{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:10:34Z","timestamp":1790813434291,"version":"4.1.0"},"reference-count":85,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T00:00:00Z","timestamp":1624752000000},"content-version":"am","delay-in-days":345,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:00:00Z","timestamp":1594944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000155","name":"Division of Environmental Biology","doi-asserted-by":"publisher","award":["1638872"],"award-info":[{"award-number":["1638872"]}],"id":[{"id":"10.13039\/100000155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000155","name":"Division of Environmental Biology","doi-asserted-by":"publisher","award":["1711141"],"award-info":[{"award-number":["1711141"]}],"id":[{"id":"10.13039\/100000155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Ecology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Understanding how interspecific interactions mould the molecular basis of adaptations in coevolving species is a long\u2010sought goal of evolutionary biology. Venom in predators and venom resistance proteins in prey are coevolving molecular phenotypes, and while venoms are highly complex mixtures it is unclear if prey respond with equally complex resistance traits. Here, we use a novel molecular methodology based on protein affinity columns to capture and identify candidate blood serum resistance proteins (\u201cvenom interactive proteins\u201d [VIPs]) in California Ground Squirrels (<jats:italic>Otospermophilus beecheyi<\/jats:italic>) that interact with venom proteins from their main predator, Northern Pacific Rattlesnakes (<jats:italic>Crotalus o. oreganus<\/jats:italic>). This assay showed that serum\u2010based resistance is both population\u2010 and species\u2010specific, with serum proteins from ground squirrels showing higher binding affinities for venom proteins of local snakes compared to allopatric individuals. Venom protein specificity assays identified numerous and diverse candidate prey resistance VIPs but also potential targets of venom in prey tissues. Many specific VIPs bind to multiple snake venom proteins and, conversely, single venom proteins bind multiple VIPs, demonstrating that a portion of the squirrel blood serum \u201cresistome\u201d involves broad\u2010based inhibition of nonself proteins and suggests that resistance involves a toxin scavenging mechanism. Analyses of rates of evolution of VIP protein homologues in related mammals show that most of these proteins evolve under purifying selection possibly due to molecular constraints that limit the evolutionary responses of prey to rapidly evolving snake venom proteins. Our method represents a general approach to identify specific proteins involved in co\u2010evolutionary interactions between species at the molecular level.<\/jats:p>","DOI":"10.1111\/mec.15529","type":"journal-article","created":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T21:55:02Z","timestamp":1593294902000},"page":"2871-2888","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["The molecular basis of venom resistance in a rattlesnake\u2010squirrel predator\u2010prey system"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7461-3393","authenticated-orcid":false,"given":"H. Lisle","family":"Gibbs","sequence":"first","affiliation":[{"name":"Department of Evolution, Ecology, and Organismal Biology Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libia","family":"Sanz","sequence":"additional","affiliation":[{"name":"Evolutionary and Translational Venomics Laboratory CSIC Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Evolutionary and Translational Venomics Laboratory CSIC Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Ochoa","sequence":"additional","affiliation":[{"name":"Department of Evolution, Ecology, and Organismal Biology Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa T.B.","family":"Hassinger","sequence":"additional","affiliation":[{"name":"Department of Evolution, Ecology, and Organismal Biology Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3477-3012","authenticated-orcid":false,"given":"Matthew L.","family":"Holding","sequence":"additional","affiliation":[{"name":"Department of Evolution, Ecology, and Organismal Biology Ohio State University Columbus OH USA"},{"name":"Department of Biological Sciences Florida State University Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Calvete","sequence":"additional","affiliation":[{"name":"Evolutionary and Translational Venomics Laboratory CSIC Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-018-0039-1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ympev.2016.07.029"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2017.10.026"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-305X(99)00018-X"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1107808"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2012.1112"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins8090250"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109651"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10886-006-9357-8"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2011.08.009"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1998.2520339.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1586\/epr.11.61"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2018.04.015"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1405484111"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tree.2012.10.020"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00117a015"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.164.3886.1402"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.2004.04228.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1163\/156853993X00542"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1979.0081"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-0101(87)90260-1"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2148-9-146"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1586\/14789450.2015.1073590"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1707727114"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2009.01.020"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2011.12.002"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5258.50"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901224106"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113468109"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.3228405"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1920011117"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12476"},{"key":"e_1_2_7_36_1","volume-title":"Molecular basis of venom resistance in a mammal","author":"Hassinger A. B.","year":"2020"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115116108"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2015.2841"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/icb\/icw082"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/jeb.13347"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2016.01.012"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.201.2.165"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2018.06.084"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1224503"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-646-7_10"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10291"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-6458-3_5"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2008.01059.x"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60392-2"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.57.070188.001541"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200589200"},{"key":"e_1_2_7_52_1","first-page":"259","volume-title":"Reptile venoms and toxins","author":"Neves\u2010Ferreira A. G. C.","year":"2010"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc1854"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2005.02.028"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-0101(98)00205-0"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2012.04.342"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins9050158"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2016.05.003"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-0101(87)90127-9"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00265-015-1957-2"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1230492"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1923"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2002.03308.x"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2016.05.020"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-394"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2015.02.015"},{"key":"e_1_2_7_67_1","doi-asserted-by":"crossref","first-page":"668","DOI":"10.56093\/ijans.v87i6.71348","article-title":"Apolipoproteins in fish: From lipid transport to innate immunity","volume":"87","author":"Sahoo P. K.","year":"2017","journal-title":"Indian Journal of Animal Science"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2012.09.003"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2369"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.200900132"},{"key":"e_1_2_7_71_1","first-page":"1091","article-title":"Inhibition of proteases, myotoxins and phospholipases A2 from Bothrops venoms by the heteromeric protein complex of Didelphis albiventris opossum serum","volume":"43","author":"Soares A. M.","year":"1997","journal-title":"Biochemistry and Molecular Biology International"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-4959(01)00421-3"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.08.005"},{"key":"e_1_2_7_74_1","first-page":"272","volume-title":"The reptiles of Northern and Central Europe","author":"Street D.","year":"1979"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.3.1516"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.022"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1089\/104454902753759717"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1314702110"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-185X.2012.00222.x"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508723103"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5917"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.61.12.5388-5391.1993"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msm088"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msi097"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-4725.2005.31611"},{"key":"e_1_2_7_86_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1098"}],"container-title":["Molecular Ecology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fmec.15529","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mec.15529","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/mec.15529","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1111\/mec.15529","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mec.15529","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T05:22:51Z","timestamp":1693891371000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/mec.15529"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,17]]},"references-count":85,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1111\/mec.15529"],"URL":"https:\/\/doi.org\/10.1111\/mec.15529","archive":["Portico"],"relation":{},"ISSN":["0962-1083","1365-294X"],"issn-type":[{"value":"0962-1083","type":"print"},{"value":"1365-294X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,17]]},"assertion":[{"value":"2019-06-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}