ADVANCES
16 Scientific American, May 2022Joao Paulo Burini/Getty ImagesB I O L O G YHunt for Color
Mosquitoes target red tones after smelling CO (^2)
A hungry mosquito can sense the carbon dioxide a person ex-
hales from 100 feet away, and a new study reveals that the gas
triggers the insect’s visual system to pinpoint human skin tones.
“The odor is just telling them that something is out there, but
their vision is telling them where it could be located,” says Universi-
ty of Washington neurobiologist Jeff Riffell, lead author of the study
in Nature Communications. Tracking 1.3 million mosquito trajecto-
ries, his team found that the insects are drawn to red and orange
light (which human skin prominently reflects, regardless of race)
and avoid most greens and blues—but only in the presence of CO 2.
Observing mosquitoes is hard; they dart through the air in
quick, chaotic patterns. Researchers typically examine them in
small boxes, but that “doesn’t recapitulate their natural behaviors,”
Riffell says. To simulate a more realistic environment, Riffell’s
team built a seven-foot-long mosquito wind tunnel that could
control wind speed, odors and visual stimuli with exquisite preci-
sion. Along the tunnel’s edge, 16 cameras captured live video
that was stitched together to reveal each insect’s flight path.
When Aedes aegypti mosquitoes were released into the tunnel,
they did not investigate objects colored to match human skin until
carbon dioxide was added. When it was, the mosquitoes flocked
to the objects. Filtering out orange and red light halted the attrac-
tion. In another experiment, the researchers introduced mutations
in the mosquitoes’ photoreceptors to suppress their vision for lon-
ger light wavelengths like red. This also stopped their swarming
toward human skin tones, as did mutating a CO 2 -sensing receptor.
“Given that mosquitoes do not have a separate red-sensitive
receptor,” says Almut Kelber, a sensory biologist at Sweden’s
Lund University who was not involved in the research, it seems
likely “that orange, red and black are all seen as dark and that the
choice is not for ‘red’ but for ‘not green or blue.’ ”
Other insects also use smell to cue visual preference. Female
Asian swallowtail butterflies, for instance, “make color choices de-
pending on the odor,” Kelber says. In a laboratory setting without
scents, they preferentially land on blue objects. But when swallow-
tails smell a larval host plant to lay eggs on, she adds, they move to-
ward green. Smelling oranges or lilies shifts their preference to red.
Riffell plans to extend his findings to develop better mosquito
traps. Many traps have white components, he says: “And mos-
quitoes do not like white at all.” — Niko McCarty
BIOENGINEERING
Inside Edit
A tool from bacteria informs a new
gene-tweaking technique
Deep in a bacterium’s gelatinous matrix dwell little “cellular
machines” called retrons, which produce single strands of DNA
to detect certain viral infections. Now for the first time,
researchers have used these natural DNA scriptwriters to
modify genes in human cells. A new study, published in Nature
Chemical Biology, suggests this technique can enhance gene
editing across diverse animal groups.
Although the well-known CRISPR process has made gene
editing much easier in recent years, it “has its own limitations,”
says the study’s senior author Seth Shipman, a bioengineer
at the University of California, San Francisco. This process
introduces an enzyme called Cas9 to cut DNA segments and
provides templates of desired DNA, designed by researchers, for
cells to incorporate during the repair process. But this template
DNA is created in the laboratory and must be inserted
separately from CRISPR’s components—and it does not always
penetrate the cellular membrane.
Shipman and his colleagues instead used retrons to manu-
facture that DNA inside the cell itself, where the CRISPR
process can readily use it. Retrons carry an enzyme called
reverse trans criptase that builds DNA strands based on RNA.
They also feature “some strangely overlapping loops of RNA”
that help them function, says Santiago Lopez, a graduate
student at U.C.S.F. and lead author on the study.
The researchers modified retrons in the lab so they would
produce the desired template DNA. Additionally, they
elongated the RNA loops, a change that turned out to let each
retron produce more DNA copies. Finally, they inserted the
retrons into cells along with CRISPR’s components.
Using this process, retrons produced from 10 to 100 times
more template DNA in yeast cells than in human cells. The
retrons also achieved better editing precision in yeast than in
human cells, possibly because of the differing number of strands
or the way each cell type repairs DNA. “But frankly, we are not
that worried right now,” Shipman says, “since this is only a foot in
the door.” He says more adjustments and optimization will likely
yield highly accurate editing in human cells.
“If we can repurpose retrons to produce DNA as ‘donors’
within a patient cell, it can be used for gene therapy applications
for diseases such as sickle cell anemia, which require repair of
only small stretches of faulty genetic sequences,” says University
of Nebraska molecular biologist Channabasavaiah B. Guru-
murthy, who was not involved in the study.
But introducing foreign DNA into human tissue cells can
also “elicit adverse immune responses that limit genetic modi-
fications,” says Jin-Soo Kim, director of South Korea’s IBS
Center for Genome Engineering, who was also not involved
in the work. Researchers who are using CRISPR alone have
developed processes to suppress such responses, Kim adds,
but it remains to be seen how to accommodate retrons.
— Saugat Bolakhe
Aedes aegypti can carry dengue and Zika virus.