Innovative research paves the way for genetic targets to reduce tick-borne diseases — ScienceDaily

Innovative research paves the way for genetic targets to reduce tick-borne diseases — ScienceDaily

A team of scientists led by the University of Maryland has released the first comprehensive continuous genome for a parasite responsible for transmitting Lyme disease and other serious infections to hundreds of thousands of Americans each year. With their newly described genome for the black-legged tick, or deer tick, the researchers identified thousands of novel genes and new protein functions, including proteins related to tick immunity, disease transmission and developmental stages.

This work provides valuable information for developing interventions for various tick-borne diseases, overcoming previous efforts to sequence the tick genome, which resulted in partial genomes or fragments of genomes with gaps and uncertainties.

The study was published January 19, 2023, in the journal Nature Genetics and was made possible by close collaboration between multiple academic institutions, industry and federal institutions.

“We are very excited to now have this reference genome, because there are so many unanswered questions about how these parasites evolved and how they transmit disease,” said Utpal Pal, senior author of the study and professor at the Virginia-Maryland College of Veterinary Medicine. in College Park. “We believe there are genetic factors that contribute to why these ticks are such good disease vectors, but we can’t really understand without a very good genome like this.”

black-legged ticks (Ixodes scapularis) or closely related species are widespread throughout North America, Europe, North Africa and Asia. They are primary vectors of several diseases, including Lyme disease, which infects nearly half a million Americans each year. However many aspects of their biology are unknown.

With a complete genome, scientists can begin to unravel the molecular mechanisms behind many aspects of the parasite’s biology and its interactions with both its host and the diseases it transmits.

The genome of a black-chested tick (expressed as a combination of four nucleotides represented by the letters ATCG) contains more than 2 billion discrete pieces of DNA code. Like letters strung together to form words in a sentence, the DNA codes are strung together into genes that make up the genome.

Previous work to decipher the tick genome used many immature ticks or tick cells grown in laboratories for several generations, which introduced errors, or combined samples from multiple individual ticks, which resulted in fragmented bundles of code with many redundant snippets. Researchers had to put the pieces back together, deciding where each gene starts and ends and how they should be arranged.

To overcome these challenges, Pal and his colleagues combined two methods to sequence the genome of an individual tick. One method deciphered the entire genome at once, creating a sequence that was complete, but somewhat “fuzzy,” meaning that the code was not clear in many places. In the second method, the researchers used a common technique called Polymerase chain reaction or PCR to “amplify” small parts of the genome so that it could be read more clearly. The team then combined the two results, which looked like a blurry image, using a big picture as a reference to put together high-resolution puzzle pieces. Finally, the researchers used a technique called “Hi-C” to bridge small pieces of DNA into longer, contiguous strands.

The result is a high-quality contiguous genome that is 98% complete. The new genome indicated that 40% of the annotations previously described for the black-legged tick relied on older technology and needed to be updated.

The researchers then compared their entire genome to bits of genome sequenced from 51 wild-caught ticks, showing that the new work could be used as a reference to identify parts of genetic material from other individuals. This also identified previously unknown genetic diversity among groups of ticks from different regions of the US

Finally, the team analyzed their tick genome to identify thousands of new genes and proteins and to describe new critical functions of those genes. For example, in one experiment, they found that some proteins were only present during certain stages of a tick’s life cycle or at specific stages during a tick’s blood meal and digestion. By knocking out a gene that tells tick cells to make one of those proteins, they were able to interfere with the tick’s feeding and digestion process.

Future work like this could help target gene-based therapies and vaccines that interfere with some part of the disease transmission cycle between ticks and humans.

An additional result of the study was that the researchers identified and described a more comprehensive genome for Rickettsia booksthe pathogenic bacteria that cause rickettsiosis.

The genomic resources described in the paper are publicly available through large databases and will help advance tick research and preventive measures.

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