Parasites are a common theme of biological research due to the impact they have on people’s lives and their ubiquity in organisms around the world. It is practically impossible to find an organism that doesn’t have some sort of parasitic pathogen on or inside them. Even many of the parasites themselves have parasites inside of them. A related area of study includes the organisms that often lead a semi-parasitic lifestyle, but are more known to cause allergenic responses in humans more than anything else.

Dusty Parasitism

There is one set of species that fill this niche, but without being parasites themselves now and that detail is one of the more intriguing parts of their evolutionary history. The dust mites, usually of the genus Dermatophagoides, are a group of organisms that cause one of the familiar forms of allergen, which they are appropriately named after. Their background also involves their descent from a parasitic ancestor with an incredibly plastic genome.

The formation of a parasitic lifestyle often requires drastic genetic rearrangements in a short period of organismal time for a species. But even with that niche having been exploited after significant alteration, it appears that dust mites themselves might have been born from another series of massive changes to their genome removing them from that same life cycle.

The source of this severe instability is what are known as transposable elements (TEs), sequences of DNA that are able to move around the genome freely during offspring creation. In many ways, they are a detriment to the individual, as they have a high possibility of interfering with the function of other genes and causing their own cellular organism to die because of that. But on a wider population level, these elements are incredibly helpful for pushing rapid evolutionary change.

Silencing Variation

There is a point however where the cells have a need to restrict and reduce the activity of these TEs for the good of the organism. The more common method of doing so is by using RNA interference and silencing mechanisms. The Argonaute protein family and the RNA-induced silencing complex (RISC) are the most frequent biological form taken by these processes and can be found all across the tree of life. Usually microRNAs (miRNAs) and small interfering RNAs (siRNAs) are the genetic devices chosen for indicating what elements need to be silenced.

Vertebrates and invertebrates, however, focus on another option for their RNA silencing systems, the so-called Piwi-interacting RNA (piRNA). These specialized forms of the Argonaute/Piwi protein systems target transposons and their subtypes in particular. Therefore making them a prime candidate of topic when talking about dust mites. Control of TEs through piRNAs is, as stated, frequent in animals, though there are cases with nematodes and a few other species where the mechanisms were lost and they fell back on the Dicer and RNA polymerase options for controlling RNA silencing.

This RNA dependent RNA polymerase (Rdrp) converts the RNA forms of the transposable elements into double-stranded RNA, which are then cleaved by Dicer into short forms that work to silence their original genes. The term for this is RNA-induced transcriptional silencing (RITS) and is found in plants and fungi. As already noted, some nematodes utilize this too thanks to having the Rdrp protein, which is lacking in all other invertebrates and vertebrates.

Except for the Chelicerata subphylum, of which dust mites are included. These species are fairly unique in having both Rdrp and Piwi proteins, a dual system of silencing that are already known to control TEs at the same time. One might guess that this raises the complexity of the mechanisms greatly. So there hasn’t been too much research diving into that convoluted structure.

A Genome of Confusion

Now, researchers at the University of Michigan have decided to do just that and to see if these special RNAi arrangements might be able to shed light on other possible uses of silencing technology elsewhere in biological organisms and by humans. Their focus was on the particular dust mite species of Dermatophagoides farinae.

Of course, as is typical with such things, everything became perplexing almost immediately. Sequencing the genome of the American dust mite immediately returned the fact that these organisms have no Piwi RNA genes. They still have Piwi proteins encoded, but they don’t belong to the Piwi clade of functional proteins. They appear to have a unique Argonaute clade that has never been seen before. So even calling them Piwi proteins is incorrect. Orthologs to the sequences were identified in some spider species and C. elegans, but they are also of unknown function in those creatures as well.

The next step was to see if the dust mites have the co-functional piRNAs that go with the Piwi proteins. The spider mite genome was used as a comparison to see if equivalent gene sequences existed. What was found is that the dust mites seem to have completely lost the piRNAs and instead co-opted siRNA-like products cut by Dicer. When scanning the genome, a wide number of short non-coding RNAs were found that seemed to serve the purpose of the previously mentioned silencing sequences, but while similar to known siRNAs, they were still unique and lacked similarity to known sequences.

Evolutionary Volatility

In general, the dust mites were seen to lack single-stranded RNA genes, as would be needed normally for silencing activity. While it is possible that piRNA was still there in a double stranded form, the lack of what is called the “ping pong cycle” that helps to make more of them suggested this wasn’t the case. The piRNA pathway seems to have been entirely lost and that some sort of novel siRNA pathway has taken over control of dealing with transposable elements.

When looking at their Dicer systems for making siRNA, D. farinae was discovered to have 3 separate proteins. Their structure and lacking of several critical pieces suggests that their Dicers are from an ancient biological line that diverged and was lost in nematodes and all other insects and crustaceans. The first of these three was tested and evidence supporting its capability to process double stranded RNA was found, meaning that it is this Dicer that does indeed deal with TEs. The other two Dicers, however, also appear to play some role even while lacking that same processing, as knocking each of them out impacted the expression of TEs.

The Versatility of RNAi

Overall, it can be presumed that the dust mite family lost their piRNA creation abilities thanks to the rapid genomic changes their ancestor underwent in order to move to a parasitic lifestyle. Though that last part in terms of timing is just speculation. But the loss of the piRNA pathway did not meaningfully impact its RNAi silencing, leading to a solitary form of expression.

The distinct RNAi biology of dust mites focuses on unknown siRNAs produced by Dicer systems, comprising three-fourths of all small RNAs produced in the cells. This is highly unusual, as other organisms prefer microRNAs for these purposes. Additionally, these siRNAs seem to be involved in surveilling the genome to identify transposable elements as target sequences to silence. All three Dicer systems play a role in this in some manner, as depletion of any of them reduces their general silencing mechanisms.

Control of TEs is almost exclusively done by piRNAs, making the entire setup in dust mites novel to consider. This divergent schema gives an evolutionary look at how versatile small RNAs can be when parts are eliminated or altered. Such innovation may give new insight into how RNAi silencing mechanisms can be used and in what ways their functions differ depending on what components are applied.

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Photo CCs: CSIRO ScienceImage 11085 A scanning electron micrograph of a female dust mite from Wikimedia Commons

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