Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Genetic Material Hitchhiking in Our Cells May Shape Physical Traits

Published: Wednesday, May 14, 2014
Last Updated: Wednesday, May 14, 2014
Bookmark and Share
Explaining the connection between genotype and phenotype must also consider genetic material that doesn’t come from an organism’s chromosomes at all.

In 2003, when the human genome had been sequenced, many people expected a welter of new therapies to follow, as biologists identified the genes associated with particular diseases.

But the process that translates genes into proteins turned out to be much more involved than anticipated. Other elements — proteins, snippets of RNA, regions of the genome that act as binding sites, and chemical groups that attach to DNA — also regulate protein production, complicating the relationship between an organism’s genetic blueprint, or genotype, and its physical characteristics, or phenotype.

In the latest issue of the Proceedings of the National Academy of Sciences, researchers from MIT and the Whitehead Institute for Biomedical Research argue that biologists trying to explain the connection between genotype and phenotype need to consider yet another factor: genetic material that doesn’t come from an organism’s chromosomes at all.

Through a combination of clever lab experiments and quantitative analysis, the researchers showed that the consequences of deleting genes in yeast cells can’t be explained without the additional consideration of nonchromoomal genetic material — in particular, from the intracellular bodies known as mitochondria and from viruses that can linger in dividing cells.

“This reinforces the idea that when considering human genetics, we need to consider lots of different factors,” says David Gifford, a professor of computer science and engineering at MIT, who led the quantitative analysis. “We need to understand to what extent viruses can be passed from parent to offspring, as well as understanding the spectrum of mitochondria that are present in humans and their potential interactions with chromosomal mutations.”

Benchtop conundrum

The new work grew out of a fairly standard attempt to analyze the role of a particular group of yeast genes, Gifford explains, by comparing the growth rates of yeast colonies in which these genes had or had not been deleted. But the growth of the colonies with deletions was all over the map: Sometimes it was as robust as in the normal yeast cells, sometimes it was dramatically slower, and often it was in between.

“We couldn’t reproduce many of our findings and found out that as experiments were progressing, this double-stranded RNA virus was being lost in particular strains, although it was having a large influence when it was present,” Gifford says. “We then hypothesized that if this virus was important, it was conceivable that other nonchromosomal genetic elements could be important, and that’s when we started looking at the mitochondria. And our collaborators at the Whitehead Institute designed this very clever way of swapping mitochondria between yeast strains so we could isolate and examine exactly what effect the mitochondria were having.”

Mitochondria are an evolutionary peculiarity. Frequently referred to as the “power plant of the cell” because they produce the chemical fuel adenosine triphosphate, or ATP, they are essential components of almost all plant, animal, and fungus cells. But they have their own genomes, which are distinct from those of their host cells. The leading theory about their origin is that they were originally bacteria that developed a symbiotic relationship with early life forms.

Asserting control

Gerald Fink, the American Cancer Society Professor of Genetics at MIT and a member of the Whitehead Institute, and two researchers in his group — Lindsey Dollard and Anna Symbor-Nagrabska — removed the mitochondria from one of the yeast cells they were studying and allowed it to mate with a cell from a different yeast strain. But they prevented the cells’ nuclei — the repositories of their genetic material — from fusing. Then they forced the new, two-nucleus cell to divide, creating a new strain in which the nucleus of one yeast strain was combined with the mitochondria of the other.

In this way, for each of the genetic deletions the researchers studied, they had strains in which each nuclear state — gene deleted, or left intact — was combined with each of several different types of mitochondria. For each of those strains, they also created variations that were and were not infected with the virus.

Compounded influences

That provided Gifford and his student Matthew Edwards with reliable data, but they still had to make sense of it. Gene deletion alone seemed to explain about 40 percent of the variance they saw in yeast colonies’ growth rates. Gene deletion combined with a blunt categorization of strains according to their nonchromosomal material explained the other 60 percent.

But Gifford and Edwards built a more detailed mathematical model that posited a nonlinearinteraction between the virus and particular strains of mitochondria. That model explained more than 90 percent of the variation they saw — not only in colonies with deleted genes, but in the naturally occurring yeast cells as well.

“You might think that the effect of the chromosomal modification and the effect, for example, of the virus were both important but independent,” Gifford says. “What we found is that they weren’t independent. They were synergistic.”

“At a very high level and at a very conceptual level, what they’re showing is that we should also be looking for heritability and variation in phenotype in regions that are not in the chromosomal DNA,” says Eran Segal, a professor of applied mathematics at the Weizmann Institute in Israel whose group does computational biology. “There’s anecdotal evidence that we’ll see similar things in humans.”

Biologists attempting to fill gaps in our understanding of heritability have offered “plausible explanations, like rare variants and combinations that from a statistical-power point of view are hard to analyze,” Segal says. “Some of the missing heritability is definitely in there.” But the MIT researchers’ paper, he says, “highlights that there may be simpler — simpler in the sense that we can more easily access it — heritability that we can explain maybe by also looking at the nonchromosomal genetic material that human cells carry. With fairly easy techniques, we can access that information, and I think that researchers in the field would be wise to begin to look at it.”


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More Than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Friday, July 31, 2015
Firms “Under-invest” in Long-Term Cancer Research
Tweaks to the R&D pipeline could create new drugs and greater social benefit.
Thursday, July 30, 2015
Nanoparticles Can Clean Up Environmental Pollutants
Researchers have found that nanomaterials and UV light can “trap” chemicals for easy removal from soil and water.
Thursday, July 23, 2015
Bacterial Computing
The “friendly” bacteria inside our digestive systems are being given an upgrade, which may one day allow them to be programmed to detect and ultimately treat diseases such as colon cancer and immune disorders.
Monday, July 13, 2015
Researchers Develop Genetic Tools to Engineer Common Gut Bacterium
Researchers from the Massachusetts Institute of Technology have developed genetic parts that can be combined to program the commensal gut bacterium Bacteroides thetaiotaomicron.
Friday, July 10, 2015
Chemists Design a Quantum-Dot Spectrometer
New instrument is small enough to function within a smartphone, enabling portable light analysis.
Friday, July 03, 2015
Longstanding Problem Put to Rest
Proof that a 40-year-old algorithm for comparing genomes is the best possible will come as a relief to computer scientists.
Thursday, June 11, 2015
Tough biogel structures produced by 3-D printing
Researchers have developed a new way of making tough — but soft and wet — bio-compatible materials, called “hydrogels,” into complex and intricately patterned shapes.
Wednesday, June 03, 2015
Diagnosing Cancer with Help from Bacteria
Engineered probiotics can detect tumors in the liver.
Friday, May 29, 2015
Master Gene Regulator Could Be New Target For Schizophrenia Treatment
Researchers at MIT’s Picower Institute for Learning and Memory have identified a master genetic regulator that could account for faulty brain functions that contribute to schizophrenia.
Wednesday, May 27, 2015
Freshly Squeezed Vaccines
Microfluidic cell-squeezing device opens new possibilities for cell-based vaccines.
Saturday, May 23, 2015
Designing Better Medical Implants
A team of MIT researchers have discovered a novel method for reducing the typical immune system rejection response when implanting biomedical devices into the body.
Wednesday, May 20, 2015
Researchers Identify New Target For Anti-Malaria Drugs
Manipulating the permeability of a type of vacuole could help defeat malarial parasites.
Thursday, May 14, 2015
Faster, Smaller, More Informative
Device can measure the distribution of tiny particles as they flow through a microfluidic channel.
Thursday, May 14, 2015
How To Identify Drugs That Work Best For Each Patient
Implantable device could allow doctors to test cancer drugs in patients before prescribing chemotherapy.
Monday, April 27, 2015
Scientific News
Liquid Biopsies: Utilization of Circulating Biomarkers for Minimally Invasive Diagnostics Development
Market Trends in Biofluid-based Liquid Biopsies: Deploying Circulating Biomarkers in the Clinic. Enal Razvi, Ph.D., Managing Director, Select Biosciences, Inc.
Self-Assembling, Biomimetic Membranes May Aid Water Filtration
A synthetic membrane that self assembles and is easily produced may lead to better gas separation, water purification, drug delivery and DNA recognition, according to an international team of researchers.
Researchers Discover Immune System’s 'Trojan Horse'
Oxford University researchers have found that human cells use viruses as Trojan horses, transporting a messenger that encourages the immune system to fight the very virus that carries it.
Crystal Clear Images Uncover Secrets of Hormone Receptors
NIH researchers gain better understanding of how neuropeptide hormones trigger chemical reactions in cells.
How Cholesterol Leads to Clogged Arteries
A new study shows that when immune cells called neutrophils are exposed to cholesterol crystals, they release large extracellular web-like structures that trigger the production of inflammatory molecules linked to artherosclerosis.
Genetic Tug of War
Researchers have reported on a version of genetic parental control in mice that is more targeted, and subtle than canonical imprinting.
Ultrafast DNA Diagnostics
New technology developed by UC Berkeley bioengineers promises to make a workhorse lab tool cheaper, more portable and many times faster by accelerating the heating and cooling of genetic samples with the switch of a light.
Researchers Discover New Type of Mycovirus
Virus infects the fungus Aspergillus fumigatus, which can cause the human disease aspergillosis.
Error Correction Mechanism in Cell Division
Cell biologists have reported an advance in understanding the workings of an error correction mechanism that helps cells detect and correct mistakes in cell division early enough to prevent chromosome mis-segregation and aneuploidy, that is, having too many or too few chromosomes.
How to Become a Follicular T Helper Cell
Uncovering the signals that govern the fate of T helper cells is a big step toward improved vaccine design.
Scroll Up
Scroll Down

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!