Genes Help Decide When It’s Time to Look for New Food

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March 16, 2011

Genes Help Decide When It’s Time to Look for New Food

A worm deciding whether to leave its food.

For worms, choosing when to search for a new dinner spot depends on many

factors, both internal and external: how hungry they are, for example, how much

oxygen is in the air, and how many other worms are around. A new study

demonstrates this all-important decision is also influenced by the worm's

genetic make-up.

In the simple Caenorhabditis elegans nematode, the researchers found that

natural variations in several genes influence how quickly a worm will leave a

lawn of bacteria on which it's feeding. One of the genes, called tyra-3,

produces a receptor activated by adrenaline—a chemical messenger involved in the

'fight-or-flight' response. The findings appeared online March 16, 2011, in the

journal Nature.

" What's encouraging to us about this story is that molecules related to

adrenaline are implicated in arousal systems and in decision-making across a lot

of different animals, including humans, " says Medical Institute

investigator Cornelia Bargmann of Rockefeller University in New York, who

mentored the work of graduate student Andres Bendesky. These parallels between

diverse species suggest that aspects of our decision-making abilities have

ancient evolutionary roots.

“The worms need to somehow evaluate a whole spectrum of conditions to decide

whether they want to try this food source or go out and look for a better one.”

Cornelia I. Bargmann

Six worms on a small lawn of bacterial food (circle). Occasionally, a worm

leaves the food to explore the surrounding environment.

Video: Bendesky et al. Nature

C. elegans thrive in agricultural settings, such as orchards and crop lands,

feeding on bacteria from rotting fruits and vegetables. But eating in this

environment is tricky: the worms encounter many bacterial species that are

difficult to digest or even toxic. " The worms need to somehow evaluate a whole

spectrum of conditions to decide whether they want to try this food source or go

out and look for a better one, " Bargmann says.

The great scientific advantage of using C. elegans to study complicated

behavioral processes such as decision-making is that the worms have only 302

neurons, and the connections between all those neurons have all been precisely

mapped. In contrast, the human brain has billions of neurons. What's more, most

of the worm's 20,000 genes have equivalents in the human genome. " Behavior

includes the action of genes, their function in neurons, and the neurons'

assembly into circuits, " Bargmann says. " Studying C. elegans gives you an

exceptional ability to make connections between those levels. "

Over the past decade, her lab has probed several of these levels. In 2004, they

reported that C. elegans sense precise oxygen concentrations in soil, which

helps steer them toward their favorite meal: oxygen-consuming bacteria. Three

years later, they investigated what neurons do with chemosensory information,

finding that odor-sensing neurons can switch on other cells that control

crawling and turning behaviors.

In the new study, Bendesky and Bargmann went one level deeper, investigating how

genetic tweaks can change a worm's behavior in particular circumstances. To do

their experiments, the researchers placed hundreds of different strains of C.

elegans onto Petri dishes lined with a circular " lawn " of bacteria and

calculated the rate at which worms left the lawn. " Lawn-leaving is something

that occurs abruptly, in an all-or-none way. It's very striking, " Bargmann says.

To find the genes that affect the behavior, they collaborated with HHMI

investigator Leonid Kruglyak and his postdoc Matt Rockman to use a technique

called quantitative trait locus analysis, they then analyzed the precise genetic

make-up of each strain and correlated it with how frequently each strain left

its lawn. In the end, the researchers could pinpoint particular genetic blips

associated with moving away from a food source.

One of those blips crops up in a gene called npr-1, which had already been

associated with foraging behaviors and immunity in the worm. The npr-1 variant

is a special case, however, because it evolved in laboratory strains of C.

elegans and is not known to exist in the wild.

In a more exciting development, the researchers also found a natural genetic

variation in tyra-3 that is associated with lawn-leaving. This gene encodes a

receptor protein that responds to tyramine, an adrenaline–like hormones derived

from the amino acid tyrosine. Like adrenaline, tyramine is an internal signal

that regulates the function of neurons expressing its various receptors.

To find out where in the brain the tyra-3 gene is turned on, the researchers

engineered strains of worms in which they could observe production of tyra-3. By

attaching a fluorescent green marker to the tyra-3 protein, they could easily

observe whenever the protein was made. They then traced where the green

fluorescence appeared inside the worms and discovered that the tyra-3 receptor

is produced in a place that makes intuitive sense: sensory neurons. In these

neurons, external cues, such as oxygen levels, can be integrated with internal

states, such as hunger. " It’s the result you would have gotten if you made it

up, " Bargmann says, laughing.

The findings show that particular genetic variants lead to specific behaviors in

the real world—but how, exactly, they do this is still mysterious. " We don't

have a fix on when tyramine is being made, where it's released, and how it's

working to change behavior, " Bargmann says.

Figuring that out is the obvious next step. The trouble is, the tools for

tracking the brain's chemical messengers in real time don't exist yet. " We'll

just have to put our heads down and develop some, " she says.