The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Sea anemone MACPF proteins demonstrate an evolutionary transitional state between venomous and developmental functions
Open accessPreprint — published as 10.1093/molbev/msae082 · Paper page
Abstract
Gene duplication is a major force driving evolutionary innovation. A classic example is generating new animal toxins via duplication of physiological protein-encoding genes and recruitment into venom. While this process drives the innovation of many animal venoms, reverse-recruitment of toxins into non-venomous cells remains unresolved. Using comparative genomics, we find members of the Membrane Attack Complex and Perforin Family (MACPF) have been recruited into venom-injecting cells (cnidocytes), in soft and stony corals and sea anemones, suggesting that the ancestral MACPF was a cnidocyte expressed toxin. Further investigation into the model sea anemone Nematostella vectensis, reveals that three members have undergone Nematostella -specific duplications leading to their reverse-recruitment into mesoendodermal cells. Furthermore, simultaneous knock-down of all three mesoendodermally-expressed MACPFs leads to mis-development, supporting that these paralogs have non-venomous function. By resolving the evolutionary history and function of MACPFs in Nematostella , we provide the first proof for reverse-recruitment from venom to organismal development. Significance statement: In this study, we reveal how a gene can gain a new function, even from a most unexpected origin. Specifically, we report that in the last common ancestor of corals and sea anemones a member of the Membrane Attack Complex and Perforin Family (MACPF), which is commonly associated with the immune system, was recruited into venom-injecting cells called cnidocytes. Using the sea anemone Nematostella vectensis we find repeated gene duplication has occurred leading to the new copies adopting divergent functions including being retained in cnidocytes but also recruited into non-venomous mesoendodermal cells. Furthermore, when we deplete Nematostella of mesoendodermally-expressed MACPFs we disrupt normal embryonic development, supporting that these copies have indeed been recruited from venom into the developmental plan.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Flagged first, then by citations
Research works printed but not linked: 60
- 10.2307/1542110 · DOI
- 10.1371/journal.pone.0001121 · DOI
- 10.1126/science.1139158 · DOI · Paper page
- 2016, Genomics and development of Nematostella vectensis and other anthozoans, Current Opinion in Genetics & Development, 39, 63, 10.1016/j.gde.2016.05.024 · DOI
- U. Technau , G. Genikhovich , J. E. M. Kraus , “Cnidaria” in Evolutionary Developmental Biology of Invertebrates 1: Introduction, Non-Bilateria, Acoelomorpha, Xenoturbellida, Chaetognatha, A. Wanninger , Ed. (Springer, 2015), pp. 115–163. · DOI
- 10.1101/2020.10.30.359448 · DOI
- L. Al-Shaer , J. Havrilak , M. J. Layden , “Nematostella vectensis as a Model System” in Handbook of Marine Model Organisms in Experimental Biology, 1st Ed., (CRC Press, 2021), pp. 107–128. · DOI
- 10.1002/wdev.222 · DOI
- 2022, A novel regulatory gene promotes novel cell fate by suppressing ancestral fate in the sea anemone Nematostella vectensis, Proc Natl Acad Sci U S A, 119, e2113701119, 10.1073/pnas.2113701119 · DOI
- 2023, Nematostella vectensis exemplifies the exceptional expansion and diversity of opsins in the eyeless Hexacorallia, Evodevo, 14, 14, 10.1186/s13227-023-00218-8 · DOI
- 10.1242/jeb.110270 · DOI · Paper page
- J. M. Surm , Y. Moran , Insights into how development and life-history dynamics shape the evolution of venom. EvoDevo 12, 1 (2021). · DOI
- 10.1139/z02-135 · DOI
- 10.1016/j.tig.2008.07.001 · DOI
- J. Steger , et al., Single-cell transcriptomics identifies conserved regulators of neuroglandular lineages. Cell Reports 40, 111370 (2022). · DOI
- 2022, Insm1-expressing neurons and secretory cells develop from a common pool of progenitors in the sea anemone Nematostella vectensis, Science Advances, 8, eabi7109, 10.1126/sciadv.abi7109 · DOI
- L. S. Babonis , et al., Single-cell atavism reveals an ancient mechanism of cell type diversification in a sea anemone. Nat Commun 14, 885 (2023). · DOI
- 10.7554/eLife.35014 · DOI
- 2019, The Birth and Death of Toxins with Distinct Functions: A Case Study in the Sea Anemone Nematostella, Molecular Biology and Evolution, 36, 2001, 10.1093/molbev/msz132 · DOI
- K. Sunagar , et al., Cell type-specific expression profiling unravels the development and evolution of stinging cells in sea anemone. BMC Biology 16, 108 (2018). · DOI
- J. M. Surm , et al., Venom tradeoff shapes interspecific interactions, physiology and reproduction. 2023.07.24.550294 (2023). · DOI
- 10.1073/pnas.2011120117 · DOI
- 10.1146/annurev.genom.9.081307.164356 · DOI
- 2012, Dynamic evolution of venom proteins in squamate reptiles, Nature Communications, 3, 1066, 10.1038/ncomms2065 · DOI
- G. Anderluh , M. Kisovec , N. Kraševec , R. J. C. Gilbert , “Distribution of MACPF/CDC Proteins” in MACPF/CDC Proteins - Agents of Defence, Attack and Invasion, Subcellular Biochemistry., G. Anderluh , R. Gilbert , Eds. (Springer Netherlands, 2014), pp. 7–30. · DOI
- 10.1016/S0006-291X(02)00547-8 · DOI
- 10.1016/j.toxicon.2003.11.017 · DOI
- 10.1016/j.toxicon.2007.01.006 · DOI
- 10.1007/s10930-011-9347-8 · DOI
- 2023, Spatial transcriptomics reveals a cnidarian segment polarity program in Nematostella vectensis, Current Biology, 33, 2678, 10.1016/j.cub.2023.05.044 · DOI
- 2023, Molecular insights into the Darwin paradox of coral reefs from the sea anemone Aiptasia, Science Advances, 9, eadf7108, 10.1126/sciadv.adf7108 · DOI
- 10.1038/s41586-020-2385-7 · DOI
- 2021, A stony coral cell atlas illuminates the molecular and cellular basis of coral symbiosis, calcification, and immunity, Cell, 184, 2973, 10.1016/j.cell.2021.04.005 · DOI
- 2022, Histone demethylase Lsd1 is required for the differentiation of neural cells in Nematostella vectensis, Nat Commun, 13, 465, 10.1038/s41467-022-28107-z · DOI
- 10.1242/dev.071902 · DOI · Paper page
- 2020, NvPOU4/Brain3 Functions as a Terminal Selector Gene in the Nervous System of the Cnidarian Nematostella vectensis, Cell Reports, 30, 4473, 10.1016/j.celrep.2020.03.031 · DOI
- 2017, The Membrane Attack Complex/Perforin (MACPF) Superfamily, J Mol Microbiol Biotechnol, 27, 252
- 10.1016/j.tibs.2008.07.004 · DOI
- 2017, Neurodevelopmental MACPFs: The vertebrate astrotactins and BRINPs, Seminars in Cell & Developmental Biology, 72, 171, 10.1016/j.semcdb.2017.05.005 · DOI
- 2017, MACPF/CDC proteins in development: Insights from Drosophila torso-like, Seminars in Cell & Developmental Biology, 72, 163, 10.1016/j.semcdb.2017.05.003 · DOI
- 10.1098/rsob.160053 · DOI
- 10.1038/nature06107 · DOI · Paper page
- 2020, Some like it hot: population-specific adaptations in venom production to abiotic stressors in a widely distributed cnidarian, BMC Biol, 18, 121, 10.1186/s12915-020-00855-8 · DOI
- E. G. Smith , et al., Micro and macroevolution of sea anemone venom phenotype. Nat Commun 14, 249 (2023). · DOI
- 10.1093/bioinformatics/btu170 · DOI · Paper page
- 10.1038/nbt.1883 · DOI
- 2013, De novo transcript sequence reconstruction from RNA-seq using the Trinity platform for reference generation and analysis, Nature Protocols, 8, 1494, 10.1038/nprot.2013.084 · DOI · Paper page
- 10.1093/mol-bev/msab199 · DOI
- 10.1093/MOLBEV/MSAB120 · DOI
- 10.1093/molbev/msu300 · DOI · Paper page
- 10.1093/sysbio/syq010 · DOI · Paper page
- 10.1093/nar/gkw290 · DOI
- 10.1186/s13059-019-1832-y · DOI · Paper page
- V. Solovyev , P. Kosarev , I. Seledsov , D. Vorobyev , Automatic annotation of eukaryotic genes, pseudogenes and promoters. Genome Biology 7, S10 (2006). · DOI
- G. Genikhovich , U. Technau , Induction of Spawning in the Starlet Sea Anemone Nematostella vectensis, In Vitro Fertilization of Gametes, and Dejellying of Zygotes. Cold Spring Harb Protoc 2009, pdb.prot5281 (2009). · DOI
- 10.1016/j.ydbio.2019.01.005 · DOI
- 2021, Functional Characterization of the Cnidarian Antiviral Immune Response Reveals Ancestral Complexity, Molecular Biology and Evolution, 38, 4546, 10.1093/molbev/msab197 · DOI
- G. Genikhovich , U. Technau , In Situ Hybridization of Starlet Sea Anemone (Nematostella vectensis) Embryos, Larvae, and Polyps. Cold Spring Harb Protoc 2009, pdb.prot5282 (2009). · DOI
- 10.1101/gr.162529.113 · DOI
- M. van Kempen , et al., Fast and accurate protein structure search with Foldseek. Nat Biotechnol, 1–4 (2023). · DOI · Paper page
Metadata
- Authors
- Surm, J. M., Landau, M., Columbus-Shenkar, Y. Y., & Moran, Y.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Corresponding author
- Surm, Joachim M.
- Moran, Yehu
- Venue
- Molecular Biology and Evolution
- Publisher
- openRxiv
- Published
- 2023-11-02
- Volume
- 41
- Issue
- 5
- ISSN
- 0737-4038 (ISSN-L)
- PMC
- PMC11090067
- OpenAlex
- W4395958401
- Cited by
- 9
- References
- 1
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 1
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Biology and Evolution (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Israel Science Foundation (636/21)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Marine Invertebrate Physiology and Ecology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Venomous Animal Envenomation and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- membrane attack complex, perforin, sea anemone, Nematostella vectensis, gene duplication, venom evolution, cnidocytes, paralogs, evolutionary innovation
- MeSH terms
- Animals, Cnidarian Venoms, Multigene Family, Phylogeny, Sea Anemones, Evolution, Molecular, Gene Duplication, Perforin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
