A deep-time landscape of plant cis-regulatory sequence evolution.
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| Title: | A deep-time landscape of plant cis-regulatory sequence evolution. |
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| Authors: | Amundson, Kirk R. (AUTHOR), Hendelman, Anat (AUTHOR), Ciren, Danielle (AUTHOR), Yang, Hailong (AUTHOR), de Neve, Amber E. (AUTHOR), Tal, Shai (AUTHOR), Sulema, Adar (AUTHOR), Jackson, David (AUTHOR), Bartlett, Madelaine E. (AUTHOR), Lippman, Zachary B. (AUTHOR), Efroni, Idan (AUTHOR) |
| Source: | Science. 5/21/2026, Vol. 392 Issue 6800, p1-16. 16p. |
| Subjects: | Cis-regulatory elements (Genetics), Conserved sequences (Genetics), Comparative genomics, Plant genomes, Developmental biology, Molecular phylogeny, Genetic regulation, Genomes |
| Abstract: | Developmental gene function is often conserved over deep time, but cis-regulatory sequence conservation is difficult to identify. Rapid sequence turnover, paleopolyploidy, structural variation, and limited phylogenomic sampling have impeded conserved noncoding sequence (CNS) discovery. Using Conservatory, an algorithm that leverages microsynteny and iterative alignments to map CNS-gene associations over evolution, we uncovered ~2.3 million CNSs, including more than 3000 predating angiosperms, from 284 plant species spanning 300 million years of diversification. Ancient CNSs were enriched near developmental regulators, and mutating CNSs near HOMEOBOX genes produced strong phenotypes. Tracing CNS evolution uncovered key principles: CNS spacing varies, but order is conserved; genomic rearrangements form new CNS-gene associations; and ancient CNSs are preferentially retained among paralogs but are often lost as cohorts or evolve into lineage-specific CNSs. Editor's summary: Plant genomes have complicated histories shaped by varying polyploidies, large fractions being composed of transposons, and whole-genome duplications. These features confound many modern genome alignment tools that were developed for use in animals, complicating the search for conserved sequences. Amundson et al. created and implemented an algorithm to first identify orthologous genes among deeply diverged plants and short, conserved nongenic sequences in nearby regions that may act as enhancers. Most of these sequences contained transcription factor–binding sites or other features denoting regulatory potential, and the disruption of several in tomato resulted in deleterious developmental effects. —Corinne Simonti INTRODUCTION: Defining the principles that govern cis-regulatory sequence conservation and divergence is key to deciphering the genetic basis of phenotypic evolution. However, identifying cis-regulatory elements across organismal diversity is often challenging, especially over deep time. Such challenges are amplified in plant genomes, where rapid sequence evolution, repeated cycles of whole-genome and local gene duplication, fractionation, and lineage-specific gene retention and loss obscure orthology relationships. These complex dynamics of genome evolution are poorly accommodated by existing whole-genome alignment tools, necessitating the development of new approaches. RATIONALE: To overcome these limitations, we developed Conservatory, a comparative genomics framework for identifying conserved noncoding sequences (CNSs). Conservatory uses homolog groups as anchors, performs synteny-based local alignments within windows of ~120 kb, and progressively propagates alignments across a phylogeny. This gradual, phylogeny-aware approach allows detection of short conserved segments that would be missed by direct pairwise comparisons, while preserving a record of CNS-gene relationships across lineage-specific duplications. RESULTS: Applying Conservatory to 284 plant species spanning ~300 million years of diversification identified ~2.3 million CNSs. CNSs were enriched for regulatory chromatin features and found near the centers of open chromatin, indicating that these are bona fide regulatory sequences. Conservation depth varied widely, but 3954 CNSs predated angiosperm diversification, and 633 were shared between gymnosperms and angiosperms. These ancient elements were enriched near developmental regulators and transcription factors. Disruption of CNSs near conserved homeobox genes resulted in pronounced phenotypes, demonstrating the functionality of these elements. Tracing CNS histories revealed general principles of regulatory evolution in complex genomes. Plant CNSs were highly enriched near transcription start and stop sites, although about a quarter were located more than 25 kb away from their associated genes. These distal CNSs were significantly associated with chromatin loops. CNS spacing and distances changed through evolution, but their relative order was often conserved. Gene duplication is common in plants. By tracking paralog divergence, we show that genes are often duplicated along with their cis-regulatory regions, which diverge to form paralog-specific CNSs. However, even ancient duplications retain some original CNSs, suggesting that functional redundancy may persist even among highly diverged paralogs. A broad, time-resolved analysis of CNS evolution shows that CNS divergence and loss is punctuated and lineage-specific, with grasses being an extreme example. CONCLUSION: Cis-regulatory conservation in plants has traditionally been seen as rare beyond closely related species within genera and families. Our findings challenge this view, showing that a deeply conserved regulatory code exists and is widespread in plants but has been hidden by the extreme evolutionary dynamics of plant genomes. Conservatory provides a map of CNSs across deep time and offers a framework for identifying patterns and principles that govern gene regulation and its evolution. This knowledge can be used to study phenotypic evolution through cis-regulatory changes, can be applied for targeted cis-regulatory engineering, and may be relevant to other eukaryotic clades undergoing rapid genome evolution. Identification of deeply conserved noncoding sequences in plants.: The Conservatory algorithm identifies deeply conserved elements in plants despite their rapid genome evolution. Tracing the evolution of these elements shows that they are mobile but conserve order, are often duplicated together with their associated genes, and diverge to form lineage-specific variants. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Developmental gene function is often conserved over deep time, but cis-regulatory sequence conservation is difficult to identify. Rapid sequence turnover, paleopolyploidy, structural variation, and limited phylogenomic sampling have impeded conserved noncoding sequence (CNS) discovery. Using Conservatory, an algorithm that leverages microsynteny and iterative alignments to map CNS-gene associations over evolution, we uncovered ~2.3 million CNSs, including more than 3000 predating angiosperms, from 284 plant species spanning 300 million years of diversification. Ancient CNSs were enriched near developmental regulators, and mutating CNSs near HOMEOBOX genes produced strong phenotypes. Tracing CNS evolution uncovered key principles: CNS spacing varies, but order is conserved; genomic rearrangements form new CNS-gene associations; and ancient CNSs are preferentially retained among paralogs but are often lost as cohorts or evolve into lineage-specific CNSs. Editor's summary: Plant genomes have complicated histories shaped by varying polyploidies, large fractions being composed of transposons, and whole-genome duplications. These features confound many modern genome alignment tools that were developed for use in animals, complicating the search for conserved sequences. Amundson et al. created and implemented an algorithm to first identify orthologous genes among deeply diverged plants and short, conserved nongenic sequences in nearby regions that may act as enhancers. Most of these sequences contained transcription factor–binding sites or other features denoting regulatory potential, and the disruption of several in tomato resulted in deleterious developmental effects. —Corinne Simonti INTRODUCTION: Defining the principles that govern cis-regulatory sequence conservation and divergence is key to deciphering the genetic basis of phenotypic evolution. However, identifying cis-regulatory elements across organismal diversity is often challenging, especially over deep time. Such challenges are amplified in plant genomes, where rapid sequence evolution, repeated cycles of whole-genome and local gene duplication, fractionation, and lineage-specific gene retention and loss obscure orthology relationships. These complex dynamics of genome evolution are poorly accommodated by existing whole-genome alignment tools, necessitating the development of new approaches. RATIONALE: To overcome these limitations, we developed Conservatory, a comparative genomics framework for identifying conserved noncoding sequences (CNSs). Conservatory uses homolog groups as anchors, performs synteny-based local alignments within windows of ~120 kb, and progressively propagates alignments across a phylogeny. This gradual, phylogeny-aware approach allows detection of short conserved segments that would be missed by direct pairwise comparisons, while preserving a record of CNS-gene relationships across lineage-specific duplications. RESULTS: Applying Conservatory to 284 plant species spanning ~300 million years of diversification identified ~2.3 million CNSs. CNSs were enriched for regulatory chromatin features and found near the centers of open chromatin, indicating that these are bona fide regulatory sequences. Conservation depth varied widely, but 3954 CNSs predated angiosperm diversification, and 633 were shared between gymnosperms and angiosperms. These ancient elements were enriched near developmental regulators and transcription factors. Disruption of CNSs near conserved homeobox genes resulted in pronounced phenotypes, demonstrating the functionality of these elements. Tracing CNS histories revealed general principles of regulatory evolution in complex genomes. Plant CNSs were highly enriched near transcription start and stop sites, although about a quarter were located more than 25 kb away from their associated genes. These distal CNSs were significantly associated with chromatin loops. CNS spacing and distances changed through evolution, but their relative order was often conserved. Gene duplication is common in plants. By tracking paralog divergence, we show that genes are often duplicated along with their cis-regulatory regions, which diverge to form paralog-specific CNSs. However, even ancient duplications retain some original CNSs, suggesting that functional redundancy may persist even among highly diverged paralogs. A broad, time-resolved analysis of CNS evolution shows that CNS divergence and loss is punctuated and lineage-specific, with grasses being an extreme example. CONCLUSION: Cis-regulatory conservation in plants has traditionally been seen as rare beyond closely related species within genera and families. Our findings challenge this view, showing that a deeply conserved regulatory code exists and is widespread in plants but has been hidden by the extreme evolutionary dynamics of plant genomes. Conservatory provides a map of CNSs across deep time and offers a framework for identifying patterns and principles that govern gene regulation and its evolution. This knowledge can be used to study phenotypic evolution through cis-regulatory changes, can be applied for targeted cis-regulatory engineering, and may be relevant to other eukaryotic clades undergoing rapid genome evolution. Identification of deeply conserved noncoding sequences in plants.: The Conservatory algorithm identifies deeply conserved elements in plants despite their rapid genome evolution. Tracing the evolution of these elements shows that they are mobile but conserve order, are often duplicated together with their associated genes, and diverge to form lineage-specific variants. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.adt8983 |
