A fruit fly genome is not simply made up of fruit fly DNA, at least for one species of fruit fly. 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 complete genomes of a type of bacteria, making this finding the largest transfer of genetic material from a bacterium to an animal 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 from the bacterium Wolbachia were incorporated into the genome of the fly until 8,000 years ago.
The researchers say their findings show that, unlike Darwin’s finches or Mendel’s peas, genetic variation isn’t always small, incremental and predictable.
Scientist Barbara McClintock first identified “jumping genes” in the 1940s, as those that can move within or transfer to the genomes of other species. However, researchers continue to discover its importance in evolution and health.
Previously, we did not have the technology to unequivocally demonstrate that these genomes within genomes show such extensive lateral gene transfer from bacteria to flies. We used next-generation long-read genetic sequencing to make this important discovery.”
Julie Dunning Hotopp, Professor, Microbiology and Immunology, University of Maryland School of Medicine
The new research has been published in the June issue of current biology.
In the past, researchers had to break DNA into small pieces in order to sequence it. They then needed to put them together, like a puzzle, to look at a gene or section of DNA. However, long-read sequencing allows more than 100,000 DNA letters to be sequenced, turning a million-piece puzzle into one made for young children.
In addition to the long reads, the researchers validated linkages between the integrated bacterial genes and the host fruit fly genome. To determine whether the bacteria’s genes were functional and not just DNA fossils, the researchers sequenced fruit fly RNA specifically looking for RNA copies that were 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 revealed that bacterial DNA integrated into the fruit fly genome over the last 8,000 years, exclusively within chromosome 4, expanding the size of the chromosome by forming about 20 percent of chromosome 4. Integration of the entire bacterial genome supports a DNA-based rather than RNA-based integration mechanism.
Dr. Dunning Hotopp and colleagues found a complete bacterial genome from the common bacterium Wolbachia transferred to the genome of the fruit fly Drosophila ananassae. They also found almost a complete second genome and much more with almost 10 copies of some regions of the bacterial genome.
“There have always been some 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 showcases the best of basic science,” said Dean E. Albert Reece, MD, PhD, MBA, who is also Executive Vice President for Medical Affairs, UM Baltimore, the John Z. and Akiko K. Bowers Distinguished Professor, and Dean of the University of Maryland School of Medicine. “It will add to our understanding of evolution and may even help us understand how microbes contribute to human health.”
Wolbachia is an intracellular bacterium that infects numerous types of insects. Wolbachia pass on their genes maternally through female eggs. Some research has shown that these infections are more mutualistic than parasitic, giving the 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 due to the abundance of common genetic similarities between humans and flies. In fact, 75 percent of the genes that cause human disease can also be found in the fruit fly.
Authors from the University of Maryland School of Medicine’s Genome Sciences Institute, at the time of this writing, include Eric S. Tvedte; Mark Gasser; Xuechu Zhao, laboratory research specialist; Luke J. Tallon, Executive Scientific Director, 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 Johns Hopkins University Applied Physics Laboratory, Laurel, MD; Matthew Chung is currently affiliated with the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, Bethesda, MD; and Benjamin C. Sparkin is currently affiliated with AstraZeneca, Rockville, MD.
This work was supported by grant U19AI110820 from the National Institute of Allergy and Infectious Diseases and grant R01CA206188 from the National Institutes of Health.