ArticleProceedings of the National Academy of Sciences of the United States of America2016
Convergent evolution of caffeine in plants by co-option of exapted ancestral enzymes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 136 citations in OpenAlex.
- Genomic mechanism of aroma terpenoids biosynthesis in plants.Journal of advanced research · 2026Review
- A case study of evolutionary variability and determinism among type III polyketide synthases.Nature communications · 2026Article
- Conservation of IAMT Preference for Indole Acetic Acid Methylation Across 250 Million Years of Seed Plant Divergence, With Only One Recent Evolutionary Switch in Ocimum.Genome biology and evolution · 2026Article
- Convergence and parallelism in the evolution of plant metabolism.Journal of integrative plant biology · 2026Review
- Plastid 2-oxoglutarate-dependent dioxygenases mediate stereoselective C14β-hydroxylation in cardenolide biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genomic atlas of phytocyanin genes for improvement of climate resilience in bread wheat.BMC plant biology · 2026Article
- Ipecac alkaloid biosynthesis in two evolutionarily distant plants.Nature chemical biology · 2025Article
- Multiple transitions to high l-DOPA 4,5-dioxygenase activity reveal molecular pathways to convergent betalain pigmentation in Caryophyllales.The New phytologist · 2025Article
- Low Caffeine Concentrations Induce Callus and Direct Organogenesis in Tissue Cultures ofPlants (Basel, Switzerland) · 2025Article
- Computational metabolomics reveals overlooked chemodiversity of alkaloid scaffolds in Piper fimbriulatum.The Plant journal : for cell and molecular biology · 2025Article
- Homospermidine synthase evolution and the origin(s) of pyrrolizidine alkaloids in Apocynaceae.American journal of botany · 2025Article
- Yerba mate (eLife · 2025Article
- Anthranilate at the interface of tryptophan and specialized metabolite biosynthesis.Frontiers in plant science · 2025Review
- Convergent evolution of berberine biosynthesis.Science advances · 2024Article
- Evolution of plant metabolism: the state-of-the-art.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Applications of ancestral sequence reconstruction for understanding the evolution of plant specialized metabolism.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Evolution of the biochemistry underpinning purine alkaloid metabolism in plants.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Two ubiquitous aldo-keto reductases in the genus Papaver support a patchwork model for morphine pathway evolution.Communications biology · 2024Article
- The evolutionary origin of naturally occurring intermolecular Diels-Alderases from Morus alba.Nature communications · 2024Article
- Greening up organic reactions with caffeine: applications, recent developments, and future directions.RSC advances · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Convergent evolution is a process that has occurred throughout the tree of life, but the historical genetic and biochemical context promoting the repeated independent origins of a trait is rarely understood. The well-known stimulant caffeine, and its xanthine alkaloid precursors, has evolved multiple times in flowering plant history for various roles in plant defense and pollination. We have shown that convergent caffeine production, surprisingly, has evolved by two previously unknown biochemical pathways in chocolate, citrus, and guaraná plants using either caffeine synthase- or xanthine methyltransferase-like enzymes. However, the pathway and enzyme lineage used by any given plant species is not predictable from phylogenetic relatedness alone. Ancestral sequence resurrection reveals that this convergence was facilitated by co-option of genes maintained over 100 million y for alternative biochemical roles. The ancient enzymes of the Citrus lineage were exapted for reactions currently used for various steps of caffeine biosynthesis and required very few mutations to acquire modern-day enzymatic characteristics, allowing for the evolution of a complete pathway. Future studies aimed at manipulating caffeine content of plants will require the use of different approaches given the metabolic and genetic diversity revealed by this study.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.