Hiding in plain sight: Scientists uncover the ancient DNA sequences that control gene function across plant evolution
A ground-breaking study has traced thousands of conserved regulatory elements back 300 million years, revealing deep principles of plant genome evolution – a discovery that could pave the way for more precise engineering of crop traits.
Rapid advances in plant genomics and genome editing are transforming the possibilities for improving crop traits in the face of growing environmental, disease and yield pressures.
The key challenge is no longer whether plants can be engineered to meet human needs, but which genomic sequences we should target to achieve predictable and beneficial results.
In a new study published online by the journal Science, an international collaboration of plant scientists has uncovered a vast and previously hidden trove of ancient regulatory DNA sequences that have helped control plant development for hundreds of millions of years.
Although ancient regulatory DNA sequences are well-studied in animal genomes, they were long thought to be rare or absent in plants.
Genetic sequences in plants frequently duplicate and rearrange themselves, which masks their evolutionary history.
Professor Madelaine Bartlett, a research group leader at the University of Cambridge’s Sainsbury Laboratory who co-led the study, said: “Plant genes are continually shuffling themselves around, which makes the links between genes and their regulators extremely hard to spot. Repeated duplication of entire genomes, followed by gene loss and rearrangement, hide relationships between genes and their regulators from us. As a result, most known plant cis-regulatory sequences were thought to be young, in evolutionary terms.”
To solve this long-standing challenge, the scientists built a new computational platform, Conservatory, that uses plant genetic data generated by the global plant research community to detect conserved regulatory DNA.
By analysing 284 plant species, this study has now identified ~2.3 million conserved non-coding sequences (CNSs), creating a rich, publicly available resource to help scientists understand how gene regulation evolves across plant lineages.
Given the power of regulatory sequence evolution to shape form, pinpointing the sequences that have stood the test of evolutionary time opens the door to directed, precise engineering of plant traits for increased productivity and resilience.
The findings reveal that ancient regulatory sequences can be maintained, despite the repeated genome duplications and extensive genetic reshuffling common in plant genomes.
This work raises the enticing possibility that similar ancient regulatory sequences may be uncovered in other plant species’ lineages where genome evolution is similarly complex.
The Conservatory Project, spearheaded by the labs of Madelaine Bartlett (Sainsbury Laboratory Cambridge University), Idan Efroni (The Hebrew University of Jerusalem), and Zachary Lippman (Cold Spring Harbor) identified more than 2 million conserved non-coding sequences (CNSs) across green plant diversity through the mammoth efforts of co-first co-authors Kirk R. Amundson from University of Massachusetts Amherst and Anat Hendelman from Cold Spring Harbor Laboratory.
Many of these regulatory elements pre-date the emergence of flowering plants, with some extending back 300 million years.
“These sequences have been hiding in plain sight,” said Professor Efroniwho designed the new gene-centric algorithm Conservatory. “Plant genomes are extraordinarily complex and that complexity has made it very difficult to trace regulatory DNA far back in time. What we show here is that deeply conserved regulatory programmes do exist and they are, in fact, widespread.”
Phylogeny of the 284 species of plants included in Conservatory data set. Conservatory uncovered ~2.3 million conserved non-coding DNA sequences across 284 plant species from 72 families including eudicots, monocots, gymnosperms, and algae. Illustrations by Professor Madelaine Bartlett.
Cracking a long-standing challenge in plant genomics
Cis-regulatory elements are short stretches of non-coding DNA that control when and where genes are switched on. They are powerful drivers of morphological evolution.
However, in plants their evolutionary history has remained poorly understood. Scientists know that many developmental genes perform similar roles across species, however, their regulatory regions often appear weakly conserved.
The Conservatory Project approach combines microsynteny, gradual alignments and deep phylogenomic sampling to detect conserved regulatory DNA even when sequences are substantially diverged.
“Conservatory was able to capture sequence conservation across deep time, while accounting for gene duplication and rapid divergence,” said Professor Lippman. “This allowed us to bridge alignment gaps that were previously impossible to cross.”
Ancient regulators of development
The study found that deeply conserved CNSs are strongly enriched near genes that control plant development, including key transcription factors. Disrupting these sequences can lead to severe developmental defects, underscoring their functional importance.
To determine the functional roles of deeply conserved CNS-gene associations, they focused on genes with canonical roles in embryogenesis. The researchers then asked whether ancient CNSs also underlie other development processes.
They analysed known cis-regulatory elements controlling eight transcription factors involved in meristem, leaf, flower, and epidermal development. In every case the functional regulatory elements overlapped with ancient CNSs identified by Conservatory.
One of the most striking examples was found in the promoter WUSCHEL, which is a core regulator of stem cell maintenance. Elements within this promoter have been conserved for 300 million years. While their precises positions have shifted over time, their relative order has been maintained, revealing a surprising mix of stability and flexibility.
“These sequences are not frozen relics,” said first co-author Dr Amundson. “They can move, duplicate and diversify, yet still preserve the regulatory logic required for development.”
Rethinking how genes are regulated
The research also challenges assumptions about where regulatory elements are located.
Around 25% of CNSs were found to be more than 25 kilobases away from the genes they regulate, sometimes bypassing neighbouring genes entirely.
“This suggests that traditional reporter constructs may miss critical regulatory regions,” said first co-author Dr Hendelman. “It raises important questions about how gene regulation is experimentally studied in plants. Are we missing real expression patterns?”
Further analysis showed that new regulatory sequences often arise following gene duplication.
In many cases, duplicated genes diverge asymmetrically: one copy retains ancestral regulatory elements, while the other acquires novel ones. Some plant lineages, including grasses (Poaceae) experienced particularly dramatic regulatory divergence early in their evolution. This dramatic regulatory rewiring may underpin the evolution of plant form, an area ripe for future discovery.
The Conservatory data set for 284 plant species is available at http://conservatorycns.com
Reference
Kirk R. Amundson, Anat Hendelman, Danielle Ciren, Hailong Yang, Amber E. de Neve, Shai Tal, Adar Sulema, David Jackson, Madelaine E. Bartlett, Zachary B. Lippman, Idan Efroni (2025) A deep-time landscape of plant cis-regulatory sequence evolution. Science DOI: 10.1126/science.adt8983
Funding
This research was supported by the United States-Israel Binational Science Foundation, Israel Science Foundation, Howard Hughes Medical Institute, U.S. National Science Foundation, USDA AFRI and The Gatsby Charitable Foundation.