How an ant’s nose knows

(Press-News.org) Ant societies are built on scent. Pheromones guide the insects to food, warn them of predators, and regulate the rhythms of their colonies. This chemical communication system is governed by a simple rule: one receptor, one neuron. Ant genomes contain hundreds of odorant receptor genes, each encoding a receptor tuned to specific chemicals. Were a neuron to express multiple receptors at once, the messages arriving in the brain would be scrambled, and the ant would lose its finely tuned sense of smell.

Now, scientists working with the clonal raider ant have discovered the unique process by which each neuron selects a single odorant receptor from a vast library of genes. The findings, published in Current Biology, settle the longstanding mystery of how ants keep sensory signals clear.

"We're describing a new form of gene regulation," says Daniel Kronauer, head of the Laboratory of Social Evolution and Behavior at Rockefeller. "Our results demonstrate the importance of studying less conventional model species. We were able to discover new, fundamental molecular phenomena in clonal raider ants that we could not have seen in fruit flies."

One receptor, one neuron

A central principle of smell is that every neuron must have its own molecular identity. "It's a kind of dogma in the field of sensory neuroscience," says Giacomo Glotzer, a graduate student in the Kronauer lab. "Each sensory neuron typically expresses one receptor—and that gives it its identity."

Different species solve the "one receptor, one neuron" puzzle in different ways. Fruit flies rely on molecular switches that turn individual genes on or off, ensuring that only one receptor emerges from each sensory neuron. Mammals employ a more chaotic approach, with each neuron randomly reshuffling its chromatin until only one receptor gene remains accessible.

It was unknown, however, whether ants employed a strategy more like the fly or the mouse, or altogether different strategy. Unlike fruit flies, which get by with about 60 odorant receptors, ants have several hundred—comparable in scale to that of mammals. And many of their receptors are packed into clusters of nearly identical genes. In such a crowded neighborhood, turning on one gene might incidentally activate others. A simple strategy like the fruit fly’s may not work for the ant’s complex sense of smell, suggesting that ants maintain the 1:1 olfactory ratio some other way.

Building on a foundational paper on the subject that the team had published in 2023, the lab set out to capture this elusive mechanism in action. After dissecting the antennal tissue of clonal raider ants, the team then used RNA sequencing, to determine which genes were turned on, and RNA fluorescence in situ hybridization, to localize those genes in the ant antenna. They then used numerous cutting-edge molecular and computational techniques to create a clear image of one chosen receptor surrounded by its quieted neighbors.

They found that, when an ant neuron switches on its chosen receptor gene, it doesn't stop there. The RNA polymerase—the engine that copies the DNA into RNA—continues past that gene's normal endpoint, spilling into the genes that sit downstream of the target. These "readthrough" transcripts remain trapped in the nucleus, likely because they lack the unique tag required for export. The authors speculate that these transcripts are non-functional, but that their production itself is what silences downstream genes. Meanwhile, the neuron also generates "antisense" RNAs in the other direction. The polymerase here acts as a roadblock to silence upstream genes that might otherwise have turned on.

The result is a protective genetic shield around the chosen receptor gene.

"When we took the mechanism apart and dissected it into its constituent parts, we found that this strategy serves to silence the local genomic environment, giving that cell its singular receptor identity," says Parviz Daniel Hejazi Pastor, a biomedical fellow in the Kronauer lab. "Our findings center around transcriptional interference—that the neuron chooses one receptor by preventing the true transcription of other receptors both upstream and downstream."

Beyond clonal raider ants

The team went on to confirm that this same mechanism is at work in other social insects, including the Indian jumping ant and the honeybee. These findings raise the possibility that many insects, both social and non-social, use transcriptional interference to maintain a 1:1 ratio between receptors and neurons. "This mechanism may be even more broadly distributed than we thought, particularly among insect species with large repertoires of olfactory receptor genes" Kronauer says. "It's even possible that fruit flies are the odd ones out."

The implications extend far beyond insect olfaction. By showing that tight clusters of related genes can be governed by two-way safeguards—readthrough that quiets downstream neighbors and antisense transcription that blocks upstream ones—this work offers a blueprint for how genomes might keep large gene families in check. The results also point to a potential mechanism for explaining how ants quickly expand their sense of smell over relatively short evolutionary time. The findings described in this paper might allow newly duplicated receptor genes to be integrated into a sensory system without the need to coevolve additional regulatory mechanisms.

"Once you have the system in place like this, you can allow it to become more complex without disrupting anything," Kronauer says. "We speculate that this kind of gene regulatory system contributes to allowing the ants to evolve new olfactory receptors so quickly."

END