A fruit fly genome doesn’t just consist of fruit fly DNA – at least for one fruit fly species. New research from the Institute for Genome Sciences (IGS) at the University of Maryland School of Medicine (UMSOM) shows that one species of fruit fly contains whole genomes of a type of bacteria, making this find the largest transfer of genetic material from bacteria to animal ever discovers. The new research also sheds light on how this happens.
The IGS researchers, led by Julie Dunning Hotopp, PhD, Professor of Microbiology and Immunology at UMSOM and IGS, used novel genetic long-read sequencing technology to show how genes from the bacterium Wolbachia incorporated themselves 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, 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 had not previously had the technology to unequivocally demonstrate these genomes-within-genomes that show such extensive lateral gene transfer from the bacterium to the fly. We used state-of-the-art 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 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 a 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 has been integrated into the fruit fly genome over the past 8,000 years -; only within chromosome 4; increasing chromosome size by forming about 20 percent of chromosome 4. Integration of the whole bacterial genome supports a DNA-based rather than an RNA-based mechanism of integration.
dr. Dunning Hotopp and colleagues found a complete bacterial genome of the common bacterium 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,” 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 for Medical Affairs, UM Baltimore, the John Z. and Akiko K. Bowers Distinguished Professor, and Dean, University of Maryland School of Medicine. “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 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, 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 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 National Institute of Allergy and Infectious Diseases Grant U19AI110820 and National Institutes of Health Grant R01CA206188.
University of Maryland School of Medicine
Tvedte ES, et al. (2022) Accumulation of endosymbiont genomes in an insect autosome followed by endosymbiont replacement. Current Biology. doi.org/10.1016/j.cub.2022.05.024.