Research led by Mia Levine shows how a vital DNA protection protein complex adapts to new threats without compromising its essential functions.
3 min. read
Biologist Mia Levine and colleagues have demonstrated how a pair of essential protein partners undergo rapid evolutionary change to counter fast-evolving parasitic DNA while maintaining core cellular functions. The work presents novel insight into how evolution works at the molecular level.
(Image: Getty images/Joao Paulo Burini)
Key Takeaways
Essential proteins can lead double lives: even while safeguarding ancient cellular functions like telomere protection, some must continually reinvent themselves to counter fast-moving threats from “selfish” DNA.
Two key members of the telomere end-protection complex, HipHop and HOAP, evolve rapidly but remain indispensable, revealing how coordinated protein coevolution preserves a system that can’t afford to fail.
Swapping these proteins between closely related fly species shows just how tightly tuned this partnership is, as a handful of amino acids makes the difference between catastrophic chromosome fusion and a fully functional, threat-resilient genome.
In Lewis Carroll’s “Through the Looking-Glass,” Alice is stuck in a never-ending race with the Red Queen yet never gains a lead. “It takes all the running you can do to keep in the same place,” the Queen says.
“Though we typically use this metaphor to describe evolutionary arms races between hosts and parasites or hosts and pathogens, the ‘Red Queen Hypothesis’ also characterizes the ongoing battles within our genome,” says Mia Levine, a biologist at the University of Pennsylvania.
Some stretches of DNA are “selfish,” she explains. Mobile genetic elements, for example, have evolved the ability to move around the genome, cutting or copying and then pasting themselves in new locations, sometimes disrupting genes or other important functional DNA stretches. To keep these “bad guys” in check, cells have evolved molecular defenses that detect, silence, or physically block them.
But this battleground presents a fundamental puzzle that has long vexed scientists: How do life’s most essential, stable functions depend on proteins that must also constantly undergo rapid changes to fend off foes?
Now, Levine and colleagues have demonstrated how a pair of essential protein partners navigate this challenge. The team focused on the genes in Drosophila melanogaster, fruit flies, that are responsible for creating the protective caps—telomeres—at the ends of chromosomes, which Levine likens to the plastic tips on shoelaces.
The findings, published in Science, show that while the function of these proteins—protecting the end of chromosomes—remains constant, the proteins themselves are constantly shapeshifting to fight off selfish elements.
To prevent chromosome tips from fusing—which can cause genetic instability, fertility issues, and cell and organismal death—a group of six proteins assemble into the end-protection complex to bind telomeric DNA.
The researchers found that two members of this complex, the HipHop protein and its binding partner HOAP, evolve far faster than the other subunits yet are indispensable for telomere protection.
“We offer a first glimpse of the fascinating biology faithfully preserved by an essential multiprotein complex whose subunits are under potent evolutionary pressure to change,” says Levine.
They tested whether these proteins have to evolve in lockstep (coevolve) to keep the complex intact by using gene editing tools to replace the native HipHop in D. melanogaster flies with the version from another closely-related fly species, D. yakuba.
The researchers found that that when they engineered D. melanogaster flies to make the D. yakuba version of HipHop instead of their own version, the flies died—their cells showed rampant end-to-end chromosome fusions.
Conversely, reverting just six adaptively evolving amino acids—the building blocks of proteins—in D. yakuba HipHop back to their D. melanogaster counterparts, or introducing the D. yakuba version of HOAP, restored protein recruitment, telomere protection, and viability.
As HOAP evolves to silence internal enemies, Levine explains, the HipHop protein is forced to evolve in tandem.
How selfish DNA “antagonizes” these proteins is largely unknown, says Levine. “But similar evolutionary signatures in primates suggest this kind of compensatory evolution may be widespread and studying it could clarify how genomes retain ancient functions while adapting to ever-shifting threats.”
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