Tiny Fruit Fly holds important genetic transfer discovery

A fruit fly genome doesn’t just consist of fruit fly DNA – at least for one fruit fly species. New research from the University of Maryland School of Medicine’s (UMSOM) Institute of Genome Sciences (IGS) shows that one species of fruit fly contains whole genomes of a type of bacteria, making this find the largest bacteria-to-animal transfer of genetic material ever discovered. The new research also sheds light on how this happens.

Julie Dunning Hotopp

Julie Dunning Hotopp

The IGS researchers, led by Julie Dunning Hotopp, PhDprofessor of microbiology and immunology at UMSOM and IGS, used new genetic long-read sequencing technology to show how genes of the bacteria Wolbachia have been incorporated into the flight genome up to 8,000 years ago.

The researchers say their findings show that, unlike Darwin’s finches or Mendel’s peas, genetic variation is not always small, incremental and predictable.

Scientist Barbara McClintock first identified “jumping genes” in the 1940s, such as genes that can move within or be transferred into the genome of other species. However, researchers continue to discover their significance in evolution and health.

“We didn’t have the technology before to unequivocally demonstrate these genomes that show such extensive lateral gene transfer from the bacterium to the fly,” explains Dunning Hotopp. “We used state-of-the-art long-read genetic sequencing to make this important discovery.”

The new research is published in the June issue of Current Biology.

In the past, researchers had to break DNA into short pieces to sequence it. Then they had to put them together, like a jigsaw puzzle, to look at a gene or piece of DNA. However, long-read sequencing allows for sequences of more than 100,000 DNA letters, creating a million-piece puzzle for toddlers.

In addition to the long reads, the researchers validated junctions between integrated bacterial genes and the host fruit fly genome. To determine if the bacterial genes were functional and not just DNA fossils, the researchers sequenced the RNA from fruit flies, looking specifically for copies of RNA made from templates of the inserted bacterial DNA. They showed that the bacterial genes were encoded in RNA and were edited and rearranged into newly modified sequences, indicating that the genetic material is functional.

An analysis of these unique sequences revealed that the bacterial DNA integrated into the fruit fly genome over the past 8,000 years — exclusively within chromosome 4 — increased chromosome size by forming about 20 percent of chromosome 4. The full bacterial genome integration supports a DNA-based rather than an RNA-based integration mechanism.

Dunning Hotopp and colleagues found a complete bacterial genome of the common bacteria Wolbachia transferred to the genome of the fruit fly Drosophila ananassae. They also found nearly a complete second genome and many more with nearly 10 copies of some bacterial genome regions.

“There have always been skeptics about lateral gene transfer, but our research clearly demonstrates for the first time the mechanism of integration of Wolbachia DNA into the genome of this fruit fly,” Dunning Hotopp said.

“This new research shows basic science at its best,” said Dean E. Albert Reece, MD, PhD, MBAalso executive vice president for medical affairs, UM Baltimore, the John Z. and Akiko K. Bowers Distinguished Professor, and dean of UMSOM.“It will contribute to our understanding of evolution and may even prove to help us understand how microbes contribute to human health.”

Wolbachia is an intracellular bacterium that infects numerous species of insects. Wolbachia passes on its genes through the mother via female eggs. Some research has shown that these infections are more mutualistic than parasitic, which gives insects advantages such as resistance to certain viruses.

Sequenced just three years before the human genome, fruit flies have long been used in genomic research because of the abundance of common genetic similarities between flies and humans. In fact, 75 percent of the genes that cause disease in humans are also found in the fruit fly.

Authors of IGS, UMSOM, at the time of writing include: Eric S. Tvedte; Mark Gasser; Laboratory Research Specialist Xuechu Zhao,; Luke J. Tallon, executive scientific director, Maryland Genomics; Lisa Sadzewicz, Executive Director, Maryland Genomics Administration; Laboratory research supervisor Robin E. Bromley; and Matthew Chung; John Mattick, postdoc, and Benjamin C. Sparklin.

Eric S. Tvedte is currently affiliated with NCBI at the National Institutes of Health, Bethesda, MD; Mark Gasser is currently associated with Applied Physics Laboratory, Johns Hopkins University, Laurel, MD; Matthew Chung is currently affiliated with the National Institute for Allergy and Infectious Disease at the National Institutes of Health, Bethesda, MD; and Benjamin C. Sparkin is currently affiliated with AstraZeneca, Rockville, MD.

This work was supported by the National Institute of Allergy and Infectious Diseases grant U19AI110820 and National Institutes of Health grant R01CA206188.

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