas.86.3.958","article-title":"Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection","volume":"86","author":"Hughes","year":"1989","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2026042215104425900_msag082-B36","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1017\/S0031182098003564","article-title":"Transmission of Borrelia afzelii from Apodemus mice and Clethrionomys voles to Ixodes ricinus ticks: differential transmission pattern and overwintering maintenance","volume":"118","author":"Humair","year":"1999","journal-title":"Parasitology"},{"key":"2026042215104425900_msag082-B37","doi-asserted-by":"publisher","first-page":"20170963","DOI":"10.1098\/rsif.2017.0963","article-title":"Playing \u201chide-and-seek\u201d with factor H: game-theoretical analysis of a single nucleotide polymorphism","volume":"15","author":"Hummert","year":"2018","journal-title":"J R Soc Interface."},{"key":"2026042215104425900_msag082-B38","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1111\/1755-0998.13843","article-title":"A comprehensive framework for detecting copy number variants from single nucleotide polymorphism data: \u201crCNV\u201d, a versatile R package for paralogue and CNV detection","volume":"23","author":"Karunarathne","year":"2023","journal-title":"Mol Ecol Resour."},{"key":"2026042215104425900_msag082-B39","author":"Kassambara"},{"key":"2026042215104425900_msag082-B40","doi-asserted-by":"publisher","first-page":"8361","DOI":"10.1038\/s41598-018-26672-2","article-title":"Signatures of balancing selection in toll-like receptor (TLRs) genes \u2013 novel insights from a free-living rodent","volume":"8","author":"Kloch","year":"2018","journal-title":"Sci Rep."},{"key":"2026042215104425900_msag082-B41","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/1755-0998.12549","article-title":"VCFR: a package to manipulate and visualize variant call format data in R","volume":"17","author":"Knaus","year":"2017","journal-title":"Mol Ecol Resour."},{"key":"2026042215104425900_msag082-B42","doi-asserted-by":"publisher","first-page":"e0135996","DOI":"10.1371\/journal.pone.0135996","article-title":"A newly-identified polymorphism in rhesus macaque complement factor H modulates binding affinity for meningococcal FHbp","volume":"10","author":"Konar","year":"2015","journal-title":"PLoS One"},{"key":"2026042215104425900_msag082-B43","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1093\/molbev\/msl051","article-title":"Automated phylogenetic detection of recombination using a genetic algorithm","volume":"23","author":"Kosakovsky Pond","year":"2006","journal-title":"Mol Biol Evol."},{"key":"2026042215104425900_msag082-B44","doi-asserted-by":"publisher","first-page":"14860","DOI":"10.1073\/pnas.0603237103","article-title":"A northern glacial refugium for bank voles (Clethrionomys glareolus)","volume":"103","author":"Kotlik","year":"2006","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2026042215104425900_msag082-B45","doi-asserted-by":"publisher","first-page":"5112","DOI":"10.1128\/AEM.01043-13","article-title":"Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform","volume":"79","author":"Kozich","year":"2013","journal-title":"Appl Environ Microbiol."},{"key":"2026042215104425900_msag082-B46","doi-asserted-by":"publisher","first-page":"2421","DOI":"10.1074\/jbc.M308343200","article-title":"Complement resistance of Borrelia burgdorferi correlates with the expression of BbCRASP-1, a novel linear plasmid-encoded surface protein that interacts with human factor H and FHL-1 and is unrelated to Erp proteins","volume":"279","author":"Kraiczy","year":"2004","journal-title":"J Biol Chem."},{"key":"2026042215104425900_msag082-B47","doi-asserted-by":"publisher","first-page":"msac174","DOI":"10.1093\/molbev\/msac174","article-title":"TimeTree 5. An expanded resource for species divergence times","volume":"39","author":"Kumar","year":"2022","journal-title":"Mol Biol Evol."},{"key":"2026042215104425900_msag082-B48","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.2174\/156652412802480925","article-title":"Structure, function and control of complement C5 and its proteolytic fragments","volume":"12","author":"Laursen","year":"2012","journal-title":"Curr Mol Med."},{"key":"2026042215104425900_msag082-B49","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence alignment\/map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2026042215104425900_msag082-B50","author":"Li","year":"2013"},{"key":"2026042215104425900_msag082-B51","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1111\/mec.15459","article-title":"Balancing selection in pattern recognition receptor signalling pathways is associated with gene function and pleiotropy in a wild rodent","volume":"29","author":"Lundberg","year":"2020","journal-title":"Mol Ecol."},{"key":"2026042215104425900_msag082-B52","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.molimm.2013.05.218","article-title":"Complement and innate immune evasion strategies of the human pathogenic fungus Candida albicans","volume":"56","author":"Luo","year":"2013","journal-title":"Mol Immunol."},{"key":"2026042215104425900_msag082-B53","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1111\/mec.15427","article-title":"High genomic diversity in the bank vole at the northern apex of a range expansion: the role of multiple colonizations and end-glacial refugia","volume":"29","author":"Markov\u00e1","year":"2020","journal-title":"Mol Ecol."},{"key":"2026042215104425900_msag082-B54","doi-asserted-by":"publisher","first-page":"7840","DOI":"10.1038\/s41467-023-43383-z","article-title":"Local adaptation and future climate vulnerability in a wild rodent","volume":"14","author":"Markov\u00e1","year":"2023","journal-title":"Nat Commun."},{"key":"2026042215104425900_msag082-B55","doi-asserted-by":"publisher","author":"McDougal","year":"2024","DOI":"10.1101\/2024.05.13.593954"},{"key":"2026042215104425900_msag082-B56","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1111\/1755-0998.12613","article-title":"Paralogs are revealed by proportion of heterozygotes and deviations in read ratios in genotyping-by-sequencing data from natural populations","volume":"17","author":"McKinney","year":"2017","journal-title":"Mol Ecol Resour."},{"key":"2026042215104425900_msag082-B57","doi-asserted-by":"publisher","first-page":"2418","DOI":"10.1002\/1873-3468.12284","article-title":"Self-nonself discrimination by the complement system","volume":"590","author":"Meri","year":"2016","journal-title":"FEBS Lett."},{"key":"2026042215104425900_msag082-B58","doi-asserted-by":"publisher","first-page":"e1003308","DOI":"10.1371\/annotation\/41169409-3260-4295-baf4-a1a4621a8e48","article-title":"Microbes bind complement inhibitor factor H via a common site","volume":"9","author":"Meri","year":"2013","journal-title":"PLoS Pathog."},{"key":"2026042215104425900_msag082-B59","doi-asserted-by":"publisher","first-page":"3400","DOI":"10.1111\/mec.16486","article-title":"Long-term patterns of association between MHC and helminth burdens in the bank vole support red queen dynamics","volume":"31","author":"Migalska","year":"2022","journal-title":"Mol Ecol."},{"key":"2026042215104425900_msag082-B60","doi-asserted-by":"publisher","first-page":"msac102","DOI":"10.1093\/molbev\/msac102","article-title":"Selection balancing at innate immune genes: adaptive polymorphism maintenance in toll-like receptors","volume":"39","author":"Minias","year":"2022","journal-title":"Mol Biol Evol."},{"key":"2026042215104425900_msag082-B61","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/S0277-3791(00)00145-1","article-title":"Environmental processes of the ice age: land, oceans, glaciers (EPILOG)","volume":"20","author":"Mix","year":"2001","journal-title":"Quat Sci Rev."},{"key":"2026042215104425900_msag082-B62","doi-asserted-by":"publisher","first-page":"e1002764","DOI":"10.1371\/journal.pgen.1002764","article-title":"Detecting individual sites subject to episodic diversifying selection","volume":"8","author":"Murrell","year":"2012","journal-title":"PLoS Genet."},{"key":"2026042215104425900_msag082-B63","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12862-023-02122-0","article-title":"Balancing selection on the complement system of a wild rodent","volume":"23","author":"Nandakumar","year":"2023","journal-title":"BMC Ecol Evol."},{"key":"2026042215104425900_msag082-B64","doi-asserted-by":"crossref","DOI":"10.7312\/nei-92038","volume-title":"Molecular evolutionary genetics","author":"Nei","year":"1987"},{"key":"2026042215104425900_msag082-B65","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1093\/oxfordjournals.molbev.a040410","article-title":"Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions","volume":"3","author":"Nei","year":"1986","journal-title":"Mol Biol Evol."},{"key":"2026042215104425900_msag082-B66","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41437-023-00600-1","article-title":"Different waves of postglacial recolonisation and genomic structure of bank vole populations in NE Poland","volume":"130","author":"Niedzia\u0142kowska","year":"2023","journal-title":"Heredity"},{"key":"2026042215104425900_msag082-B67","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1007\/s00251-006-0142-1","article-title":"Genomic view of the evolution of the complement system","volume":"58","author":"Nonaka","year":"2006","journal-title":"Immunogenetics"},{"key":"2026042215104425900_msag082-B68","doi-asserted-by":"publisher","first-page":"e1000698","DOI":"10.1371\/journal.pgen.1000698","article-title":"Quantifying adaptive evolution in the Drosophila immune system","volume":"5","author":"Obbard","year":"2009","journal-title":"PLoS Genet."},{"key":"2026042215104425900_msag082-B69","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1093\/bioinformatics\/btp696","article-title":"Pegas: an R package for population genetics with an integrated\u2013modular approach.","volume":"26","author":"Paradis","year":"2010","journal-title":"Bioinformatics"},{"key":"2026042215104425900_msag082-B70","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1111\/2041-210X.12775","article-title":"Lost in parameter space: a road map for STACKS","volume":"8","author":"Paris","year":"2017","journal-title":"Methods Ecol Evol."},{"key":"2026042215104425900_msag082-B71","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.1111\/mec.16887","article-title":"Large effective population size masks population genetic structure in Hirondellea amphipods within the deepest marine ecosystem, the Mariana Trench","volume":"32","author":"Piertney","year":"2023","journal-title":"Mol Ecol."},{"key":"2026042215104425900_msag082-B72","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.molimm.2015.03.011","article-title":"Of mice and men: the factor H protein family and complement regulation","volume":"67","author":"Pouw","year":"2015","journal-title":"Mol Immunol."},{"key":"2026042215104425900_msag082-B73","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"2026042215104425900_msag082-B74","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.tig.2020.01.008","article-title":"Advances in the evolutionary understanding of MHC polymorphism","volume":"36","author":"Radwan","year":"2020","journal-title":"Trends Genet."},{"key":"2026042215104425900_msag082-B75","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0022594","article-title":"MACSE: multiple alignment of coding SEquences accounting for frameshifts and stop codons","author":"Ranwez","year":"2011","journal-title":"PLoS One"},{"key":"2026042215104425900_msag082-B76","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2022"},{"key":"2026042215104425900_msag082-B77","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/s41577-019-0168-x","article-title":"New insights into the immune functions of complement","volume":"19","author":"Reis","year":"2019","journal-title":"Nat Rev Immunol."},{"key":"2026042215104425900_msag082-B78","doi-asserted-by":"publisher","first-page":"2640","DOI":"10.1038\/nprot.2017.123","article-title":"Deriving genotypes from RAD-seq short-read data using stacks","volume":"12","author":"Rochette","year":"2017","journal-title":"Nat Protoc."},{"key":"2026042215104425900_msag082-B79","doi-asserted-by":"publisher","first-page":"e00146","DOI":"10.1042\/BSR20140117","article-title":"New functional and structural insights from updated mutational databases for complement factor H, factor I, membrane cofactor protein and C3","volume":"34","author":"Rodriguez","year":"2014","journal-title":"Biosci Rep."},{"key":"2026042215104425900_msag082-B80","doi-asserted-by":"publisher","first-page":"e2584","DOI":"10.7717\/peerj.2584","article-title":"VSEARCH: a versatile open source tool for metagenomics","volume":"4","author":"Rognes","year":"2016","journal-title":"PeerJ"},{"key":"2026042215104425900_msag082-B81","doi-asserted-by":"publisher","first-page":"e17534","DOI":"10.1111\/mec.17534","article-title":"Interplay between vertebrate adaptive immunity and bacterial infectivity genes: bank vole MHC versus Borrelia afzelii OspC","volume":"33","author":"R\u00f3\u017ca\u0144ska-Wr\u00f3bel","year":"2025","journal-title":"Mol Ecol."},{"key":"2026042215104425900_msag082-B82","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1017\/S0016672300004547","article-title":"The effect of hitchhiking on genes linked to a balanced polymorphism in a subdivided population","volume":"76","author":"Schierup","year":"2000","journal-title":"Genetic Research"},{"key":"2026042215104425900_msag082-B83","doi-asserted-by":"publisher","first-page":"2610","DOI":"10.4049\/jimmunol.181.4.2610","article-title":"A new map of glycosaminoglycan and C3b binding sites on factor H","volume":"181","author":"Schmidt","year":"2008","journal-title":"The Journal of Immunology"},{"key":"2026042215104425900_msag082-B84","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1111\/imr.12475","article-title":"Protection of host cells by complement regulators","volume":"274","author":"Schmidt","year":"2016","journal-title":"Immunol Rev."},{"key":"2026042215104425900_msag082-B85","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1111\/1755-0998.12453","article-title":"AMPLISAS: a web server for multilocus genotyping using next-generation amplicon sequencing data","volume":"16","author":"Sebastian","year":"2016","journal-title":"Mol Ecol Resour."},{"key":"2026042215104425900_msag082-B86","doi-asserted-by":"publisher","first-page":"e0163962","DOI":"10.1371\/journal.pone.0163962","article-title":"SeqKit: a cross-platform and ultrafast toolkit for FASTA\/Q file manipulation","volume":"11","author":"Shen","year":"2016","journal-title":"PLoS One"},{"key":"2026042215104425900_msag082-B87","doi-asserted-by":"publisher","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"2026042215104425900_msag082-B88","doi-asserted-by":"publisher","first-page":"e41815","DOI":"10.7554\/eLife.41815","article-title":"Immune genes are hotspots of shared positive selection across birds and mammals","volume":"8","author":"Shultz","year":"2019","journal-title":"eLife"},{"key":"2026042215104425900_msag082-B89","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1093\/molbev\/msv022","article-title":"Less is more: an adaptive branch-site random effects model for efficient detection of episodic diversifying selection","volume":"32","author":"Smith","year":"2015","journal-title":"Molecular biology and evolution"},{"key":"2026042215104425900_msag082-B90","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1098\/rspb.2009.2084","article-title":"How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings","volume":"277","author":"Spurgin","year":"2010","journal-title":"Proc Biol Sci."},{"key":"2026042215104425900_msag082-B91","doi-asserted-by":"publisher","first-page":"3022","DOI":"10.1093\/molbev\/msab120","article-title":"MEGA11: molecular evolutionary genetics analysis version 11","volume":"38","author":"Tamura","year":"2021","journal-title":"Mol Biol Evol."},{"key":"2026042215104425900_msag082-B92","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1007\/s00239-018-9832-1","article-title":"Divergent selection of pattern recognition receptors in mammals with different ecological characteristics","volume":"86","author":"Tian","year":"2018","journal-title":"J Mol Evol."},{"key":"2026042215104425900_msag082-B93","doi-asserted-by":"publisher","first-page":"2050313X","DOI":"10.1177\/2050313X231186496","article-title":"A case of Chopra-Amiel-Gordon syndrome with a novel heterozygous variant in the ANKRD17 gene: a case report","volume":"11","author":"Tinatin","year":"2023","journal-title":"SAGE Open Med Case Rep."},{"key":"2026042215104425900_msag082-B94","doi-asserted-by":"publisher","first-page":"20130364","DOI":"10.1098\/rspb.2013.0364","article-title":"Polymorphisms at the innate immune receptor TLR2 are associated with Borrelia infection in a wild rodent population","volume":"280","author":"Tschirren","year":"2013","journal-title":"Proc Biol Sci."},{"key":"2026042215104425900_msag082-B95","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s13071-015-1257-8","article-title":"Multi-trophic interactions driving the transmission cycle of Borrelia afzelii between Ixodes ricinus and rodents: a review","volume":"8","author":"van Duijvendijk","year":"2015","journal-title":"Parasit Vectors."},{"key":"2026042215104425900_msag082-B96","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.21873\/invivo.12059","article-title":"The role of SNPs in IL1RL1 and IL1RAP genes in age-related macular degeneration development and treatment efficacy","volume":"34","author":"Vilkeviciute","year":"2020","journal-title":"In Vivo"},{"key":"2026042215104425900_msag082-B97","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1111\/j.1420-9101.2004.00711.x","article-title":"Between-year variation of MHC allele frequencies in great reed warblers: selection or drift?","volume":"17","author":"Westerdahl","year":"2004","journal-title":"J Evol Biol."},{"key":"2026042215104425900_msag082-B98","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1093\/molbev\/msp018","article-title":"A history of recurrent positive selection at the toll-like receptor 5 in primates","volume":"26","author":"Wlasiuk","year":"2009","journal-title":"Mol Biol Evol."},{"key":"2026042215104425900_msag082-B99","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1111\/j.1469-7998.2010.00699.x","article-title":"Phylogeographic signatures of northward post-glacial colonization from high-latitude refugia: a case study of bank voles using museum specimens","volume":"281","author":"W\u00f3jcik","year":"2010","journal-title":"J Zool."},{"key":"2026042215104425900_msag082-B100","doi-asserted-by":"publisher","first-page":"101766","DOI":"10.1016\/j.ttbdis.2021.101766","article-title":"Host association of Borrelia burgdorferi sensu lato: a review","volume":"12","author":"Wolcott","year":"2021","journal-title":"Ticks Tick Borne Dis."},{"key":"2026042215104425900_msag082-B101","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/ng1202-569","article-title":"Biological and biomedical implications of the co-evolution of pathogens and their hosts","volume":"32","author":"Woolhouse","year":"2002","journal-title":"Nat Genet."},{"key":"2026042215104425900_msag082-B102","doi-asserted-by":"publisher","first-page":"e1012994","DOI":"10.1371\/journal.ppat.1012994","article-title":"A poxvirus ankyrin protein LSDV012 inhibits IFIT1 in a host-species-specific manner by compromising its RNA binding ability","volume":"21","author":"Xie","year":"2025","journal-title":"PLoS Pathog."},{"key":"2026042215104425900_msag082-B103","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1093\/molbev\/msm088","article-title":"PAML 4: phylogenetic analysis by Maximum likelihood","volume":"24","author":"Yang","year":"2007","journal-title":"Mol Biol Evol."},{"key":"2026042215104425900_msag082-B104","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/s00011-019-01307-y","article-title":"Associations of IL1RAP and IL1RL1 gene polymorphisms with obesity and inflammation mediators","volume":"69","author":"Yu","year":"2020","journal-title":"Inflammation Research"},{"key":"2026042215104425900_msag082-B105","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/imr.13147","article-title":"C3-dependent effector functions of complement","volume":"313","author":"Zarantonello","year":"2023","journal-title":"Immunol Rev."},{"key":"2026042215104425900_msag082-B106","doi-asserted-by":"publisher","first-page":"evab023","DOI":"10.1093\/gbe\/evab023","article-title":"Divergence in coding sequence and expression of different functional categories of immune genes between two wild rodent Species","volume":"13","author":"Zhong","year":"2021","journal-title":"Genome Biol Evol."}],"container-title":["Molecular Biology and Evolution"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/mbe\/advance-article-pdf\/doi\/10.1093\/molbev\/msag082\/67871482\/msag082.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mbe\/article-pdf\/43\/4\/msag082\/67871482\/msag082.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mbe\/article-pdf\/43\/4\/msag082\/67871482\/msag082.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T19:10:50Z","timestamp":1776885050000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mbe\/article\/doi\/10.1093\/molbev\/msag082\/8607784"}},"subtitle":[],"editor":[{"given":"Diogo","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":106,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,1]]}},"URL":"https:\/\/doi.org\/10.1093\/molbev\/msag082","relation":{"has-preprint":[{"id-type":"doi","id":"10.64898\/2025.12.10.693425","asserted-by":"object"}]},"ISSN":["0737-4038","1537-1719"],"issn-type":[{"value":"0737-4038","type":"print"},{"value":"1537-1719","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,4,1]]},"article-number":"msag082"}}