ABOVE: Top (left to right): Western chimpanzee (Pan troglodytes verus) in Bossou, Guinea, Japanese macaque (Macaca fuscata) in Yakushima, Japan, Blue monkey (Cercopithecus mitis) in Kalinzu, Uganda
Bottom (left to right): Bornean orangutan (Pongo pygmaeus) in Danum Valley, Borneo, Malaysia, Anubis baboon (Papio anubis) in Kalinzu, Uganda, Javan lutung (Trachypithecus auratus) in Pangandaran, Java, Indonesia

Most people enjoy umami flavor, which is perceived when a taste receptor called T1R1/T1R3 senses the amino acid glutamate. In some other mammals, such as mice, however, this same receptor is much less sensitive to glutamate. In a new study published August 26 in Current Biologyresearchers uncover the molecular basis for this difference. They show that the receptor evolved in humans and some other primates away from mostly binding free nucleotides, which are common in insects, to preferentially binding glutamate, which is abundant in leaves. The authors argue that the change facilitated a major evolutionary shift in these primates toward a plant-heavy diet.

“The question always comes up about the evolution of umami taste: In humans, our receptor is narrowly tuned to glutamate, and we never had a good answer for why,” says Maude Baldwin, a sensory biologist at the Max Planck Institute for Ornithology in Germany. She was not involved in the new work, but coauthored a 2014 study with Yasuka Toda, who is also a coauthor on the new paper, showing that the T1R1/T1R3 receptor is responsible for sweet taste in hummingbirds. In the new study, the authors find “that this narrow tuning has evolved convergently multiple times [and] that it’s related to folivory,” she says, calling the paper “a hallmark, fantastic study, and one that will become a textbook example of how taste evolution can relate to diet and how to address these types of questions in a rigorous, comprehensive manner.”

In 2011, Toda, who was then at the University of Tokyo and now leads a group at Meiji University in Japan, and Takumi Misaka of the University of Tokyo developed a strategy to use cultured cells to analyze the function of taste receptors. They used the technique to tease out the parts of the human T1R1/T1R3 that differed from that of mice and thus underlie the high glutamate sensitivity in the human receptor, work that they published in 2013.

To use leaves as a new protein source, the ancestors of large primates (including humans) evolved their umami taste receptor as a sensor for glutamate.

—Yasuka Toda, Meiji University

As part of that project, Toda and Misaka also established a collaboration with Takashi Hayakawa, now a group leader at Hokkaido University in Japan, and Hiroo Imai, a biologist at Kyoto University. Both Hayakawa and Imai are affiliated with the Primate Research Institute at Kyoto University and thus have expertise in nonhuman primate biology, as well as access to genomic DNA for further receptor comparisons. In the 2013 study, the team found that among three nonhuman primates—squirrel monkeys (Saimiri boliviensis), baboons (Papio hamadryas), and macaques (Macaca nemestrina)—only squirrel monkey T1R1/T1R3 had very low sensitivity to glutamate, just like mouse T1R1/T1R3. “Thus, we hypothesized that the glutamate taste perception has been acquired during primate evolution,” Toda writes in an email to The Scientist.

In the new Current Biology study, Toda and colleagues test that hypothesis. First, they used Toda’s cell-culture strategy to make comparisons of glutamate sensitivity among the T1R1/T1R3 receptors from 17 species of primates. The receptors from all but four nonhuman primates—marmosets (Callithrix jacchus), tarsiers (Carlito syrichta), squirrel monkeys, and greater galagos (Otolemur crassicaudatus)—were sensitive to glutamate. These four species primarily rely on insects for protein. In contrast, the receptors from humans and gorillas were much less responsive to the free nucleotides inosine monophosphate and guanosine 5’-monophosphate than were the receptors from the rest of the primates.

The team then identified the protein building blocks responsible for either glutamate or nucleotide recognition by comparing the DNA codes for different species’ receptors and constructing chimeras between the spider monkey (Ateles geoffroyi, most responsive to glutamate) and squirrel monkey (most responsive to free nucleotides) receptors, which they then tested in cell culture. Substituting just two spider monkey nucleotides for squirrel monkey nucleotides was sufficient to switch the sensitivity from glutamate to free nucleotides, and vice versa.

The authors next explored the relationship between diet and receptor sensitivity. They found that leaves and fruit have a lower concentration of free nucleotides than do insects, and concentrations of glutamate higher than that of free nucleotides. The four nonhuman primates with a taste receptor specialized to detect free nucleotides primarily rely on insects as a protein source, while most of the other primates the researchers studied include leaves and fruit as a large proportion of their diets. In a final test of one species’ preferences, the researchers showed that squirrel monkeys prefer to drink water that has added free nucleotides, but show no preference for water with monosodium glutamate added.

The diversity of methods that the authors use to address how the genetic evolution of taste receptors occurred in conjunction with dietary patterns is “impressive,” says Addison Kemp, a biological anthropologist at the University of Southern California Keck School of Medicine who did not participate in the study. One open question, she adds, is what patterns of taste receptor sensitivity to glutamate are present in the lineage that includes lemurs and lorises, only one of which—the ring-tailed lemur—was included in the current analysis.

The researchers showed in the study that the ring-tailed lemur T1R1/T1R3 receptor demonstrates affinity for both glutamate and free nucleotides, “but that is their one representative from this really, really diverse clade,” Kemp explains. Plus, lemurs and lorises “tend to retain a better sense of smell, as they have a wider range of functional olfactory genes, and the interplay between taste and smell is really important in terms of the ingestive experience,” she says, adding that, based on the paper, it sounds like the authors are planning to look at this group in the future. “It will be really interesting to see what kind of patterns they see in terms of taste receptor sensitivity to glutamate within this lineage.”

The findings indicate that “sensory systems are very flexible and can evolve new adaptive sensory capabilities,” Toda writes. “To use leaves as a new protein source, the ancestors of large primates (including humans) evolved their umami taste receptor as a sensor for glutamate,” she explains, adding that this specialization for glutamate may have helped primates overcome bitter and aversive tastes also present in leaves.