This investigation of the fruit fly’s transcriptome—the complete collection of the genome’s RNA—unearthed thousands of new genes, transcripts, and proteins

Scientists have teased another level of information out of the genome. This time, the new insights were developed from studies of the fruit fly’s transcriptome. This knowledge will give pathologists another channel of information that may be useful in developing assays to support more precise diagnosis and therapeutic decisions.

The findings were published in a recent issue of Nature. The study focused on the transcriptome—a complete collection of the genome’s RNA—of the common fruit fly−Drosophila melangogaster.

Why Studies of the Fruit Fly Are Useful

The fruit fly has been used as a genetics model to study human genetics for more than a 100 years. Not only are they easy to care for and work with, but they share 75% of the same genes as humans. Today, the fruit fly genome has emerged as a critical tool tor understanding human biology and disease, by providing an understanding of genes and life processes that are conserved over extensive evolutionary changes.

The research consortium included 41 researchers from 11 universities and institutes that are members of the National Human Genome Research Institute’s Model Organism Encyclopedia of DNA Elements, called modENCODE for short. This project used state-of-the-art gene sequencing to study all of the expressed RNAs produced by a genome in greater detail than ever before accomplished.

RNA Sequenced in Diverse Tissues at Different Stages of Development

RNA was sequenced at different stages of development, in diverse tissues, in cells growing in culture, and in flies stressed by environmental contaminants, stated a IU press release issued by Indiana University Bloomington (IUB).

The modENCODE study revealed that the fruit fly genome is far more complex than previously suspected. These new findings suggest that this also may be true for the genomes of higher animals. Specifically, the researchers found that:

  • a small set of genes in the nervous system is responsible for much of the complexity;
  • long regulatory and antisense RNA (asRNA), a single-stranded RNA complementary to a messenger RNA transcribed within a cell, are prominent during gonadal development;
  • splicing factors, proteins involved in controlling maturation of RNAs, are themselves spliced in complex ways; and,
  • the fruit fly transcriptome undergoes major changes in response to environmental stressors.

How Study of Fruit Fly RNA Benefits Human Genome Research

“The modENCODE work is intended to provide a new baseline for research using Drosophila,” declared Peter Cherbas, Ph.D., an IUB Professor Emeritus of Biology and one of 10 IUB researchers who served as co-authors of the study. “The goal is to provide researchers working on particular processes with much of the detailed background information they would otherwise need to collect for themselves.

Peter Cherbas, Ph.D. (pictured), Professor Emeritus of Biology at Indiana University Bloomington, says that the modENCORE study of the fruit fly’s complete RNA answered a lot of questions about the genome of organisms, but raised even more questions that science will want to answer. (Photo copyright Indiana University Bloomington.)

Peter Cherbas, Ph.D. (pictured), Professor Emeritus of Biology at Indiana University Bloomington, says that the modENCORE study of the fruit fly’s complete RNA answered a lot of questions about the genome of organisms, but raised even more questions that science will want to answer. (Photo copyright Indiana University Bloomington.)

“As usual in science, we’ve answered a number of questions and raised even more,” observed Cherbas. “For example, we identified 1,468 new genes, of which 536 were found to reside in previously uncharacterized gene-free zones.”

“We think these results could influence gene regulation research in all animals,” added Thom Kaufman, Ph.D., IUB Distinguished Professor of Biology who also co-authored the study. “This exhaustive study also identified a number of phenomena previously reported only in mammals, and that alone is really telling about the versatility of Drosophila melanogaster as a model organism. The new work provides a number of new potential uses for this powerful model system,” he stressed

Thom Kaufman, Ph.D. (pictured), Indiana University Bloomington Distinguished Professor of Biology, says that the modENCORE study provides a powerful model for studying gene regulation in all organisms. (Photo copyright Indiana University Bloomington.)

Thom Kaufman, Ph.D. (pictured), Indiana University Bloomington Distinguished Professor of Biology, says that the modENCORE study provides a powerful model for studying gene regulation in all organisms. (Photo copyright Indiana University Bloomington)

Impact of Environmental Stressors on Gene Expression

Both Kaufman and Cherbas cited perturbation experiments that identified genes and transcripts. The new genes were identified after subjecting adult fruit flies to heat and cold shock, then exposing them to heavy metals, caffeine and the herbicide paraquat. Fruit fly larvae were treated with heavy metals, caffeine, ethanol, or the insecticide rotenone.

These environmental stressors generated small changes in the expression level of thousands of genes. One treatment experiment resulted in four newly modeled genes being expressed altogether differently, noted the researchers. Perturbation experiments, in fact, revealed a total of 5,249 transcript models for 811 genes.

In fact, the findings from these perturbation experiments mirror similar findings made following the 2010 British Petroleum Deepwater Horizon oil spill in the Gulf of Mexico., Researchers studying the impact on marsh fishes found that, similar to the fruit flies, these fish responded to chronic hydrocarbon exposure with a number of expressions beyond the heat shock pathway. These expressions included the down regulation of genes encoding eggshell and yolk proteins.

The response overlap between species indicates that the modENCODE consortium may have identified a conserved metazoan [animal] stress response that enhances metabolism and suppresses genes involved in reproduction.

What This Means for Pathologists and Laboratory Professionals

This study is significant for pathologists and medical laboratory professionals because it peels away another layer of information encoded in DNA and RNA. The findings of this study also show how genomic knowledge is moving to the next level in the quest to understand the origins of disease.

—by Patricia Kirk

Related Information:

Study of complete RNA collection of fruit fly uncovers unprecedented complexity

Diversity and dynamics of the Drosophila transcriptome

Scientists at University of Washington Discover a Second Language in DNA, Possibly Giving Pathologists a New Source of Diagnostic Information

New Research Findings Determine that ‘Dark Matter’ DNA Does Useful Work and Opens Door to Develop More Sophisticated Clinical Pathology Laboratory Tests

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