Tick genome study sheds light on occurrences of Lyme disease

Feb 12 2016

After a decade-long research effort the genome of the deer tick has been sequenced by an international team of scientists, including researchers from the SIB Swiss Institute of Bioinformatics. Studying the tick genome sheds light on how ticks function and will help to develop novel tick control programmes by interfering with the processes of disease transmission. The deer tick transmits Lyme disease and other diseases, which cause thousands of human and animal deaths annually. With about 10,000 new patients each year, occurrences of Lyme disease in Switzerland are amongst the highest in Europe, representing a substantial healthcare cost and threatening Swiss tourism.

Sequencing the genome of the Ixodes scapularis tick was a decade-long project, led by Purdue University entomologist Catherine Hill, and involving 93 scientists from 46 institutions, including researchers from the SIB Swiss Institute of Bioinformatics, the University of Geneva Medical School, and the University of Lausanne's Centre for Integrative Genomics.

I. scapularis is the first tick species to have its genome sequenced, with the results published in the journal Nature Communications. Known as the deer tick or blacklegged tick, the genome of this disease-carrying arachnid helps to shed light on how ticks acquire and transmit pathogens and offers tick-specific genetic targets for developing novel control programmes. "The genome provides a foundation for a whole new era in tick research," said Prof. Hill, lead author of the paper, "now that we've cracked the tick's code, we can begin to design strategies to control ticks, to understand how they transmit disease and to interfere with that process." The U.S. National Institutes of Health, including the National Institute of Allergy and Infectious Diseases, and the U.S. Department of Health and Human Services provided principal funding for the project.

A substantial impact on global public health. Ticks primarily spread disease by creating a feeding wound in their host's skin, regurgitating infected saliva into the wound as they ingest blood. Despite their capacity to acquire and pass on many pathogens, research on ticks has lagged behind that for other vectors, such as mosquitoes, largely because of a lack of genetic tools and resources. "Ticks are underappreciated as vectors - until you get Lyme disease," Prof. Hill said. In Switzerland the disease is estimated to cause 10,000 new infections per year. About 30,000 cases of Lyme disease infections are reported in the United States annually, but the U.S. Centers for Disease Control and Prevention estimate the actual number of cases at 329,000 a year, as many are unreported or misdiagnosed. While not fatal, Lyme disease can be permanently debilitating if it is not treated before it reaches the chronic phase.

In addition to Lyme disease, the deer tick vectors human granulocytic anaplasmosis, babesiosis, and the potentially lethal Powassan virus. Other tick species transmit several flaviviruses, including some that cause haemorrhaging and inflammation of the brain and spinal cord. Less is known about diseases caused by the flaviviruses than Lyme disease, but they are particularly important diseases in Europe and parts of Asia and represent global threats to human health.

New genomic resources to help understand tick biology. Identifying the proteins involved in the transmission of tick-borne diseases could help develop strategies to halt this process. "Genomic resources for the tick were desperately needed," explained Prof. Hill. The genome sequence has allowed researchers to pinpoint proteins in the tick genome associated with the transmission of human granulocytic anaplasmosis, and some of the proteins that play key roles in the interactions between deer ticks and the bacterium that causes Lyme disease. The genome also provided a closer look at unique aspects of tick biology, including their multitasking saliva, which contains antimicrobials, pain inhibitors, cement, anticoagulants and immune suppressors, all designed to help the tick feed on its host undetected for days or weeks. The genome revealed that tick saliva contains thousands of compounds - compared with only hundreds in mosquito saliva - "a diversity that presumably allows ticks to exploit a wide range of hosts and stay attached for a long time," said Prof. Hill.

The researchers also identified genes that could be linked to ticks' ability to synthesise new armour-like cuticle as they feed, allowing them to expand their body size over 100 times. They also examined the genome for clues to how ticks digest blood, which is toxic due to high concentrations of iron, and found a number of proteins that link with iron-containing haem molecules to make them less toxic.

A very large and complicated genome. One of the main challenges the research team faced stemmed from the large size and complexity of the tick genome. The deer tick has one of the largest arthropod genomes sequenced to date - about 1,000 times larger than the well-studied Drosophila fruit fly. This large size is mainly attributable to the accumulation of large regions of repetitive DNA. "As protein-coding genes are made up of sets of DNA sequences called exons that are separated by non-coding regions called introns, the presence of large DNA repeats in the introns mean that tick genes can be very long indeed," said Dr Robert Waterhouse from the SIB Swiss Institute of Bioinformatics and the University of Geneva. Comparing the tick gene structures to those of other arthropods as well as other animals revealed a rather surprising finding, "tick gene architectures are more similar to those of mammals than to insects," explained Dr Waterhouse, "suggesting that while insect genes have undergone many changes in their exon-intron structures, ticks and mammal genes have experienced fewer changes and more closely resemble the intron-rich gene architecture of the last common ancestor of all animals."

The SIB researchers have studied the genomes of many insects and other arthropods, including that of the bed bug, Cimex lectularius, also recently published in Nature Communications. "Our research focuses on the genomics of arthropods that are helpful or harmful to humans," detailed Dr Waterhouse, "learning about the tick and the bed bug is important for human health, and in the case of the bed bug it is particularly of interest to the hotel and tourism industry." The large and complicated tick genome provides new insights into how genes and genomes have evolved. These genomic resources offer many new opportunities to explore the biology of the deer tick to help prevent outbreaks of tick-borne diseases that threaten our enjoyment of the countryside.