A fruit fly genome is not just made up of fruit fly DNA – at least for a fruit fly species. New research from the Institute for Genome Sciences (IGS) at the University of Maryland School of Medicine (UMSOM) shows that a species of fruit fly contains entire genomes of a type of bacteria, this making it the largest transfer of genetic material from bacteria to animals ever. discovered. The new research also sheds light on how this happens.

IGS researchers, led by Julie Dunning Hotopp, PhD, professor of microbiology and immunology at UMSOM and IGS, used new long-read gene sequencing technology to show how genes in Wolbachia bacteria incorporated into the fly 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, gradual and predictable.

Scientist Barbara McClintock first identified “jumping genes” in the 1940s, as those that can move or transfer into the genomes of other species. However, researchers continue to discover their importance in evolution and health.

“We did not previously have the technology to unequivocally demonstrate these genomes within genomes showing such extensive lateral gene transfer from bacteria to fly,” explained Dr. Dunning Hotopp. “We used state-of-the-art long-read gene sequencing to make this important discovery.”

The new research was published in the June issue of Current biology.

In the past, researchers had to break DNA into small pieces in order to sequence it. Then they had to put them together, like a puzzle, to examine a gene or a section of DNA. Long-read sequencing, however, allows for sequences of over 100,000 letters of DNA, turning a million-piece puzzle into one designed for toddlers.

In addition to the long reads, the researchers validated the junctions between the integrated bacteria genes and the host fruit fly genome. To determine if the bacteria’s genes were functional and not just DNA fossils, the researchers sequenced RNA from fruit flies looking specifically for RNA copies created from templates of the inserted bacterial DNA. They showed that the bacteria’s 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 has revealed that the bacteria’s DNA has integrated into the fruit fly genome over the past 8,000 years – exclusively in chromosome 4 – increasing the size of the chromosome by constituting about 20% of chromosome 4. The integration of the whole bacterial genome supports a DNA-based rather than an RNA-based integration mechanism.

Dr. Dunning Hotopp and his colleagues discovered a complete bacterial genome of the common bacterium Wolbachia transferred into the genome of the fruit fly Drosophila ananassae. They also found almost a complete second genome and much more with almost 10 copies of certain regions of the bacterial genome.

“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,” said Dr Dunning. Hotopp.

“This new research shows basic science at its best,” said Dean E. Albert Reece, MD, PhD, MBA, who is also executive vice president of medical affairs, UM Baltimore, John Z. Professor Emeritus and Akiko K Bowers, and Dean of the University of Maryland Medical School. “It will contribute to our understanding of evolution and may even help us understand how microbes contribute to human health.”

Wolbachia is an intracellular bacterium that infects many types of insects. Wolbachia transmits its genes maternally through female eggs. Some research has shown that these infections are more mutualistic than parasitic, conferring advantages on insects, such as resistance to certain viruses.

Sequenced just three years before the human genome, fruit flies have long been used in genomics research due to the abundance of common fly-human genetic similarities. In fact, 75% of the genes responsible for human diseases are also found in the fruit fly.

Authors from the Institute of Genome Sciences, University of Maryland School of Medicine, at the time of writing, include Eric S. Tvedte; Mark Gasser; Xuechu Zhao, laboratory research specialist; Luke J. Tallon, Chief Scientific Officer, Maryland Genomics; Lisa Sadzewicz, Executive Director, Maryland Genomics Administration; Robin E. Bromley, laboratory research supervisor; 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 affiliated with the Applied Physics Laboratory, Johns Hopkins University, Laurel, MD; Matthew Chung is currently affiliated with the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; and Benjamin C. Sparkin is currently affiliated with AstraZeneca, Rockville, MD.

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