Modern approaches to study plant–insect interactions in chemical ecology


Phytochemical variation among plant species is one of the most fascinating and perplexing features of the natural world and has implications for both human health and the functioning of ecosystems. A key area of research on phytochemical variation has focused on insects that feed on plants and the enormous diversity of plant-derived compounds that reduce or deter damage by insects. Empirical studies on the ecology and evolution of these chemically mediated plant–insect interactions have been guided by a long history of theoretical development. However, until recently, such theory was substantially limited by inadequate data, a situation that is rapidly changing as ecologists partner with chemists utilizing the latest technological advances. In this Review, we aim to facilitate the union of ecological theory with modern chemistry by discussing important theoretical frameworks for studying chemical ecology and outlining the steps by which hypotheses on insect–phytochemical interactions can be advanced using current methodologies and statistical approaches. We highlight unique approaches to isolation, synthesis, spectroscopy, metabolomics and genomics relevant to chemical ecology and describe future areas for research that will bring an unprecedented understanding of phytochemical variation.

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Fig. 1
Fig. 2: Crude 1H NMR spectra from leaves of two Piper species.
Fig. 3: Periplanone and mandelalide A structure determination by total synthesis.
Fig. 4: Syntheses of methyl jasmonate and proposed modifications for asymmetric synthesis.
Fig. 5: Early approaches to the biomimetic synthesis of natural products.
Fig. 6: Building diversity via biosynthesis and diversity-oriented synthesis.


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The authors dedicate this article to Professor Jerrold Meinwald for his transformative contributions to the field of chemical ecology. The authors thank M.A. Stanton and two anonymous reviewers for their excellent edits and suggestions to this manuscript. The authors’ research was funded by the National Science Foundation (DEB-1442103 and DEB-1638793), the FAPESP (São Paulo Research Foundation, 2014/50316-7) and by a generous donation from the Hitchcock Fund for Chemical Ecology Research.

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L.A.D., C.S.P., K.M.O., L.A.R., T.J.M., A.M.S., M.L.F., T.L.P., L.M.G., P.J.H., A.E.E., A.E.G., J.G.H., C.M., S.Y., N.A.P., N.D.M., J.P.J., H.L.S., O.S. and C.S.J. researched the data for the article and wrote the article. All authors contributed to discussion of the content and reviewed and/or edited the manuscript before revision.

Correspondence to Christopher S. Jeffrey.

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Plant secondary metabolites

Organic compounds not associated with primary metabolic functions; in plants in particular, these compounds have been the subject of research in biomedical fields and in chemical ecology, in which they have been found to have largely defensive functions (for example, anti-herbivore and antibacterial functions).


The evolution of reciprocal adaptation in response to reciprocal natural selection occurring with respect to a pair or complex of interacting species; often hypothesized to be associated with adaptive radiation and co-diversification.


Combined effects of compounds in a mixture that are greater than the sum of effects for the individual compounds acting in isolation.


The evolutionary process that results in the formation of new species by the divergence of an ancestral population into two genetically independent populations. This process is most often characterized by the evolution of reproductive isolation and the subsequent independent evolution of lineages.


Organisms characterized by a unique form of parasitic lifestyle, in which the host is killed by the developing juvenile stage; the most diverse taxa, the wasps (insect order Hymenoptera) and flies (insect order Diptera), have a dramatic influence on the ecology of terrestrial ecosystems.

Antagonistic pleiotropy

A type of genetic architecture in which a single genetic locus affects more than one trait (which can include performance or fitness in more than one environment), with effects of one trait (or in one environment) being positive and effects of the other trait (or environment) being negative.

Dereplication methods

Fast identification of compounds using orthogonal physicochemical characteristics to compare spectroscopic data with molecular features gleaned from libraries of known compounds and to confirm identifications.


Phytochemicals that have antibacterial or antifungal properties.

Next-generation sequencing

Modern DNA sequencing platforms that leverage direct sequencing by synthesis technologies to simultaneously determine the DNA sequences of millions or hundreds of millions of DNA fragments. Also known as high-throughput or massively parallel sequencing, these methods have revolutionized genomics.

RNA sequencing

The use of next-generation DNA sequencing approaches to characterize and quantify RNA from biological samples. RNA extracted from tissue is converted into cDNA and directly sequenced on next-generation sequencing platforms such as Illumina. These approaches allow for efficient characterization of the coding regions of genomes (for example, transcriptome sequencing) and for analysis of differential gene expression.

Genome-wide association studies

Observational studies of a genome-wide set of genetic variants in a sample of phenotypically variable individuals aimed at detecting specific variants in which genotypic variation is associated with phenotypic variation.

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Dyer, L.A., Philbin, C.S., Ochsenrider, K.M. et al. Modern approaches to study plant–insect interactions in chemical ecology. Nat Rev Chem 2, 50–64 (2018).

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