Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals

Nicholas R. Casewell*, Daniel Petras, Daren C. Card, Vivek Suranse, Alexis M. Mychajliw, David Richards, Ivan Koludarov, Laura Oana Albulescu, Julien Slagboom, Benjamin Florian Hempel, Neville M. Ngum, Rosalind J. Kennerley, Jorge L. Brocca, Gareth Whiteley, Robert A. Harrison, Fiona M.S. Bolton, Jordan Debono, Freek J. Vonk, Jessica Alföldi, Jeremy JohnsonElinor K. Karlsson, Kerstin Lindblad-Toh, Ian R. Mellor, Roderich D. Süssmuth, Bryan G. Fry, Sanjaya Kuruppu, Wayne C. Hodgson, Jeroen Kool, Todd A. Castoe, Ian Barnes, Kartik Sunagar, Eivind A.B. Undheim, Samuel T. Turvey

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan solenodon (Solenodon paradoxus). We constructed a genome to underpin proteomic identifications of solenodon venom toxins, before undertaking evolutionary analyses of those constituents, and functional assessments of the secreted venom. Our findings show that solenodon venom consists of multiple paralogous kallikrein 1 (KLK1) serine proteases, which cause hypotensive effects in vivo, and seem likely to have evolved to facilitate vertebrate prey capture. Comparative analyses provide convincing evidence that the oral venom systems of solenodons and shrews have evolved convergently, with the 4 independent origins of venom in eulipotyphlans outnumbering all other venom origins in mammals. We find that KLK1s have been independently coopted into the venom of shrews and solenodons following their divergence during the late Cretaceous, suggesting that evolutionary constraints may be acting on these genes. Consequently, our findings represent a striking example of convergent molecular evolution and demonstrate that distinct structural backgrounds can yield equivalent functions.

Original languageEnglish
Pages (from-to)25745-25755
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number51
Early online date26 Nov 2019
Publication statusPublished - 17 Dec 2019


aCentre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA Liverpool, United Kingdom; bInstitut für Chemie, Technische Universität Berlin, 10623 Berlin, Germany; cCollaborative Mass Spectrometry Innovation Center, University of California, San Diego, La Jolla, CA 92093; dDepartment of Biology, University of Texas at Arlington, Arlington, TX 76010; eDepartment of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138; fMuseum of Comparative Zoology, Harvard University, Cambridge, MA 02138; gEvolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, 560012 Bangalore, India; hDepartment of Biology, Stanford University, Stanford, CA 94305; iDepartment of Rancho La Brea, Natural History Museum of Los Angeles County, Los Angeles, CA 90036; jInstitute of Low Temperature Science, Hokkaido University, 060-0819 Sapporo, Japan; kSchool of Life Sciences, University of Nottingham, University Park, NG7 2RD Nottingham, United Kingdom; lBiomedical Research Centre, University of East Anglia, Norwich Research Park, NR4 7TJ Norwich, United Kingdom; mEcology and Evolution Unit, Okinawa Institute of Science and Technology, Onna, Kunigami-gun, Okinawa, 904-0495, Japan; nDivision of BioAnalytical Chemistry, Amsterdam Institute of Molecules, Medicines and Systems, Vrije Universiteit Amsterdam, 1081 LA Amsterdam, The Netherlands; oDurrell Wildlife Conservation Trust, Les Augres̀ Manor, Trinity, Jersey JE3 5BP, British Channel Islands, United Kingdom; pSOH Conservación, Apto. 401 Residencial Las Galerías, Santo Domingo, 10130, Dominican Republic; qVenom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia, QLD 4067, Australia; rNaturalis Biodiversity Center, 2333 CR Leiden, The Netherlands; sVertebrate Genomics, Broad Institute of MIT and Harvard, Cambridge, MA 02142; tProgram in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01655; uScience for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden; vMonash Venom Group, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, VIC 3800, Australia; wDepartment of Biochemistry & Molecular Biology, Biomedicine Discovery Institute, Monash University, VIC 3800, Australia; xDepartment of Earth Sciences, Natural History Museum, SW7 5BD London, United Kingdom; yCentre for Advanced Imaging, The University of Queensland, Brisbane QLD 4072, Australia; zInstitute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia; aaCentre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, Oslo 0316, Norway; and bbInstitute of Zoology, Zoological Society of London, Regent’s Park, NW1 4RY London, United Kingdom ACKNOWLEDGMENTS. We thank Nicolas Corona, Yimell Corona, Luis Freites, Lisa Casewell, Darren Cook, Diane Genereux, Eva Murén, Voichita Marinescu, Ann-Maree, Kristine Bohmann, Martin Nielsen, Elizabeth Hadly, and the Ministerio de Medio Ambiente y Recursos Naturales (Dominican Republic). This study was supported by the Liverpool School of Tropical Medicine’s Jean Clayton Fund (to N.R.C.); a Sir Henry Dale Fellowship (200517/Z/16/Z to N.R.C.) jointly funded by the Wellcome Trust and the Royal Society; the Deutsche Forschungsgemeinschaft through the Cluster of Excellence Unifying Concepts in Catalysis (to R.D.S.) and Grant PE 2600/1 (to D.P.); a Stanford Center for Computational, Evolutionary, and Human Genomics trainee grant (to A.M.M.); a Distinguished Professor grant from the Swedish Research Council (to K.L.-T.); the Indian Department of Biotechnology Indian Institute of Science (DBT-IISc) Partnership Program (to K.S.); a Department of Science and Technology (DST) INSPIRE Faculty Award (DST/INSPIRE/04/2017/ 000071 to K.S.); the Australian Research Council (DECRA Fellowship DE160101142 to E.A.B.U.); and the Royal Society (Grants RG100902 and UF130573 to S.T.T.).

FundersFunder number
Biotechnology Indian Institute of Science
Ministerio de Medio Ambiente y Recursos Naturales
Stanford Center for Computational
Wellcome Trust
Liverpool School of Tropical Medicine200517/Z/16/Z
Royal Society
Australian Research CouncilDE160101142, RG100902, UF130573
Department of Science and Technology, Ministry of Science and Technology, IndiaDST/INSPIRE/04/2017/ 000071
Deutsche ForschungsgemeinschaftPE 2600/1


    • Convergent molecular evolution
    • Gene duplication
    • Genotype phenotype
    • Kallikrein toxin
    • Venom systems


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