Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

When the cell’s two genomes collide

06.02.2013
Plant and animal cells contain two genomes: one in the nucleus and one in the mitochondria. When mutations occur in each, they can become incompatible, leading to disease. To increase understanding of such illnesses, scientists at Brown University and Indiana University have traced one example in fruit flies down to the individual errant nucleotides and the mechanism by which the flies become sick.

Diseases from a mutation in one genome are complicated enough, but some illnesses arise from errant interactions between two genomes: the DNA in the nucleus and in the mitochondria. Scientists want to know more about how such genomic disconnects cause disease. In a step in that direction, scientists at Brown University and Indiana University have traced one such incompatibility in fruit flies down to the level of individual nucleotide mutations and describe how the genetic double whammy makes the flies sick.


Understanding a genetic double whammy
Bright areas surrounding darker oval nuclei denote the location of mitochondria in the stained cells of fruit fly ovaries. Brown and Indiana researchers have traced the genetic and biochemical roots of a disease that arose in flies from an incompatibility between the nuclear and mitochondrial genomes. Credit: Rand lab/Brown University

“This has relevance to human disease but it’s also relevant to all organisms because these two genomes are in all animals and all plants,” said David Rand professor of biology at Brown and senior author of the study in PLoS Genetics. “There are a lot of metabolic diseases that are mitochondrial in origin and they have peculiar genetic tracking — a two-part system needs to be considered.”

Five years ago at Brown, Rand and two postdoctoral researchers — Colin Meiklejohn, of Brown and Indiana University, and Kristi Montooth, now an assistant professor at Indiana University — began searching for an example in the convenient testbed of fruit flies. They started mixing and matching mitochondrial and nuclear genomes from different strains and species of flies that carried natural mutations produced during evolution to observe what conflicts might arise. They found that when they placed the “simw 501” mitochondrial DNA from Drosophila simulans flies into Drosophila melanogaster flies with “Oregon R” nuclear DNA, bad things happened.

The flies with this combination lived but had an array of problems. Their most noticeable flaw was that whisker-like bristles on their backs were only half the length of those in normal flies. The flies also had developmental delays, reproduced less effectively, and tired more quickly, which makes sense because the mitochondria is the cell’s power plant.

Once the team, including lead author Meiklejohn, had a bona fide mitochondrial-nuclear incompatibility to study, they could then begin looking for exactly where the problem lay and how it was causing disease. In the paper, they describe the genetic and biochemical experiments they conducted to find out.

Brown graduate student Marissa Holmbeck, the paper’s second author, measured the productivity of several enzymes in the mitochondria’s power generation process. Two enzymes that are derived entirely from nuclear genes ran just as well in the sick flies as in healthy ones, but three enzymes that are jointly managed by mitochondrial and nuclear genes lagged behind in activity.

“The different complexes that are jointly encoded by the mitochondrial and nuclear subunits, those are the ones where we are seeing the defect in activity,” Holmbeck said.

Each mutation alone, in fact, does little or no harm to flies. It is only when both are present that the flies fall ill.

Meanwhile, Meiklejohn and Montooth tracked those mutations to just two altered nucleotide letters — one in each genome. In the mitochondrial genome, a G to U mutation in an RNA suggested a problem with protein production inside the mitochondria. This was confirmed when they discovered an A to V mutation in the nuclear protein that adds an amino acid to this same mitochondrial RNA.

The biochemical and genetic evidence pointed to flaws in how fast the mitochondria of the sick flies could produce proteins needed to promote growth.

“The specifics of this paper are tracking that down to the individual nucleotide,” Rand said, “But the more general lesson is that this coevolution of mitochondrial and nuclear genes has been going on for millions of years in millions of organisms and is going on in human populations today.”

In human beings, a well-known mitochondrial disease, for example, is an aversion to exercise that is due to a mutation in the same mitochondrial RNA gene the team studied in fruit flies.

Rand and his group are now conducting new experiments to trace more mito-nuclear incompatibilities within a single species to their genetic and biochemical roots.

“This paper provided proof of principle that we can identify these things and map them to their nucleotides,” Rand said. “We want to ask how common is this and can we find other sources of this kind of breakdown in mito-nuclear crosstalk underlying disease.”

In addition to Rand, Montooth, Meiklejohn, and Holmbeck, other authors on the paper are Dawn Abt of Brown and Mohammad Siddiq of Indiana.

The National Institutes of Health funded the research with several grants, including GM072399, F31AG040925, R01GM067862, R01AG027849, and GM076812. The National Science Foundation funded the research with grant DEB-0839348. Support also came from Indiana University.

Editors: Brown University has a fiber link television studio available for domestic and international live and taped interviews, and maintains an ISDN line for radio interviews. For more information, call (401) 863-2476.

David Orenstein | EurekAlert!
Further information:
http://www.brown.edu

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>