Allergies and the connected world

The modern society offers many technological advances making our lives easier. One of the perks is the possibility to travel in remote areas on the world effortlessly, as easy as buying an air ticket on a travel website. What people might not realize when they board a plane, is that they can share the flight with myriad of microscopic passengers also enjoying the technological progress to their own benefits. Similarly to humans, they can visit new places, establish a new population, expand their ranges, and interact with other organisms through various means. House dust mites are not an exception. They can easily travel on passengers' clothes, skin, food, and baggage. These little creatures are responsible for causing allergic disease in 65 million to 1.2 billion people worldwide. But what is the link between allergy and the ongoing process turning our planet into a giant interconnected network?

Researchers at the University of Michigan and Tyumen State University conducted a study examining the level of connectivity between mites' populations in the USA and Asia. We studied genetic variation in the group 1 allergen gene, encoding the most important allergy causing protein. Inactive form of this protein is used in every clinic in the world as part of the standard skin prick test. Briefly, a small amount of this protein is administered under the skin; if there is an immune response, then house dust mites are blamed for the patient's allergy. If the test does not include local variants of the protein, then it can be inaccurate. Surprisingly, geographic variation of group 1 allergen protein has not been studied in the USA, although the data are available for other countries: the UK, Australia, China, Korea, and Thailand. Aside for the medical significance, knowing variation of the group 1 allergen gene can shed some light on the pattern and frequency of mite migration. The presence of common mutations across mite populations would indicate a greater connectivity between populations, while the presence of unique and geographically isolated mutations would suggest a greater level of separation between the mite populations and their inability for intercontinental dispersals. In other words, every time a mite successfully migrates to a new place, it brings its own genetic signature that can be detected in the acceptor population a long time after the migration event. If migrations are very frequent, the majority of mutations will be shared, erasing all geographical structure from the original populations. One can say that there is a single panmictic population, even though the mites are separated by the ocean.

What we have found suggests that mites' populations are indeed linked through migration across continents, although, they were not entirely panmictic – geographic differences still can be detected. Our study was focused on two most important species, the American and the European house dust mites. Both mite species have global distributions, but the former, as its name implies, is more abundant in the USA. These two species have separated from each other nearly 81 million years ago, much before the origin of humans (4.1 Mya based on fossil evidence). This is enough time to accumulate many mutations in the group 1 allergen gene and form many geographically isolated variants in the absence of frequent dispersals.

Based on our research, the majority of mutations were silent, meaning that they occur at the DNA level, without changing amino acid structure of the group 1 allergen protein. This is good news. Only mutations at protein level would have a medical significance because they can cause changes in allergenic properties. Knowing this, we intensely hunted for mutations changing structure of the protein. For this purpose, we used a more accurate technique, greatly increasing the detection success and decreasing error rates. The most unexpected result was the finding of a previously unknown mutation (tryptophan to arginine), occurred at the active site of the protein at position 197. This was a rare mutation, found only in a single population of the American house dust in Southern Asia. Based on bioinformatics analysis, this mutation might alter the enzyme activity, but allergenic properties, immune response, and cross-reactivity of the protein are unknown. Follow-up experiments to elucidate these issues are underway in our lab.

House dust mites have been around a long time before the origin of humans. Nests of birds and mammals, having conditions resembling those of human habitations, are their natural habitat. House dust mite populations are currently admixed via human activities, so rare geographical variants can spread across the entire range of mites. No one can predict how this can affect allergy sufferers. In order to understand this process and risks associated with it, more investigations are needed. Most importantly, we need to have a better idea about the diversity of allergenic proteins around the world, and in particularly in the USA.

This research was conducted at the Prof. Barry OConnor's laboratory at the University of Michigan by Rubaba Hamid and Pavel Klimov, a Leading Researcher of Tyumen State University Acarology Laboratory. This work was supported by the US National Science Foundation, Higher Education Commission (HEC) and International Research Support Initiative Program (IRSIP) in Pakistan, the Ministry of Education and Science of the Russian Federation, and the US National Pediculosis Association (NPA).

Manuscript title: Group 1 Allergen Genes in Two Species of House Dust Mites, Dermatophagoides farinae and D. pteronyssinus (Acari: Pyroglyphidae): Direct Sequencing, Characterization and Polymorphism
Journal: PLOS ONE

Authors: Rubaba Hamid Shafique, Pavel B. Klimov, Muhammad Inam, Farhana Riaz Chaudhary, and Barry M. O’Connor