CRISPR-modified ants go "space cadet" without a sense of smell

CRISPR-modified ants go "space...
Ants detect pheromones though porous hairs on their antennae
Ants detect pheromones though porous hairs on their antennae
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Three mutant ants in a colony were engineered to lack a gene that enables their “sense of smell”
Three mutant ants in a colony were engineered to lack a gene that enables their “sense of smell”
Ants detect pheromones though porous hairs on their antennae
Ants detect pheromones though porous hairs on their antennae

If a human being loses the sense of smell, it's a massive inconvenience. But in ants, it's a crippling handicap that prevents them from participating in ant society. A pair of independent studies from two teams used CRISPR technology to genetically alter ants to remove their ability to "smell," which resulted in their inability to interact with normal ants and produced changes in their brains.

Ants live in societies that are so organized that they are the go-to metaphor for political regimentation. This organization is so strong that ant colonies are often described as a superorganism, with individual ants being little more than subunits of a much larger, more complex organism.

This not only makes ants a fascinating topic of study in themselves, but also provides a way of learning more about genetics. This is because altering the genes of ants can result in changes in complex behavior inside the colony. This is especially true if those genes affect the ability of ants to detect pheromones through their antennae – what in mammals would be called a sense of smell.

Pheromones are the glue that hold ant society together. These chemicals allow ants to recognize one another, to detect intruders, mark out trails, determine one another's status, and send instructions to tell ants where to go and what to do. This means that if you alter the genes affecting pheromone receptors, the effects will be very obvious.

Another advantage of working with ants is that all the ants in a colony are very closely related and some species of ants can actually be induced to reproduce by parthenogenesis to create a colony of clones. This was the case in the study by a team from The Rockefeller University that used clonal raider ants (Ooceraea biroi) that don't have queens in their colonies and single, unfertilized eggs develop as clones.

Previous research had discovered that even though ants have 350 genes for odorant receptors, all of these are associated with a single co-receptor. This means that to eliminate an ant's sense of smell, it isn't necessary to eliminate the 350 receptors, but just the single Orco co-receptor. This was done using CRISPR technology, which is a recent genetic engineering technique based on a defense mechanism used by bacteria to sample the DNA of attacking viruses so they can identify future attacks and fend them off.

Three mutant ants in a colony were engineered to lack a gene that enables their “sense of smell”
Three mutant ants in a colony were engineered to lack a gene that enables their “sense of smell”

By cutting out a group of odorant receptor genes called 9-exon-alpha OR that produces a protein called Orco, the Rockefeller team was able to prevent a powerful set of pheromones called hydrocarbons from being detected. The altered larvae were carefully grown, then introduced into the colony to prevent the other worker ants from rejecting them. Each ant was color coded to make them easy to identify by an automated imaging system.

Not surprisingly, the modified ants had trouble fitting in with the normal ones, being unable to handle even simple tasks, like following a pheromone trail. But what was not expected was that removing the smell receptors also altered the brains of the ants. Many insects, including mosquitoes, fruit flies, and moths, have their brains hardwired to sense odors, but ant brains turn out to be more like mammals, which only produce the proper structures for smell through use. In the modified ants, the structure called a glomerulus failed to develop properly.

In another study conducted by researchers at researchers at New York University and the NYU School of Medicine, Arizona State University, the University of Pennsylvania, and Vanderbilt University, three ants from a colony of Indian jumping ant (Harpegnathos saltater) were altered in the same manner as in the Rockefeller study. The jumping ant was used because this is a species where, if the queen is removed, workers can be induced to become pseudo-queens that lay eggs, allowing for genetically identical ants to be produced.

As in the Rockefeller study, the modified ants exhibited social problems. In this case, they exhibited a behavior one researcher called "space cadet," where the ants failed to interact with other ants, wandered out of the nest, couldn't forage for food, and didn't groom males in the pre-mating ritual. In addition, unlike other females, the modified ants wouldn't engage in antenna duels for dominance after the queen was removed.

Another effect was that, as in the Rockefeller study, the brains of the mutants were similarly affected with the lack of glomerulus development.

"These studies are proof of principle that you can do genetics in ants," says Daniel Kronauer, an assistant professor at The Rockefeller University. "If you're interested in studying social behaviors and their genetic basis, ants are a good system. Now, we can knock out any gene that we think will influence social behavior and see its effects."

"Better understanding, biochemically speaking, how behavior is shaped could reveal insights into disorders in which changes in social communication are a hallmark, such as schizophrenia or depression," added Shelley Berger, the Daniel S. Och University Professor at the University of Pennsylvania.

The research was published in Cell [1] [2].

Sources: The Rockefeller University, NYU

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