While the honeybee has a comparatively negligible role when it comes to pollination in the wild, that niche filled by the dozens of other bee species that are also often colony-less, they nonetheless have an important spotlight on them when it comes to human agriculture. This is so even if they only make up less than 30-40% of general crop pollination. They help to cross-breed some of the world’s farm crops, especially fruiting trees, and so research into their biology and how to keep them healthy is a key area of science. The field of melittology can range from covering the physiology of bees to their habitats to their overall wellness and even that can differ significantly between bee species.

An intriguing area of study that goes far broader than just bees is the weird involvement of RNA interference systems and environmental dsRNA. In the late 1990’s, it was discovered that certain species, often those very simple in nature, had the capability to uptake dsRNAs from their environment found from other organismal sources and that, if that dsRNA matched a gene in their own genome, would cause silencing of that gene. This type of mechanism has actually been found since to be utilized by host plants in order to destroy their parasite attackers through flooding them with dsRNAs that shut down their virulence genes. Of course, that is an ongoing and continually complicating arms race.

The Bee Mystery

This can also be used to target specific genes in agricultural crop pests and have the crops themselves express them, thus causing any pests that attack to essentially harm themselves in the process. But that’s a different topic, which you can read in a previous article. Back to the subject of honeybees.

Such a susceptibility to environmental dsRNA sources was also found to exist across a wide spectrum of invertebrates, including honeybees. Why such a thing existed was a mystery, but also raised several questions. Do these organisms perhaps transmit RNA signals to each other in such a manner for positive purposes, thus as a side effect leaving them open to other dsRNA entering their network?

Since we know such networks and also interspecies systems exist in plants and fungi, it would not be altogether surprising to find them elsewhere as well. Though it is still a conundrum, as it leaves them open to assault from not only parasites and pests, but also the most fundamental RNA user of all, viruses. Why leave such an opening to be exploited?

The Power of Royal Jelly

It is precisely that question that a research team from Israel and the University of Cambridge sought to uncover the truth to. The first thing they started with was pointing out that honeybees in particular have a notable plasticity in their development, as they can all go from larval stage to being a worker or a queen, all depending upon their ingestion of that infamous substance known as royal jelly. Their nutritional intake, in short, determines which path they will go, as developing queens require far higher levels of nutrition in order to begin the process of egg production. While worker bees are only fed royal jelly for their first 3 days of life, in order to boost their development time, queen bees are allowed to feed on the jelly for their entire lives, causing their transformation.

On a genome level, however, it has been seen that these nutritional changes have an epigenetic effect, methylating and thus silencing certain genes, creating a unique and differing expression of genes between workers and queen bees. The researchers further acknowledged that in their own previous studies, they had found that exposure of dsRNAs from dangerous bee viruses served as a sort of vaccine inoculation against actual infection in the future. The honeybees had taken up the dsRNAs and added them to their immune system memory. In many ways similar to how it works in humans, except we don’t use dsRNA to serve as memory, but antigens and antibodies instead.

That research showed them the effect existed, but the biology of how it worked was still unknown. Hence the point of the newly published study on the topic, two studies actually. The research team started off with using a molecular marker known as digoxigenin (DIG) to bind with the dsRNA being used for testing in order to determine where it is taken in the honeybee body after ingestion. After extracting hemolymph later, they were able to find the dsRNA in the fluid, indicating that the dsRNA had moved from the digestive system after being eaten and into the bee’s circulatory fluids.

This shows how honeybees might obtain foreign dsRNA and use it in their immune system defenses, but how would this defense get passed on to future generations? Even if the queen herself was inoculated, that didn’t guarantee proper exposure to the offspring larvae. But further testing quickly showed that, instead, the dsRNAs were incorporated into both the worker and royal jellies that are fed to larvae to condition their development. This ensured that they would all then be exposed to the same dsRNAs and develop the same protections against whatever pathogen that dsRNA belonged to.

A genetic investigation proved that royal jelly especially has high RNA-binding affinities, with a component they termed major royal jelly protein 3 helping to collect the RNA within the jelly. This collection is then organized into more cohesive forms called granules that help to protect the dsRNA from breaking down over time and essentially making the genetic material as shelf stable as the jelly itself. This allows for the jelly to be shared between all the bees in the hive and subsequent generations, to ensure they retain their immune system resistance against whatever pathogens the dsRNA came from.

Creating Immune Resistance

With this deeper understanding of the biological underpinnings of bee immune systems and how colonies pass on resistance traits, the research team hope this can be exploited to purposefully give the honeybees resistance ahead of time to pathogens they know will be encountered by bee-keepers, depending on the region in which the bees are to be grown. Varroa mites in particular would be a major candidate for forming an aggressive immune response to, as they are likely the primary culprit in honey bee deaths around the world year after year.

Press Article Link

Study Link #1

Study Link #2

Photo CCs: Bees Drinking Honey from Wikimedia Commons

About Sterling Ericsson