Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Redundant genetic instructions in 'junk DNA' support healthy development

19.07.2010
Seemingly redundant portions of the fruit fly genome may not be so redundant after all

New findings from a Princeton-led team of researchers suggest that repeated instructional regions in the flies' DNA may contribute to normal development under less-than-ideal growth conditions by making sure that genes are turned on and off at the appropriate times. If similar regions are found in humans, they may hold important clues to understanding developmental disorders.

The research results, published in the July 22 issue of the journal Nature, add to the growing body of evidence that so-called "junk DNA" is anything but rubbish. The term "junk DNA" is commonly used to describe the portion of the genome that doesn't contain genes, which are pieces of DNA that code for the production of proteins and other molecules that have specific functions. The noncoding region is often surprisingly large; in humans, some 98 percent of the genome merits "junk" status. But according to David Stern, a Princeton professor in the Department of Ecology and Evolutionary Biology, scientists increasingly believe "junk DNA" is crucial for turning the information encoded in genes into useful products.

"Over the past 10 to 20 years, research has shown that instructional regions outside the protein-coding region are important for regulating when genes are turned on and off," said Stern, the senior scientist on the paper. "Now we're finding that additional copies of these genetic instructions are important for maintaining stable gene function even in a variable environment, so that genes produce the right output for organisms to develop normally."

Stern, along with Nicolás Frankel, a postdoctoral research fellow at Princeton, and their collaborators focused their attention on instructional regions called enhancers. These regions play an important role in the process by which information encoded in genes is used to direct the synthesis of the proteins that make an organism what it is -- be it a fly, a mouse or a human.

"To interpret and fully understand the genome, we need to think of it from an ecological and evolutionary perspective," Stern said. "Its purpose is to produce a healthy organism in a variable environment, so a good portion of it has evolved to deal with contingencies that organisms will experience in the real world."

When enhancers were first discovered, scientists believed that they always were located in close proximity to the target genes that they regulate. Distances in DNA are measured in base pairs, which are the building blocks that make up the DNA molecule (for comparison, the entire fruit fly genome contains about 130 million base pairs, while the human genome has more than 3 billion). Until recently, enhancers were thought always to exist within about 1,000 base pairs from their target genes.

But in 2008, the University of California-Berkeley's Michael Levine reported the discovery of secondary enhancers for a particular fruit fly gene that were located much farther away from the target genes and from the previously discovered enhancers that were located adjacent to the gene.

Levine's team called the apparently redundant copies in distant genetic realms "shadow enhancers" and hypothesized that they might serve to make sure that genes are expressed normally, even if development is disturbed. Factors that might induce developmental disturbances include environmental conditions, such as extreme temperatures, and internal factors, such as mutations in other genes.

Stern and his team put Levine's hypothesis to the test by studying a fruit fly gene that codes for the production of tiny hair-like projections on the insect's body, which are called trichomes. The gene, known as shavenbaby, takes its name from the fact that flies with a mutated copy of the gene are nearly hairless. Stern previously led a research effort that identified three primary enhancers for shavenbaby. In the new research, his team discovered two shadow enhancers for shavenbaby, located more than 50,000 base pairs away from the gene.

In their experiments, the researchers deleted these two shadow enhancers, leaving the primary enhancers in place, and observed developing fly embryos under a range of temperature conditions. At optimal temperatures for fruit fly development -- around 25 degrees Celsius, or a comfortable 77 degrees Fahrenheit -- the embryos without shadow enhancers had only very slight defects in their trichomes. But the results were very different when the researchers observed embryos that developed at temperatures close to the extremes at which developing fruit flies can survive -- 17 degrees Celsius, or 63 degrees Fahrenheit, on the low end and 32 degrees Celsius, or 90 degrees Fahrenheit, at the upper limit. These flies without shadow enhancers developed with severe deficiencies in the number of trichomes produced.

"These results indicate that the genetic instructions that seemed dependable at optimal temperatures were just not up to the task in other conditions," Stern said.

To test internal factors affecting developmental deficiencies, the team also investigated what would happen if the secondary enhancers for the shavenbaby gene were removed from fruit fly embryos that had a mutation in another gene involved in trichome development. They found that trichome formation in the mutants was significantly more impaired when the shadow enhancers were absent. Along with the findings of the temperature experiment, the results support the hypothesis that shadow enhancers make developing embryos more robust to both environmental and genetic variation.

The work has important implications for the design of future experiments, which are often conducted in the lab under ideal conditions for the growth of the study organisms. While conducive for proper development, these experimental set-ups may mask the significant role shadow enhancers play to ensure normal development. Future studies of development could explore less optimal settings.

"Backup regulatory DNAs, also called shadow enhancers, ensure the reliable activities of essential genes such as shavenbaby even under adverse conditions, such as increases in temperature," Levine said. "If Dr. Stern and his associates had not examined the activities of shavenbaby under such conditions, then the shadow enhancers might have been missed since they are not needed when fruit flies are grown at optimal culturing conditions in the laboratory."

To date, shadow enhancers have been discovered for numerous genes in fruit flies and mice. Many scientists, including Stern and Levine, believe similarly redundant instructional regions are pervasive in the human genome. If this is found to be true, it could have important implications for understanding a wide range of developmental disorders and explaining why some people with certain genetic mutations develop a given condition while others do not. The presence of shadow enhancers could be one of the determining factors in this "genetic lottery."

In addition to Frankel and Stern, Princeton researchers on the team included senior research specialist Shu Wang in ecology and evolutionary biology and Diego Vargas, a member of Princeton's undergraduate class of 2011. The team also included biologist Gregory Davis of Bryn Mawr College and François Payre of the University of Toulouse and Centre National de la Recherche Scientifique in France. The research was supported by the Howard Hughes Medical Institute, the National Institutes of Health, the National Science Foundation and the Pew Charitable Trusts.

Kitta MacPherson | EurekAlert!
Further information:
http://www.princeton.edu

More articles from Life Sciences:

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

nachricht CWRU researchers find a chemical solution to shrink digital data storage
22.06.2017 | Case Western Reserve University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

A new technique isolates neuronal activity during memory consolidation

22.06.2017 | Life Sciences

Plant inspiration could lead to flexible electronics

22.06.2017 | Materials Sciences

A rhodium-based catalyst for making organosilicon using less precious metal

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>