Bed bug genome shows how gnarly these creatures really are

The bed bug is hardy, nasty, and well adapted to our homes, new analysis of its genome confirms. The work also corroborates previous findings on how the bed bug has developed resistance to modern insecticides — and may lead to new ways to control the pest.

The bed bug’s genome, published in two Nature Communications papers by two groups of researchers, includes relatively few genes associated with smell and sight. That’s likely because it isn’t hard for the bed bug to find us across our bedrooms. The insect is "very highly adapted to being a small ectoparasitic pest that lives by its host," says Josh Benoit, an insect molecular biologist at the University of Cincinnati and first author on one of the papers.

The research shows that the bed bug has genes that help it feed. Examples include genes that make salivary proteins, which prevent blood from clotting, and digestive proteins, which may allow the bloodsucker to take multiple bites during a feeding. The bed bug also has an unusually high number of genes that make an elastic protein called reslin. Reslin in the female bug’s exoskeleton may provide protection during an intense mating ritual where the male stabs a needle-like penis into the female’s abdomen and ejaculates into her body cavity.

The work is part of a trend toward an ambitious goal: to sequence the DNA of all known living things

The new papers represent a larger trend in genomic research. In the field’s early days, scientists focused on model organisms — species common across labs, such as the fruit fly, mouse, or zebrafish — as well as those that are medically or economically important. Now, the technology is cheap and fast enough to allow for non-standard organisms. The work is part of a trend toward an even more ambitious goal: to sequence the DNA of all known living things, or at least as many as scientists can access.

"I think maybe it’s time to start thinking about describing life on Earth at the molecular level — the same way that Google Maps will give you maps of everywhere on Earth," says Stephen Richards, a genomicist at Baylor University and head of a pilot study from the i5K Project, which eventually plans to sequence the genomes of 5,000 insect species ("The Manhattan Project of Entomology," as it’s sometimes called).

Whole genome sequences — essentially all of an organism’s DNA — provide blueprints for scientists and help to decipher the genetic origins of the organism’s appearance, function, and how it responds to its environment.

Having this genetic map "fundamentally changes the research questions you can ask," says Jeffrey Rosenfeld, a bioinformatics expert at Rutgers University and the American Museum of Natural History and a first co-author on the other paper. As for the bed bug, he adds: "It’s a complicated genome. They’re just weird creatures."

The two teams decided to work on the bed bug genome for different reasons. The i5K team decided to use bed bugs in a pilot project that started in 2012, along with other recognizable urban pests such as the German cockroach, agricultural pests including the Colorado potato beetle, and generally interesting insects such as the dragonfly and the dung beetle. The same year, the second group, led by scientists at AMNH and Weill Cornell Medicine, chose the bed bug as a pilot for sequencing full genomes at the museum. This group chose the bed bug because they consider it a "living fossil," as it hasn’t changed much over its long history, which may stretch back hundreds of thousands of years. It didn’t hurt that bed bugs are also iconic New York City pests.

At first, the two teams didn’t know they were competing — they usually hang in different scientific circles. Once the rivalry was confirmed, the groups kept their projects separate, partly because they were both far along in the work and partly for the competition. "We had this classic conflict. Do we reach out and try to all publish a paper together? Or do we race?" says Chris Mason, a geneticist at Weill Cornell Medicine.

But last July, both teams realized their papers were finished and under consideration at the same journal, and so they decided to ask Nature Communications to publish the work simultaneously.

While both teams sequenced the genome, they took slightly different tacks. The i5K team had a more traditional approach, focusing on the genome and covering it as thoroughly as possible. To put a genome together, scientists take the DNA from an organism’s cells and use machines to analyze its chemical makeup. In some cases, the scientists may rely on a computer to put the genome together, automatically analyzing it. In other cases, experts may go into certain regions to manually analyze specific sections and double check the computer’s work, which isn’t always accurate.

The i5K group did quite a bit of manual annotation, focusing are regions such as those associated with sight and smell. They also annotated genes already known to be related to insecticide resistance — which has particularly developed in response to a popular insecticide class called pyrethroids. Some sets of genes protect the bug’s nervous system against pyrethroids; make proteins that help bed bugs metabolize and detoxify the chemicals; and thicken the bed bug’s exoskeleton so it’s harder for the pesticides to penetrate.

That group also found evidence that bacteria that live in the bed bug’s body inserted DNA into the bed bug’s genome. Most of these genes came from Wolbachia, bacteria that live in the bed bug’s gut. Previous research shows Wolbachia help the bug synthesize vitamins. Only one of these genes may actually do anything in the bed bug. The protein this gene makes is similar to patatin, which is common to potatoes and helps store fats. If scientists confirm that this patatin-like gene is active in the bug — which is a big if — it could eventually be a good candidate for insecticides that target specific genes.

The team looked for evidence of bed bug DNA from new York's subway systemsWhile the AMNH team also sequenced the bed bug’s genome, they did fewer manual annotations, instead expanding their work to also look at how the genes function in the bug and how the bug interacts with its environment — unusual for a genome paper. For example, they compared changes across six stages of the bed bug’s life cycle and noted a flurry of genetic activity after the bug has its very first taste of blood. This activity is likely because the bed bug’s body is reacting to the new and foreign materials the meal introduces.

The team also tried to see how the bugs are distributed across the city. To do this, they looked for evidence of bed bug DNA in data from a previous project, which collected a range of DNA from 465 stations in New York’s subway system.

Don’t panic: this doesn’t mean bed bugs have permanently infested the subway. Instead, the authors say traces of bed bug DNA may have come into the subway stations on straphangers’ shoes or other belongings. These DNA fragments may show how different bed bug strains — bed bugs with slightly different genetic makeup — relate across a geographical region. The paper suggests that bed bugs in closer proximity to one another are more related, while populations are distinct between the city’s boroughs.

These results come with some caveats. For instance, the researchers aren’t sure the DNA fragments are actually from bed bugs — they may may be detecting an entirely different, but related, species. It’s also possible that the DNA found in the subway stations isn’t from an insect at all, cautions Jonathan Eisen, an evolutionary biologist at the University of California–Davis, who wasn’t part of either research team. "I think it’s interesting if they really found bed bug sequences in their subway data. But I’m not even remotely convinced from what they report here that is the case."

As genomics researchers aim for increasingly obscure research subjects, it gets more difficult to put together the genomes, says George Amato, the director of the AMNH’s Sackler Institute for Comparative Genomics. "For model organisms, you get the sequences and you kind of back them onto your structure."

Mapping a whole genome of a non-model organism, Amato adds, is more like "driving in the dark blind, and there are no guard rails and you’ve got no headlights."

mapping a whole genome of a non-model organism is more like "driving in the dark blind, and there are no guard rails and you've got no headlights."

The AMNH group envisions something similar to Richards’ Google-map-like level of genomic sequencing. The museum’s longtime mission is "to collect and catalog and characterize every species on the planet," says Mark Siddall, a curator in AMNH’s Division of Invertebrate Zoology and Sackler Institute for Comparative Genomics. "Eventually, one supposes that sequencing whole genomes will be not unlike taking photographs of the animals when they come in. I don’t think we’re there yet, but wouldn’t that be awesome?"

With limited money and resources, covering the same genome twice won’t exactly help reach this goal, but the fact that the bed bug teams took different approaches is helpful. "Frankly, genomes are getting to be fairly routine. It takes an interesting hook to present a genome in a way that’s really exciting and broadly appealing, and these guys just totally nailed it," says May Berenbaum, an entomologist at the University of Illinois at Urbana-Champaign, who wasn’t involved in the research. The papers are "complementary," she adds, "which is why they are both being published."

Next, the AMNH and i5K teams will collaborate on a new paper on the bed bug’s mitochondrial genome, which, because it’s passed only on the maternal side, can help trace population relationships through time.

"We used both groups’ data and we will publish it jointly," says Amato. "What could be nicer than another paper all ready to be submitted, but that’s a combination of the two groups working together?"