Abstract
Domestication has profoundly influenced the evolution of plant metabolism, shaping the balance between productivity and ecological resilience. To explore the biochemical consequences of this process, we performed an integrative metabolomic comparison between the domesticated Sechium edule var. albus minor and its wild relative S. edule 653-d. Using complementary non-targeted UHPLC-ESI-QTOF-MS and targeted HPLC analyses, we identified over 15,800 spectral features and 150 putative metabolites revealing a marked reorganization of metabolic networks. Principal component, hierarchical clustering, and tanglegram analyses confirmed a deep topological divergence between genotypes, indicating that domestication reprogrammed metabolite associations and reduced overall chemical connectivity. Pathway enrichment analysis showed that the domesticated genotype prioritized primary metabolism particularly lipid, nucleotide, and amino acid biosynthesis while the wild form retained a metabolism dominated by flavonoid, terpenoid, and phenylpropanoid pathways associated with defense, antioxidant activity, and environmental plasticity. Targeted quantification validated these patterns, evidencing a metabolic trade-off between nutritional optimization and stress resilience. Collectively, our results demonstrate that S. edule domestication entailed a functional shift from chemical diversity to energetic efficiency, providing a metabolomic framework to understand how artificial selection reshapes plant secondary metabolism and highlighting the value of wild germplasm for restoring resilience and nutraceutical potential in cultivated species.
Data availability
The datasets generated and analysed during the current study, including mass-to-charge (m/z) features and retention time data obtained under both ionization modes, are provided in the Supplementary Materials (Supplementary Data S1; Tables S1 and S2). Additional data supporting the findings of this study are available from the corresponding author upon reasonable request.
References
Pang, Z. et al. Linking plant secondary metabolites and plant microbiomes: A review. Front. Plant Sci. 12, 621276 (2021).
Sun, Y. & Fernie, A. R. Plant secondary metabolism in a fluctuating world: Climate change perspectives. Trends Plant Sci. 29, 560–571 (2024).
Barrera-Guzmán, L. A., Cadena-Iñiguez, J., Legaria-Solano, J. P. & Sahagún-Castellanos, J. Phylogenetics of the genus Sechium P. Brown: A review. Span. J. Agric. Res. 19, e07R01-e07R01 (2021).
Cadena Iñiguez, J. et al. Biochemical characterization of domesticated varieties of chayote Sechium edule (Jacq.) Sw. fruits compared to wild relatives. Rev. Chapingo Ser. Hortic. 17, 45–55 (2011).
Guzmán, L. Á. B., Solano, J. P. L., Iñiguez, J. C. & Castellanos, J. S. Phylogenetic relationships among Mexican species of the genus Sechium (Cucurbitaceae). Turk. J. Bot. 45, 302–314 (2021).
Aguiñiga-Sánchez, I. et al. Chemical analyses and in vitro and in vivo toxicity of fruit methanol extract of Sechium edule var. nigrum spinosum. Pharm. Biol. 55, 1638–1645 (2017).
Aguiñiga-Sánchez, I. et al. Phytochemical analysis and antioxidant and anti-inflammatory capacity of the extracts of fruits of the Sechium hybrid. Molecules 25, 4637 (2020).
Rivera-Martínez, A. R. et al. Fruit extract of Sechium chinantlense (Lira & F. Chiang) induces apoptosis in the human cervical cancer HeLa cell line. Nutrients 15, 667 (2023).
Cadena-Iñiguez, J. et al. Genotypes of Sechium spp. as a source of natural products with biological activity. Life 15, 15 (2024).
Cadena-Iñiguez, J. et al. The antiproliferative effect of chayote varieties (Sechium edule (Jacq.) Sw.) on tumour cell lines. J. Med. Plant Res 7, 455–460 (2013).
Iñiguez-Luna, M. I. et al. Natural bioactive compounds of Sechium spp. for therapeutic and nutraceutical supplements. Front. Plant Sci. 12, 772389 (2021).
Iñiguez-Luna, M. I. et al. Bioprospecting of Sechium spp. varieties for the selection of characters with pharmacological activity. Sci. Rep. 11, 6185 (2021).
Arista-Ugalde, T. L. et al. Antioxidant and anti-inflammatory effect of the consumption of powdered concentrate of Sechium edule var. nigrum spinosum in Mexican older adults with metabolic syndrome. Antioxidants 11, 1076 (2022).
Cadena-Iñiguez, J. et al. Antiproliferative effect of Sechium edule (Jacq.) Sw., cv. Madre negra extracts on breast cancer in vitro. Separations 9, 230 (2022).
Monroy-Vázquez, M. E. et al. Bio-guided study of an alcoholic extract of Sechium edule (Jacq.) Swartz fruits. Agrociencia 43, 777–790 (2009).
Zeder, M. A. Core questions in domestication research. Proc. Natl. Acad. Sci. U. S. A. 112, 3191–3198 (2015).
Flint-Garcia, S. A. Genetics and consequences of crop domestication. J. Agric. Food Chem. 61, 8267–8276 (2013).
Beleggia, R. et al. Evolutionary metabolomics reveals domestication-associated changes in tetraploid wheat kernels. Mol. Biol. Evol. 33, 1740–1753 (2016).
Ku, Y.-S. et al. The effects of domestication on secondary metabolite composition in legumes. Front. Genet. 11, 581357 (2020).
Dar, M. S. et al. Influence of domestication on specialized metabolic pathways in fruit crops. Planta 253, 61 (2021).
Satrio, R. D., Fendiyanto, M. H. & Miftahudin, M. Molecular dynamics of plant stress and its management 555–607 (Springer, 2024).
Mishra, A. K., Mishra, S., Gupta, S. & Tiwari, S. Decoding plant metabolomics: Integrative insights into metabolic regulation. Theor. Exp. Plant Physiol. 37, 1–26 (2025).
Allwood, J. W. et al. Unravelling plant responses to stress—The importance of targeted and untargeted metabolomics. Metabolites 11, 558 (2021).
Patel, M. K. et al. Plants metabolome study: Emerging tools and techniques. Plants 10, 2409 (2021).
Luna-Ruiz, Jd. J., Nabhan, G. P. & Aguilar-Meléndez, A. Shifts in plant chemical defenses of chile pepper (Capsicum annuum L.) due to domestication in Mesoamerica. Front. Ecol. Evol. 6, 48 (2018).
Shlichta, J. G., Cuny, M. A., Hernandez-Cumplido, J., Traine, J. & Benrey, B. Contrasting consequences of plant domestication for the chemical defenses of leaves and seeds in lima bean plants. Basic Appl. Ecol. 31, 10–20 (2018).
Gaillard, M. D., Glauser, G., Robert, C. A. & Turlings, T. C. Fine‐tuning the ‘plant domestication‐reduced defense’hypothesis: Specialist vs generalist herbivores. New Phytol. 217, 355–366 (2018).
Whitehead, S. R. & Poveda, K. Resource allocation trade-offs and the loss of chemical defences during apple domestication. Ann. Bot. 123, 1029–1041 (2019).
Purugganan, M. D. Evolutionary insights into the nature of plant domestication. Curr. Biol. 29, R705–R714 (2019).
Wink, M. Evolution of secondary plant metabolism. ELS, 1–11 (2016).
Cadena-Zamudio, J. D. et al. Non-Targeted Metabolomic Analysis of Arabidopsis thaliana (L.) Heynh: Metabolic Adaptive Responses to Stress Caused by N Starvation. Metabolites 13, 1021 (2023).
Alseekh, S. et al. Domestication of crop metabolomes: Desired and unintended consequences. Trends Plant Sci. 26, 650–661 (2021).
Klčová, B. et al. Domestication has altered gene expression and secondary metabolites in pea seed coat. Plant J. 118, 2269–2295 (2024).
Wang, C. et al. Differential effects of domesticated and wild Capsicum frutescens L. on microbial community assembly and metabolic functions in rhizosphere soil. Front. Microbiol. 15, 1383526 (2024).
Cervantes-Hernández, F., Ochoa-Alejo, N., Martínez, O. & Ordaz-Ortiz, J. J. Metabolomic analysis identifies differences between wild and domesticated chili pepper fruits during development (Capsicum annuum L.). Front. Plant Sci. 13, 893055 (2022).
Haliński, ŁP. et al. Impact of plant domestication on selected nutrient and anti-nutrient compounds in Solanaceae with edible leaves (Solanum spp.). Genet. Resour. Crop Evol. 66, 89–103 (2019).
Chen, P. et al. Insights into the effect of human civilization on Malus evolution and domestication. Plant Biotechnol. J. 19, 2206–2220 (2021).
Yue, H. et al. Plant domestication shapes rhizosphere microbiome assembly and metabolic functions. Microbiome 11, 70 (2023).
Li, X. et al. Metabolomic analysis reveals domestication-driven reshaping of polyphenolic antioxidants in soybean seeds. Antioxidants 12, 912 (2023).
Gasparini, K., dos Reis Moreira, J., Peres, L. E. P. & Zsögön, A. De novo domestication of wild species to create crops with increased resilience and nutritional value. Curr. Opin. Plant Biol. 60, 102006 (2021).
Singh, J. & van der Knaap, E. Unintended consequences of plant domestication. Plant Cell Physiol. 63, 1573–1583 (2022).
Fernie, A. R., de Vries, S. & de Vries, J. Evolution of plant metabolism: The state-of-the-art. Philos. Trans. R. Soc. Lond. B Biol. Sci. 379, 20230347 (2024).
Dadras, A. et al. Accessible versatility underpins the deep evolution of plant specialized metabolism. Phytochem. Rev. 24, 13–26 (2025).
D’Amelia, V., Docimo, T., Crocoll, C. & Rigano, M. M. Specialized metabolites and valuable molecules in crop and medicinal plants: The evolution of their use and strategies for their production. Genes 12, 936 (2021).
Wang, M., Zhang, S., Li, R. & Zhao, Q. Unraveling the specialized metabolic pathways in medicinal plant genomes: A review. Front. Plant Sci. 15, 1459533 (2024).
Pang, F. et al. PHD-finger family genes in wheat (Triticum aestivum L.): Evolutionary conservatism, functional diversification, and active expression in abiotic stress. Front. Plant Sci. 13, 1016831 (2022).
Krug, A. S., Drummond, B. M. E., Van Tassel, D. L. & Warschefsky, E. J. The next era of crop domestication starts now. Proc. Natl. Acad. Sci. U. S. A. 120, e2205769120 (2023).
Simko, I. Spatio-temporal dynamics of lettuce metabolome: A framework for targeted nutritional quality improvement. Plants 13, 3316 (2024).
Kishor, P. K. et al. Impact of climate change on altered fruit quality with organoleptic, health benefit, and nutritional attributes. J. Agric. Food Chem. 71, 17510–17527 (2023).
Wambugu, P. W. & Henry, R. Supporting in situ conservation of the genetic diversity of crop wild relatives using genomic technologies. Mol. Ecol. 31, 2207–2222 (2022).
Salgotra, R. K. & Chauhan, B. S. Genetic diversity, conservation, and utilization of plant genetic resources. Genes 14, 174 (2023).
Arif, M. & Mukhtar, A. Exploring the role of wild relatives in enhancing genetic diversity, stress tolerance, and resilience of cultivated crops: Innovative breeding strategies, agricultural applications, and future directions for global food security. Agric. Biotechnol. Reflect. 1, 24–37 (2024).
Cadena-Zamudio, J. D., Nicasio-Torres, P., Monribot-Villanueva, J. L., Guerrero-Analco, J. A. & Ibarra-Laclette, E. Integrated analysis of the transcriptome and metabolome of Cecropia obtusifolia: A plant with high chlorogenic acid content traditionally used to treat diabetes mellitus. Int. J. Mol. Sci. 21, 7572. https://doi.org/10.3390/ijms21207572 (2020).
Monribot-Villanueva, J. L. et al. Endorsing and extending the repertory of nutraceutical and antioxidant sources in mangoes during postharvest shelf life. Food Chem. 285, 119–129. https://doi.org/10.1016/j.foodchem.2019.01.136 (2019).
Monribot-Villanueva, J. L. et al. Integrating proteomics and metabolomics approaches to elucidate the ripening process in white Psidium guajava. Food Chem. 367, 130656 (2022).
Rodríguez-Valdovinos, K. Y. et al. Antioxidant and antifungal activities and characterization of phenolic compounds using ultra-high performance liquid chromatography and mass spectrometry (UPLC-MS) of aqueous extracts and fractions from Verbesina sphaerocephala stems. Plants 13, 2791 (2024).
Python Software Foundation. Python Language Reference version 3.8, <https://www.python.org/ > (2020).
Karnovsky, A. & Li, S. Pathway analysis for targeted and untargeted metabolomics. In Computational Methods and Data Analysis for Metabolomics 387–400 (2020).
Lu, Y., Pang, Z. & Xia, J. Comprehensive investigation of pathway enrichment methods for functional interpretation of LC–MS global metabolomics data. Brief. Bioinform. 24, bbac553 (2023).
Leader, D. P., Burgess, K., Creek, D. & Barrett, M. P. Pathos: A web facility that uses metabolic maps to display experimental changes in metabolites identified by mass spectrometry. Rapid Commun. Mass Spectrom. 25, 3422–3426. https://doi.org/10.1002/rcm.5245 (2011).
Kim, S. et al. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res. 49, D1388–D1395. https://doi.org/10.1093/nar/gkaa971 (2020).
Harrington, R. A., Adhikari, V., Rayner, M. & Scarborough, P. Nutrient composition databases in the age of big data: foodDB, a comprehensive, real-time database infrastructure. BMJ Open 9, e026652 (2019).
Kanehisa, M., Furumichi, M., Sato, Y., Matsuura, Y. & Ishiguro-Watanabe, M. KEGG: Biological systems database as a model of the real world. Nucleic Acids Res. 53, D672–D677 (2025).
Kanehisa, M. & Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27–30 (2000).
Chaleckis, R., Meister, I., Zhang, P. & Wheelock, C. E. Challenges, progress and promises of metabolite annotation for LC-MS-based metabolomics. Curr. Opin. Biotechnol. 55, 44–50. https://doi.org/10.1016/j.copbio.2018.07.010 (2019).
Mahieu, N. G. & Patti, G. J. Systems-level annotation of a metabolomics data set reduces 25 000 features to fewer than 1000 unique metabolites. Anal. Chem. 89, 10397–10406 (2017).
Kachman, M. et al. Deep annotation of untargeted LC-MS metabolomics data with Binner. Bioinformatics 36, 1801–1806 (2020).
Cadena-Zamudio, J. D. et al. The use of ecological analytical tools as an unconventional approach for untargeted metabolomics data analysis: the case of Cecropia obtusifolia and its adaptive responses to nitrate starvation.. Funct. Intergr. Genomics 22, 1467–1493 (2022).
cran.r-project. CRAN Packages By Name, <https://cran.r-project.org/web/packages/available_packages_by_name.html> (2020).
Chong, J., Wishart, D. S. & Xia, J. Using MetaboAnalyst 4.0 for comprehensive and integrative metabolomics data analysis. Curr. Protoc. Bioinform. 68, e86. https://doi.org/10.1002/cpbi.86 (2019).
Xia, J., Psychogios, N., Young, N. & Wishart, D. S. MetaboAnalyst: A web server for metabolomic data analysis and interpretation. Nucleic Acids Res. 37, W652-660. https://doi.org/10.1093/nar/gkp356 (2009).
Funding
This work was supported by the Convocatoria 2024–03 for research projects, under project CONV_RGAA_2024_62.
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All authors contributed to the study’s conception and design. The initial idea was presented by Jorge David Cadena-Zamudio and Jorge Cadena-Iñiguez. The design of the experiments and the execution of the experiments were carried out by Samuel David Espinosa-Torres, Rubén San Miguel Chávez, Ramón M. Soto-Hernández and Lucero del Mar Ruiz-Posadas. Data analysis was done by Samuel David Espinosa-Torres, Jorge David Cadena-Zamudio, Ramón M. Soto-Hernández and María Isabel Iñiguez-Luna, edited the manuscript was done by Jorge David Cadena-Zamudio and Ramón M. Soto-Hernández. All authors discussed the results and contributed to the final manuscript.
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Espinosa-Torres, S.D., Cadena-Zamudio, J.D., Soto-Hernández, R.M. et al. Metabolic reprogramming and functional trade-offs during domestication of Sechium edule. Sci Rep (2026). https://doi.org/10.1038/s41598-026-45401-8
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DOI: https://doi.org/10.1038/s41598-026-45401-8
