Whole-genome transfer raises questions about evolution, sequencing
Scientists at the University of Rochester and the J. Craig Venter Institute have discovered a copy of the entire genome of a bacterial parasite residing inside the genome of its host species.
The finding, reported in today’s Science, suggests that lateral gene transfer—the movement of genes between unrelated species—may happen much more frequently between bacteria and multicellular organisms than scientists previously believed, posing dramatic implications for evolution.
Such large-scale heritable gene transfers may allow species to acquire new genes and functions extremely quickly, says Jack Werren, a principle investigator of the study.
Wolbachia in yellow with host cells in red.
The results also have serious repercussions for genome-sequencing projects. Bacterial DNA is routinely discarded when scientists are assembling invertebrate genomes, yet these genes may very well be part of the organism’s genome, and might even be responsible for functioning traits.
“This study establishes the widespread occurrence and high frequency of a process that we would have dismissed as science fiction until just a few years ago,” says W. Ford Doolittle, Canada Research Chair in Comparative Microbial Genomics at Dalhousie University, who is not connected to the study. “This is stunning evidence for increased frequency of gene transfer.”
Fruit fly ovaries showing wolbachia infection within.
“It didn’t seem possible at first,” says Werren, professor of biology at the University of Rochester and a world-leading authority on the parasite, called Wolbachia. “This parasite has implanted itself inside the cells of 70 percent of the world’s invertebrates, coevolving with them. And now, we’ve found at least one species where the parasite’s entire or nearly entire genome has been absorbed and integrated into the host’s. The host’s genes actually hold the coding information for a completely separate species.”
Wolbachia may be the most prolific parasite in the world—a “pandemic,” as Werren calls it. The bacterium invades a member of a species, most often an insect, and eventually makes its way into the host’s eggs or sperm. Once there, the Wolbachia is ensured passage to the next generation of its host, and any genetic exchanges between it and the host also are much more likely to be passed on.
Since Wolbachia typically live within the reproductive organs of their hosts, Werren reasoned that gene exchanges between the two would frequently pass on to subsequent generations. Based on this and an earlier discovery of a Wolbachia gene in a beetle by the Fukatsu team at the University of Tokyo, Japan, the researchers in Werren’s lab and collaborators at J. Craig Venter Institute (JCVI) decided to systematically screen invertebrates. Julie Dunning-Hotopp at JCVI found evidence that some of the Wolbachia genes seemed to be fused to the genes of the fruitfly, Drosophila ananassae, as if they were part of the same genome.
Michael Clark, a research associate at Rochester then brought a colony of ananassae into Werren’s lab to look into the mystery. To isolate the fly’s genome from the parasite’s, Clark fed the flies a simple antibiotic, killing the Wolbachia. To confirm the ananassae flies were indeed cured of the wolbachia, Clark tested a few samples of DNA for the presence of several Wolbachia genes.
To his dismay, he found them.
“For several months, I thought I was just failing,” says Clark. “I kept administering antibiotics, but every single Wolbachia gene I tested for was still there. I started thinking maybe the strain had grown antibiotic resistance. After months of this I finally went back and looked at the tissue again, and there was no Wolbachia there at all.”
Clark had cured the fly of the parasite, but a copy of the parasite’s genome was still present in the fly’s genome. Clark was able to see that Wolbachia genes were present on the second chromosome of the insect.
Clark confirmed that the Wolbachia genes are inherited like “normal” insect genes in the chromosomes, and Dunning-Hotopp showed that some of the genes are “transcribed” in uninfected flies, meaning that copies of the gene sequence are made in cells that could be used to make Wolbachia proteins.
Werren doesn’t believe that the Wolbachia “intentionally” insert their genes into the hosts. Rather, it is a consequence of cells routinely repairing their damaged DNA. As cells go about their regular business, they can accidentally absorb bits of DNA into their nuclei, often sewing those foreign genes into their own DNA. But integrating an entire genome was definitely an unexpected find.
Werren and Clark are now looking further into the huge insert found in the fruitfly, and whether it is providing a benefit. “The chance that a chunk of DNA of this magnitude is totally neutral, I think, is pretty small, so the implication is that it has imparted of some selective advantage to the host,” says Werren. “The question is, are these foreign genes providing new functions for the host” This is something we need to figure out.”
Evolutionary biologists will certainly take note of this discovery, but scientists conducting genome-sequencing projects around the world also may have to readjust their thinking.
Before this study, geneticists knew of examples where genes from a parasite had crossed into the host, but such an event was considered a rare anomaly except in very simple organisms. Bacterial DNA is very conspicuous in its structure, so if scientists sequencing a nematode genome, for example, come across bacterial DNA, they would likely discard it, reasonably assuming that it was merely contamination—perhaps a bit of bacteria in the gut of the animal, or on its skin.
But those genes may not be contamination. They may very well be in the host’s own genome. This is exactly what happened with the original sequencing of the genome of the anannassae fruitfly—the huge Wolbachia insert was discarded from the final assembly, despite the fact that it is part of the fly’s genome.
In the early days of the Human Genome Project, some studies appeared to show bacterial DNA residing in our own genome, but those were shown indeed to be caused by contamination. Wolbachia is not known to infect any vertebrates such as humans.
“Such transfers have happened before in the distant past” notes Werren. “In our very own cells and those of nearly all plants and animals are mitochondria, special structures responsible for generating most of our cells’ supply of chemical energy. These were once bacteria that lived inside cells, much like Wolbachia does today. Mitochondria still retain their own, albeit tiny, DNA, and most of the genes moved into the nucleus in the very distant past. Like wolbachia, they have passively exchanged DNA with their host cells. It’s possible wolbachia may follow in the path of mitochondria, eventually becoming a necessary and useful part of a cell.
“In a way, wolbachia could be the next mitochondria,” says Werren. “A hundred million years from now, everyone may have a wolbachia organelle.”
“Well, not us,” he laughs. “We’ll be long gone, but wolbachia will still be around.”
This research was funded by the National Science Foundation.
Scientists have only recently begun to speculate that what’s referred to as “junk” DNA – the 96 percent of the human genome that doesn’t encode for proteins and previously seemed to have no useful purpose – is present in the genome for an important reason. But it wasn’t clear what the reason was. Now, researchers at the University of California, San Diego (UCSD) School of Medicine have discovered one important function of so-called junk DNA.
Genes, which make up about four percent of the genome, encode for proteins, “the building blocks of life.” An international collaboration of scientists led by Michael G. Rosenfeld, M.D., Howard Hughes Medical Investigator and UCSD professor of medicine, found that some of the remaining 96 percent of genomic material might be important in the formation of boundaries that help properly organize these building blocks. Their work will be published in the July 13 issue of the journal Science.
“Some of the ‘junk’ DNA might be considered ‘punctuation marks’ – commas and periods that help make sense of the coding portion of the genome,” said first author Victoria Lunyak, Ph.D., assistant research scientist at UCSD.
In mice, as in humans, only about 4 percent of the genome encodes for protein function; the remainder, or “junk” DNA, represents repetitive and non-coding sequences. The research team studied a repeated genomic sequence called SINE B2, which is located on the growth hormone gene locus, the gene related to the aging process and longevity. The scientists were surprised to find that SINE B2 sequence is critical to formation of the functional domain boundaries for this locus.
Functional domains are stretches of DNA within the genome that contain all the regulatory signals and other information necessary to activate or repress a particular gene. Each domain is an entity unto itself that is defined, or bracketed, by a boundary, much as words in a sentence are bracketed by punctuation marks. The researchers’ data suggest that repeated genomic sequences might be a widely used strategy used in mammals to organize functional domains.
“Without boundary elements, the coding portion of the genome is like a long, run-on sequence of words without punctuation,” said Rosenfeld.
Decoding the information written in “junk” DNA could open new areas of medical research, particularly in the area of gene therapy. Scientists may find that transferring encoding genes into a patient, without also transferring the surrounding genomic sequences which give structure or meaning to these genes, would render gene therapy ineffective.
Contributors to the paper include Lluis Montoliu, Rosa Roy and Angel Garcia-Díaz of the Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología in Madrid, Spain; Christopher K. Glass, M.D., Ph.D., UCSD Department of Cellular and Molecular Medicine; Esperanza Núñez, Gratien G. Prefontaine, Bong-Gun Ju, Kenneth A. Ohgi, Kasey Hutt, Xiaoyan Zhu and Yun Yung, Howard Hughes Medical Institute, Department of Molecular Medicine, UCSD School of Medicine; and Thorsten Cramer, Division of Endocrinology, UCSD Department of Medicine.
The research was funded in part by the Howard Hughes Medical Institute and the National Institutes of Health.
Contact: Debra Kain
University of California – San Diego
Contact: Erin Doonan
In the vast majority of Parkinson’s disease (PD) patients, the disorder arises not because of a genetic defect, but because some external insult triggers the death of dopamine-producing neurons. Now, researchers have reported progress in understanding the mechanism underlying that death, which they say suggests a new treatment pathway.
In both mice and human patients, the researchers have found evidence that neurons die because of a crippling of a particular protective enzyme that eliminates potentially damaging “reactive oxygen species” normally generated in the cell’s power plants, called mitochondria.
David Park, of the Ottawa Health Research Institute, and colleagues published their findings in the July 5, 2007 issue of the journal Neuron, published by Cell Press.
The researchers studied the mechanism of PD using a mouse model of the disease, in which a mitochondria-affecting toxin called MPTP is used to produce Parkinson’s-like brain pathology. In earlier studies, they had found that MPTP activates protein-snipping enzymes called calpains in mitochondria. They also found evidence that calpains, in turn, activate a cellular switch called Cdk5. The question, however, was how this abnormal activation ultimately kills neurons.
In their new studies, the researchers analyzed neurons to determine that Cdk5 regulates yet another enzyme called Prx2. This enzyme is known as a peroxidase and acts to render harmless the chemically active reactive oxygen species that are produced inside mitochondria in the process of generating energy for the cell.
Specifically, the researchers found that treating neurons with MPTP activates Cdk5 to switch off Prx2. What’s more, they found that activating Prx2 in MPTP-treated mice prevented the loss of dopamine-producing neurons. And they experimentally demonstrated that the action of Cdk5 on Prx2 “plays a pivotal role” in the neuronal damage from MPTP.
Importantly, the researchers discovered evidence that the loss of Prx2 activity also plays a role in human PD. They found reduced Prx2 activity in brain tissue from PD patients.
“These findings provide a mechanistic link of how a mitochondrial damaging agent, through calpain-mediated Cdk5 activation and downregulation of an important antioxidant enzyme, can increase oxidative load, leading ultimately to death,” concluded the scientists.
“Taken together, our findings suggest that strategies to modulate Prx2 activity serve as beneficial targets for treatment of PD,” they concluded. “This is of particular importance since Cdk5 is thought to have normal beneficial roles in neurons and modulating a relevant downstream target rather than Cdk5 directly may be a better therapeutic strategy with regard to this pathway.”
The researchers include Dianbo Qu, Juliet Rashidian, Matthew P. Mount, Hossein Aleyasin, Mohammad Parsanejad, Arman Lira, Emdadul Haque, Yi Zhang, Steve Callaghan, Mireille Daigle, Maxime W.C. Rousseaux, Ruth S. Slack, Paul R. Albert, John M. Woulfe, and David S. Park of University of Ottawa, Ottawa, Ontario, Canada; Inez Vincent of University of British Columbia, Vancouver, British Columbia, Canada.
This work was partially supported by the Parkinson’s Disease Foundation and the Parkinson’s Society of Canada (D.Q.) and the Heart and Stroke Foundation (J.R., H.A.) and by funds from the Canadian Institutes of Health Research, the Parkinson’s Society Canada, the Parkinson’s Disease Foundation, the Parkinson’s Research Consortium, the US army, and the Heart and Stroke Foundation of Ontario (D.S.P.).
Qu et al.: “Role of Cdk5-Mediated Phosphorylation of Prx2 in MPTP Toxicity and Parkinson’s Disease.” Publishing in Neuron 55, 37–52, July 5, 2007. DOI 10.1016/j.neuron.2007.05.033. http://www.neuron.org.
Contact: Emily Butler
Kennedy Krieger Institute
Researchers at the Kennedy Krieger Institute recognize children with autism earlier than ever before, paving the way for earlier intervention and improved outcomes
(Baltimore, MD) — In a study published today in the Archives of General Psychiatry, researchers from the Kennedy Krieger Institute in Baltimore, Maryland found that autism can be diagnosed at close to one year of age, which is the earliest the disorder has ever been diagnosed. The study, which evaluated social and communication development in autism spectrum disorders (ASD) from 14 to 36 months of age, revealed that approximately half of all children with autism can be diagnosed around the first birthday. The remaining half will be diagnosed later, and their development may unfold very differently than children whose ASD is diagnosable around the first birthday. Early diagnosis of the disorder allows for early intervention, which can make a major difference in helping children with autism reach their full potential.
Researchers examined social and communication development in infants at high and low risk for ASD starting at 14 months of age and ending at 30 or 36 months (a small minority of the children exited the study at 30 months). Half of the children with a final diagnosis of ASD made at 30 or 36 months of age had been diagnosed with the disorder at 14 months, and the other half were diagnosed after 14 months. Through repeated observation and the use of standardized tests of development, researchers identified, for the first time, disruptions in social, communication and play development that were indicative of ASD in 14-month olds. Multiple signs indicating these developmental disruptions appear simultaneously in children with the disorder.
Dr. Rebecca Landa, lead study author and director of Kennedy Krieger’s Center for Autism and Related Disorders, and her colleagues identified the following signs of developmental disruptions for which parents and pediatricians should be watching:
Abnormalities in initiating communication with others: Rather than requesting help to open a jar of bubbles through gestures and vocalizations paired with eye contact, a child with ASD may struggle to open it themselves or fuss, often without looking at the nearby person.
Compromised ability to initiate and respond to opportunities to share experiences with others: Children with ASD infrequently monitor other people’s focus of attention. Therefore, a child with ASD will miss cues that are important for shared engagement with others, and miss opportunities for learning as well as for initiating communication about a shared topic of interest. For example, if a parent looks at a stuffed animal across the room, the child with ASD often does not follow the gaze and also look at the stuffed animal. Nor does this child often initiate communication with others. In contrast, children with typical development would observe the parent’s shift in gaze, look at the same object, and share in an exchange with the parent about the object of mutual focus. During engagement, children have many prolonged opportunities to learn new words and new ways to play with toys while having an emotionally satisfying experience with their parent.
Irregularities when playing with toys: Instead of using a toy as it is meant to be used, such as picking up a toy fork and pretending to eat with it, children with ASD may repeatedly pick the fork up and drop it down, tap it on the table, or perform another unusual act with the toy.
Significantly reduced variety of sounds, words and gestures used to communicate: Compared to typically developing children, children with ASD have a much smaller inventory of sounds, words and gestures that they use to communicate with others.
“For a toddler with autism, only a limited set of circumstances – like when they see a favorite toy, or when they are tossed in the air – will lead to fleeting social engagement,” said Landa. “The fact that we can identify this at such a young age is extremely exciting, because it gives us an opportunity to diagnose children with ASD very early on when intervention may have a great impact on development.”
The current study reveals that autism often involves a progression, with the disorder claiming or presenting itself between 14 and 24 months of age. Some children with only mild delays at 14 months of age could go on to be diagnosed with ASD. Landa and her colleagues observed distinct differences in the developmental paths, or trajectories, of children with early versus later diagnosis of ASD. While some children developed very slowly and displayed social and communication abnormalities associated with ASD at 14 months of age, others showed only mild delays with a gradual onset of autism symptoms, culminating in the diagnosis of ASD by 36 months.
If parents suspect something is wrong with their child’s development, or that their child is losing skills during their first few years of life, they should talk to their pediatrician or another developmental expert. This and other autism studies suggest that the “wait and see” method, which is often recommended to concerned parents, could lead to missed opportunities for early intervention during this time period.
“What’s most exciting about these important advancements in autism diagnosis is that ongoing intervention research leads us to believe it is most effective and least costly when provided to younger children,” said Dr. Gary Goldstein, President and CEO of the Kennedy Krieger Institute. “When a child goes undiagnosed until five or six years old, there is a tremendous loss of potential for intervention that can make a marked difference in that child’s outcome.”
While there are currently no standardized, published criteria for diagnosing children with autism at or around one year of age, Landa’s goal is to develop these criteria based on this and other autism studies currently underway at the Kennedy Krieger Institute. Landa and her colleagues at the Institute plan on releasing preliminary diagnostic criteria for very young children with autism in an upcoming report.
Participants in the current study included infants at high risk for ASD (siblings of children with autism, n=107) and low risk for ASD (no family history of autism, n=18). Standardized tests of development and play-based assessment tools were used to evaluate social interaction, communication and play behaviors in both groups at 14, 18 and 24 months of age. Researchers assigned diagnostic impressions at every age, indicating whether there were clinically significant signs of delay or impairment. After their last evaluation at 30 or 36 months, each participant was then given a final diagnostic classification of ASD, non-ASD impairment, or no impairment. The ASD group was further divided into an Early ASD diagnosis group and a Later ASD diagnosis group based on whether they were given a diagnosis of ASD at 14 or 24 months.
Autism spectrum disorders (ASD) is the nation’s fastest growing developmental disorder, with current incidence rates estimated at 1 in 150 children. This year more children will be diagnosed with autism than AIDS, diabetes and cancer combined, yet profound gaps remain in our understanding of both the causes and cures of the disorder. Continued research and education about developmental disruptions in individuals with ASD is crucial, as early detection and intervention can lead to improved outcomes in individuals with ASD.
About the Kennedy Krieger Institute
Internationally recognized for improving the lives of children and adolescents with disorders and injuries of the brain and spinal cord, the Kennedy Krieger Institute in Baltimore, MD serves more than 13,000 individuals each year through inpatient and outpatient clinics, home and community services and school-based programs. Kennedy Krieger provides a wide range of services for children with developmental concerns mild to severe, and is home to a team of investigators who are contributing to the understanding of how disorders develop while pioneering new interventions and earlier diagnosis. For more information on Kennedy Krieger Institute, visit http://www.kennedykrieger.org.
- 25-hydroxyvitamin D
- Acetaminophen and Caffeine
- Acinetobacter calcoaceticus-baumannii complex
- acute lymphoblastic leukemia
- American Academy of Neurology
- American Association for Cancer Research
- American Chemical Society
- American College of Cardiology
- American Heart Association
- American Journal of Clinical Nutrition
- American Journal of Public Health
- American Legacy Foundation
- Ancestral Heritage
- Archives of Neurology
- Arthritis & Rheumatism
- Autism Spectrum Disorders
- Autoimmune Diseases
- B. Rappaport Faculty of Medicine at Technion in Haifa
- Biological Sciences
- Blackwell Publishing Ltd.
- Bone Demineralisation
- Bone Diseases
- British Medical Journal
- Brooke Army Medical Center
- Buck Institute
- Calabria Regional Health Department
- Canadian Institutes of Health Research
- Cancer Biology
- Cancer Biology and Therapy
- Cancer Information In Spanish
- Cardiovascular Disease
- Catalan Institute of Oncology in Spain
- Childhood Lukemia
- Childhood Nutrition
- Children's Hospital of Philadelphia
- Children’s Cancer Institute Australia
- Children’s Hospital
- Children’s Hospital of Philadelphia
- Childrens Hospital Los Angeles
- Chromosome 17
- Chromosome 8
- Chronic Multisymptom Illnesses
- Chronic Stress
- Chronic Stress and Obesity
- CHS National Cancer Control Center and Technion
- CHS National Israeli Cancer Control Center
- Clinical Applications
- Clinical Trials
- College of Medicine in Houston
- Complex Chronic Conditions
- Cornell University
- Cytochrome b5
- Cytochrome P450
- Drug Abuse
- Duke University Medical Center
- Electronic Health Records
- Emergency Preparedness
- Emergency Room
- Emory Genetics Laboratory
- Emory University
- End Of Life Care
- European Cancer Conference
- European Journal of Cancer Care
- European League Against Rheumatism
- European Science Foundation
- FDA Warnings
- Fibromyalgia News
- FMS Global News
- Folic Acid
- Fort Sam Houston
- Fox Chase Cancer Center
- Fred Hutchinson Cancer Research Center
- Garvan Institute of Medical Research
- General Psychiatry
- Genetic Link
- Genetic Marker C allele of rs10505477
- Global Health Vision
- Global News
- Health Canada
- Health Information Technology
- Heart Disease
- Hebrew University of Jerusalem
- Hemorrhagic Stroke
- Historical Medicine
- Hospital Epidemiology
- Hospital Trauma
- Howard Hughes Medical Institute
- Human Genome
- Huntington's disease
- Imperial College London
- Interactive Autism Network
- Inuit children
- Irving Weinstein Foundation
- JAMA/Archives journals
- Japanese Society for the Promotion of Science
- Johns Hopkins University
- Joint Health Research Program
- journal BBA Biomembranes
- journal Cell
- journal Nature Genetics
- Journal of Clinical Investigation
- Journal of Experimental Social Psychology
- Journal of the American College of Surgeons
- Journal of Theoretical Biology
- Juvenile Diabetes
- Karolinska Institute in Stockholm
- Kennedy Krieger Institute
- Kyowakai Hospital
- Lamezia Terme
- London UK Feed
- Lung Cancer
- Massachusetts General Hospital
- Mayo Clinic
- McMaster University
- Medical History
- Medical Insurance
- Medical Journals
- Mitochondrial Diseases
- Molecular Biology
- Molecular Epidemiology
- Multiple Sclerosis
- Muscular Dystrophy
- Music Video Of The Day
- Music Video Pick Of The Day
- National Cancer Institute
- National Institute on Aging
- National Institutes of Health
- Nature Genetics
- Neurodegenerative Diseases
- Neuropeptide Y
- New England Journal of Medicine
- New York University
- News Australia
- News Canada
- News France
- News Germany
- News Israel
- News Italy
- News Jerusalem
- News Switzerland
- News UK
- News US
- News USA
- non-Hodgkin's lymphoma
- Northwestern University
- Nova Scotia
- Nutritional Anthropology
- Oak Ridge National Laboratory
- Occupational Health
- omega-3 fatty acids
- Orthopaedic Research Society
- Ottawa City Feed
- Oxford University
- Pain Management
- Palliative Care
- Parkinson Society of Canada
- Pediatric Palliative Care
- Peutz-Jeghers syndrome
- Pharmacology and Neuroscience
- Pick's Disease
- Pre/Post Natal Care
- Preventive Medicine
- Prince Edward Island
- Protein Growth Factor
- Public Health
- Research Australia
- Rheumatoid Arthritis
- RSS Feed
- Rush Alzheimer’s Disease Center
- Seattle Washington
- Spina Bifida
- Spinal Cord Injuries
- St. Elmos Fire
- St. Jude Children's Research Hospital
- Statin Drugs
- Stem Cells
- Sydney Children’s Hospital
- Systemic Lupus Erythematosus
- Temple University
- The American Academy of Neurology
- the Israel Institute of Technology
- Toronto City Feed
- trauma-associated and hospital-acquired infection
- Type 1 Diabetes
- Type 2 Diabetes
- Université Laval
- University College London
- University Hospital in Geneva
- University New South Wales
- University of Bern
- University of Calgary
- University of California
- University of Chicago
- University of Chicago Press Journals
- University of Florida
- University of Granada
- University of Manchester
- University of Michigan
- University of Missouri
- University of North Carolina
- University of North Texas
- University of Nottingham
- University of Oregon
- University of Pennsylvania School of Medicine
- University of Pittsburgh
- University of Rochester
- University of Toronto
- US Army soldiers in Iraq
- US Military Hospitals
- UT Southwestern Medical Center
- Vitamin D
- W. Garfield Weston Fellows
- Wake Forest University Baptist Medical Center
- Washington DC
- Washington DC City Feed
- Washington University
- Weather Anomolies
- Weill Medical College
- Wellcome Trust
- World Health Organisation
- World News
- Yale University