Adequate intake of dietary essential amino acids (eAAs) is vital for protein synthesis and metabolism. Any single eAA deprivation is sufficient to increase protein intake in the fruit fly, Drosophila melanogaster. How such nutritional “needs” are transformed into behavioral “wants” remains poorly understood.
In a new study published in Current Biology titled, “Lack of single amino acids transcriptionally tunes sensory systems to enhance microbiota intake,” researchers from the Champalimaud Foundation have derived transcriptomes from the heads of flies deprived of individual eAAs to identify mechanisms by which this is achieved. While specific eAA deprivations have unique effects on gene expression, a large set of changes is shared across deprivations.
“While the flies’ behavior was similar across all amino acid deprivations, showing an increased drive to feed, each deprivation had its own unique ‘fingerprint’ in terms of gene expression,” says Gili Ezra-Nevo, PhD, postdoctoral fellow at the Champalimaud Foundation and the study’s first author. “But despite those differences, some genes changed in the same way no matter which amino acid was missing.”
Using synthetic diets that each lacked one of the ten essential amino acids, the researchers sequenced RNA (ribonucleic acid) from the heads of flies in eleven different conditions—ten amino-acid-deprived diets plus one fully balanced control. This allowed them to track how the expression of thousands of genes changed depending on which amino acid was missing.
Two olfactory receptor genes, Or92a and Ir76a, were consistently upregulated in response to amino acid deprivation.
Or92a was already known to respond to diacetyl, a molecule that contributes to the smell of wine and beer. As yeast—which contains all essential amino acids—produces diacetyl during fermentation, results showed the smell attracted protein-deprived flies.
When the researchers tested flies lacking Or92a, the insects were able to locate yeast but showed low feeding levels. “They could smell where it was, but it didn’t taste as good to them,” Ezra-Nevo explained. “That’s because olfaction isn’t just about finding food—it also contributes to flavor and the evaluation of palatability.”
Using a mutant strain of yeast that didn’t produce diacetyl, flies were less likely to feed as losing that key olfactory cue disrupted their sense of flavor and made the food less appealing.
Fermented foods such as cheese and chocolate emit a compound called PEA, which activates Ir76a. Testing showed that flies’ olfactory neurons responded strongly to the odor of chocolate but not to cheese. Both foods are fermented by Lactobacillus and Acetobacter bacteria, which also produce the same compound.
“That’s when things clicked,” says Sílvia Henriques, PhD, postdoctoral fellow at the Champalimaud Foundation and the study’s co-first author. “The flies weren’t being attracted to the chocolate itself—they were responding to the bacteria growing in those foods. And those bacteria are also natural residents of the fly microbiome.”
The study uncovers how internal physiological states shape perception and behavior. Looking ahead, the research can expand to reprogramming sensory receptors to enhance fitness across multiple nutritional deprivations.