The phrase “warm summer evenings” sounds like an offer of a lazy, peaceful, relaxing respite. Any peace, however, will almost certainly be temporary, interrupted by an annoying buzz that signals it’s time to start swatting away and, if that doesn’t work, spend the rest of the night scratching some itchy welts.
By the time you hear its buzz, the mosquito has already engaged in a multisensory program that started by picking up your scent and the increased levels of carbon dioxide coming from your breath. By the time it’s close enough for you to hear it, it’s picking a place to land on you based on the fact that your skin temperature is even warmer than the summer air.
Interfering with this multisensory program holds the potential to not only improve your enjoyment of summer evenings; it could play a major role in limiting a variety of insect borne diseases that collectively kill millions of people each year and exact a staggering toll beyond that. But to interfere with the system, we have to understand it. And a key step toward that has now been provided by the identification of the protein that lets the mosquito sense that we’re warmer than the environment. Unfortunately, that knowledge has enabled us to confirm that wiping out the heat-sensing part of the system is unlikely to protect us.
More like flies than FLIR
Given the examples familiar to us, like night-vision goggles and FLIR systems, you might think that sensing heat is pretty simple: just retune the proteins we use to sense visible light so that they pick up infrared photons instead. But it’s not that simple. The receptors that respond to photons do so by using the photons’ energy to alter a chemical bond. Infrared photons just don’t have enough energy to make that happen.
To figure out what mosquitos use instead, a Boston-based team of researchers focused on their evolutionary relatives. While it’s possible that mosquitos evolved an entirely new way of sensing temperature, it’s more likely that they simply repurposed an existing one. Many other insects have had temperature-sensitive proteins identified, and they’ve been especially well characterized in the fruit fly Drosophila. So, the research team reasoned, one of those is likely to be involved in using temperature to identify feeding targets.
Fortunately, some early work had eliminated a number of candidates. Two proteins that fruit flies use to sense heat have been tested in mosquitoes, but they seemed to operate identically in the two species, which have very different feeding habits. (One of them, for example, helps both fruit flies and mosquitoes avoid locations with extreme heat). So instead, the team turned to a set of three proteins that are used to sense temperatures more generally by providing the fly indications on when temperatures are too hot or too cold.
Since both the fly and mosquito genomes have been sequenced, it was a simple matter to find the mosquito versions of each of these genes. With that knowledge, the researchers were able to figure out where each of them was active. One of them, Ir21a, was active in just the right place: the tips of a few structures in the antenna. This was true in both male and female mosquitoes, even though the males don’t feed on other animals.
Feel the chill
To find out how this affected mosquito behavior, researchers used the CRISPR gene editing system to knock out the gene encoding Ir21a, using unedited mosquitoes as the control in further experiments. The first thing they did was hook electrodes up to the sensory structures where the Ir21 gene is active and expose the setup to changes in temperature. Strikingly, they found that the loss of the gene caused the loss of a signal that occurred when the environment was made colder.
This may seem counterintuitive as a way of telling a mosquito when it has gotten closer to a warm body. But identifying when you’re getting colder can be an effective way of directing you toward something warm, as anyone who played hotter/colder as a kid can attest.
It turns out that the signal had been identified previously and assigned to sensory neurons that picked up the name “cold cells.” But a detailed examination here suggests that’s a bit of a misnomer. These cells don’t become active when they’re exposed to something cold; instead, they’re able to pick up any change toward a cooler temperature, even if it’s just going from hot to warm. There’s clearly value to that, in the sense that a warm summer evening will probably leave most objects fairly warm yet still allow animals to be hotter than their surroundings. The cells were also extraordinarily sensitive, seeing activity increases of as much as 80 percent in response to temperature changes as small as a half degree celsius.
It’s not enough to be hot
The scientists, not being idiots, also answered the most obvious question: if we’ve eliminated the gene that mosquitoes use to pick out warm targets, will they feed less? The answer turns out to be somewhat disappointing.
The first tests looked promising. The researchers set up two blood samples beneath a thin membrane and then warmed one. Mosquitoes were then primed for feeding with some blasts of carbon dioxide and set loose. In total, 43 percent of the normal mosquitoes zeroed in on the warmed blood sample, while most of the rest didn’t land anywhere (the unheated sample was nearly devoid of mosquitoes). But when they tested the mosquitoes with a knockout of the Ir21a gene, only about 15 percent of them ended up landing for a meal. The authors suggest that this indicates there’s at least some residual heat sensitivity that isn’t dependent upon this specific gene.
To make matters more realistic, the researchers then got people to hold their hands still in an enclosure with mosquitoes. The mosquitoes were primed to feed by five human breaths. And here, there was no significant difference between the total number of normal and mutant mosquitoes that landed on the victim’s volunteer’s hands. The mutants were a bit slower to accumulate there and more prone to scattering when the hand was moved, but they would eventually reach similar levels if undisturbed.
While unfortunate, this shouldn’t really surprise us. As mentioned earlier, mosquitoes use multiple cues to zero in on their source of meals. Knocking out a single part of that system was unlikely to completely eliminate its function. But if it turns out we need to knock out more than one to protect ourselves from these disease vectors, then it’s not a bad thing to understand them all—at least that way, it might be possible to figure out which ones are easiest to disable.
Science, 2019. DOI: 10.1126/science.aay9847 (About DOIs).