{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:19:30Z","timestamp":1788254370520,"version":"build-2803163510"},"reference-count":65,"publisher":"The Royal Society","issue":"2077","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"US NSF","doi-asserted-by":"crossref","award":["IOS-2209762"],"award-info":[{"award-number":["IOS-2209762"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cornell Hatch","award":["NYC-183408"],"award-info":[{"award-number":["NYC-183408"]}]},{"name":"US Department of Agriculture's National Institute of Food and Agriculture"},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"crossref","award":["1R35GM161912-01"],"award-info":[{"award-number":["1R35GM161912-01"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antagonistic coevolution has long been predicted to leave a macroevolutionary signature of escalating defences in host species. Opposing this classic theory, we previously reported phylogenetic declines in the concentrations of cardenolide toxins among milkweed species in the genus Asclepias. Here we tested the hypothesis of a trade-off between toxin concentration and potency, such that species with lower investment in toxin abundance show higher potency per unit toxin. We tested leaf extracts from more than 50 Asclepias species in vitro against the monarch butterfly's neural Na+\/K+-ATPase, the physiological target of cardenolides. Indeed, in phylogenetically controlled analyses, we found a macroevolutionary trade-off between cardenolide concentration and potency among Asclepias species. Machine learning identified metabolomic features associated with high potency, suggesting triterpenoids that may have a combinatory effect with cardenolides against the butterfly's highly adapted enzyme. Finally, metrics of toxin potency phylogenetically increased over the evolutionary history of Asclepias. This result supports the hypothesis that, in the face of costly defences and toxin-sequestering insect pests, milkweeds evolved low concentrations of more potent toxins, probably along with other plant metabolites that enhance chemical defence. Coevolution may generally drive discordant investment in concentration versus potency of plant chemistry, with defence evolving towards effective and economical strategies.<\/jats:p>","DOI":"10.1098\/rspb.2026.0215","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:05:54Z","timestamp":1787760354000},"source":"Crossref","is-referenced-by-count":1,"title":["Macroevolution of plant defence favours toxin potency over concentration"],"prefix":"10.1098","volume":"293","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4750-8528","authenticated-orcid":false,"given":"Paola","family":"Rubiano-Buitrago","sequence":"first","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, Cornell University 1 , Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2049-7758","authenticated-orcid":false,"given":"Xos\u00e9","family":"L\u00f3pez-Goldar","sequence":"additional","affiliation":[{"name":"Illinois State University School of Biological Sciences 2 , Normal, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy P.","family":"Hastings","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, Cornell University 1 , Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellie","family":"Goud","sequence":"additional","affiliation":[{"name":"Saint Mary's University 3 , Halifax, Nova Scotia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Weber","sequence":"additional","affiliation":[{"name":"Ecology and Evolutionary Biology, University of Michigan 4 , Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anurag A.","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, Cornell University 1 , Ithaca, NY, USA"},{"name":"Department of Entomology, Cornell University 5 , Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"2026090104561577900_RSPB20260215C1","volume-title":"Avoiding attack: the evolutionary ecology of crypsis, aposematism, and mimicry","author":"Ruxton","year":"2019","edition":"2nd edn"},{"key":"2026090104561577900_RSPB20260215C2","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev-arplant-042916-040856","article-title":"Trade-offs between plant growth and defense against insect herbivory: an emerging mechanistic synthesis","volume":"68","author":"Z\u00fcst","year":"2017","journal-title":"Annu. 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