Cellular instructions for activating genes have remained nearly unchanged across two billion years of evolution, while the mechanisms used to switch genes off vary widely across branches of life, according to a study published in Nature Genetics by the Centre for Genomic Regulation (CRG) in Barcelona. Researchers used a new profiling method called iChIP2 to map chromatin across 12 phylogenetically diverse species, revealing that active gene signatures are nearly identical, but silencing strategies diverge due to ongoing evolutionary conflicts with parasitic DNA.
How Chromatin Regulation Diverged Across the Tree of Life
Inside every cell, DNA wraps around histone proteins. Small chemical tags attached to these proteins act as instructions telling the cell which DNA stretches to read and which to ignore. This system, known as chromatin regulation, enables a single genome to produce diverse cell types like a liver cell or a neuron.
According to the study, the enzymes adding and removing these chemical tags date back roughly two billion years to the Last Eukaryotic Common Ancestor (LECA). Yet, while gene activation signatures remain consistent from humans to sea anemones and soil amoebae, gene silencing mechanisms have continuously evolved.
“The cell’s instructions for activating genes are essentially the same in a human, a sea anemone and a soil amoeba,” says Dr. Arnau Sebé-Pedrós, ICREA Research Professor and senior author of the study. “But the instructions for silencing genes and other genomic elements like transposons have been continuously evolving since our last common eukaryotic ancestor. Different branches of life have developed different molecular toolkits to do the same thing.”
Mapping Genomes With iChIP2 Technology
Until recently, detailed knowledge of chromatin tags came primarily from a handful of laboratory species such as humans, mice, fruit flies, yeast, and the model plant Arabidopsis.
“We wanted to map epigenetic states in scarce cell types in mice and humans,” recalls Dr. Lara-Astiaso, now at the Arc Institute in California. “Eventually, we managed to transform that precursor into a general method for mapping genome regulation across the tree of life – more streamlined, more sensitive, and finally able to handle the particularities of very different species.”
The resulting method, iChIP2, applies unique molecular barcodes to chromatin from multiple species and reads them in a single experiment. The team profiled 12 histone modifications across 12 diverse species, including:
- Amoebozoans (Acanthamoeba castellanii and Dictyostelium discoideum)
- The freshwater amoeba (Naegleria gruberi)
- The marine photosynthetic predator (Bigelowiella natans)
- The alga (Guillardia theta)
- The ciliate (Tetrahymena thermophila)
- Fungi (Spizellomyces punctatus and Saccharomyces cerevisiae)
- The ichthyosporean (Creolimax fragrantissima)
- Plants (Arabidopsis thaliana and Physcomitrium patens)
- The sea anemone (Nematostella vectensis)
“We initially hoped to build a completely universal protocol, but species differ too much for that. Plants and algae have cell walls that require specialised preparation, for example,” says Cristina Navarrete, co-first author of the study. “Once a lab has extracted chromatin from their favourite species, iChIP2 takes over robustly, and from very small amounts of material.”
Did you know? In the soil amoeba Acanthamoeba, a chemical mark that typically signals gene activation in animals has been repurposed by evolution to switch genes off. Different lineages use unique combinations of modifications to keep stretches of DNA silent.
The Evolutionary Conflict With Parasitic DNA
Researchers attribute this vast diversity in gene silencing to an ancient and ongoing conflict between host genomes and parasitic DNA, such as transposable elements (jumping genes) and endogenized viruses. Transposable elements make up roughly half of the human genome and continuously copy and paste themselves into new locations.
Keeping jumping genes silenced is essential for survival. However, these parasitic elements constantly acquire new sequences and fragments of chromatin machinery to evade host detection, forcing hosts to adapt bespoke silencing strategies over hundreds of millions of years.
“If a species loses its repressive mechanisms completely, it can’t tolerate parasitic elements like transposable elements or endogenized viruses. The result is that it’s no longer there. It’s dead,” states Dr. Sebé-Pedrós.
“We’ve established so many new rules from looking at such few species,” notes Dr. Sean Montgomery, one of the study’s authors. “It’s the power of looking at non-model organisms to see how evolution has brought about many differing solutions to the same problems.”
Implications for Comparative Genomics and Medical Research
The findings offer new insights into how genomes evolved on Earth and carry potential implications for medical research investigating human diseases driven by faulty gene regulation, such as cancers. Furthermore, methods like iChIP2 support large-scale international initiatives, including the Earth BioGenome Project and the Wellcome Sanger Institute’s Tree of Life programme, which are rapidly sequencing life on Earth but require functional tools to understand how those genomes are actually utilized.
Frequently Asked Questions
What is chromatin regulation?
Chromatin regulation is the system by which DNA is wrapped around histone proteins and modified with chemical tags, telling the cell which stretches of DNA to read and which to ignore.
How does iChIP2 work?
iChIP2 applies unique molecular barcodes to chromatin extracted from various species, allowing researchers to profile multiple histone modifications across diverse organisms in a single experiment.
Why do gene silencing mechanisms vary across species?
According to researchers, divergent silencing tools evolved as different branches of life adapted to defend against parasitic DNA, such as transposable elements and endogenized viruses.
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