An eye for a nose?

At some point in our evolutionary history, we lost the ability to smell carbon dioxide. While humans and monkeys still have remnants of a gene that appears to be involved in carbon-dioxide detection, the gene no longer functions.

These findings by Dr. Janet Young of the Human Biology Division and collaborators at the University of Southern California appeared in the Oct. 10 online edition of PLoS ONE and add to recent research showing that rodents can smell carbon dioxide, or CO₂, in the environment. Since all animals exhale CO₂, scientists speculated that rodents could detect the presence of other animals, including predators, by sensing how much CO₂ is around — that is, how many other animals are exhaling nearby.

"You might want to detect CO₂ if you're in a very confined space, like a mouse nest, and you need to determine when you need to get more fresh air. Or you might need to detect other animals in close proximity based on the CO₂ in their breath," Young said.

Humans, who have few predators and generally don't live in crowded, confined nests, might have no use for detecting CO₂ in their immediate environment. But this isn't a unique event in our evolutionary history. "It's part of a general decline in our ability to smell things," Young said.

Humans are bad smellers. All mammals have a main olfactory system, otherwise known as the nose. But rodents and some mammals also have what Young termed a second nose, the vomeronasal organ. Historically, scientists thought the nose was for smelling environmental smells and the vomeronasal organ for detecting pheromones, chemical signals used to communicate between members of a species. But more recently, it has become clear that the nose can detect pheromones too.

Young's study confirmed previous hints that a specific gene in cells that detect carbon dioxide in rodents is mutated severely enough in humans that it can't possibly work. These non-functional pieces of DNA that used to be genes are termed pseudogenes.

Most of the nerve cells in our nose express proteins called odorant receptors. Each receptor is specific to a certain smell or set of smells — molecules in the air bind these receptors and cue the nerve cells to signal the smell to our brain. But in rodents, a separate subset of olfactory nerve cells expresses the protein guanylyl cyclase-D, or GC-D, instead. These nerve cells appear to be functionally different from other nerve cells in our nose and seem to respond to carbon dioxide. Another recent study shows these cells may also respond to pheromones found in mouse urine.

Collaborator Dr. Hans-Jürgen Fülle, while at the University of Southern California, confirmed that the gene for GC-D was a pseudogene in humans by looking at the DNA sequence. He found several different mutations in the sequence, and some of these mutations are drastic enough that the gene could no longer function.

The search for GC-D

Together with Dr. Emily Liman, associate professor of neurobiology at the University of Southern California, Young decided to look at our closest evolutionary relatives to see when we might have lost the ability to detect CO₂. They gathered DNA sequences from public databases and sequenced samples provided by the San Diego Zoo for the GC-D gene in a variety of primates. They found that GC-D is a pseudogene in all apes, Old World monkeys and New World monkeys. That is, gorillas, spider monkeys, orangutans and the like probably cannot sense CO₂. Even the distantly related prosimian, the tarsier, is missing the GC-D gene.

Young had to go to lemurs and bushbabies, prosimians that are even more distantly related to humans, before she found something resembling a functional GC-D gene. Based on these results, Young believes that the ability to sense CO₂ was probably lost more than 40 million years ago in the common ancestor of tarsier and the "simians" (Old and New World monkeys and apes).

A number of published studies indicate that the ancient human ancestor lost a functional vomeronasal organ along with many odorant-receptor genes around 25 million years ago. Young doesn't think this massive loss of olfactory function in our evolutionary past is a coincidence. Several investigators have noted that human ancestors probably acquired trichromatic vision — the ability to see three colors, where most animals only see two-at around the same time that olfactory function declined.

Our improved vision may have made a refined sense of smell unnecessary, Young said. As for pheromones, which are largely used to signal between members of the same species, our keen vision could have rendered some of these obsolete, too. "Some primates can use colors to signal to each other when they're ready to mate. Or maybe our brains took over from other parts of our body," Young said. "We've acquired skills that make chemical communication less important. We like to think we're intelligent; maybe we've just figured out other ways to communicate."

The National Institutes of Health funded the study.

[Dr. Rachel Tompa is a freelance writer and student in the UC Santa Cruz Science Writing Program.]