Yet bacteria are only part of the story. Viruses that infect those bacteria also shape who we are. Frederic D. Bushman, PhD, professor of Microbiology at the Perelman School of Medicine at the University of Pennsylvania, led a study published this month in the Proceedings of the National Academy of Sciences that sequenced the DNA of viruses -- the virome -- present in the gut of healthy people.
Nearly 48 billion bases of DNA, the genetic building blocks, were collected in the stools of 12 individuals. The researchers then assembled the blocks like puzzle pieces to recreate whole virus genomes. Hundreds to thousands of likely distinct viruses were assembled per individual, of which all but one type were bacteriophages — viruses that infect bacteria -- which the team expected. The other was a human pathogen, a human papillomavirus found in a single individual. Bacteriophages are responsible for the toxic effects of many bacteria, but their role in the human microbiome has only recently started to be studied.
To assess variability in the viral populations among the 12 individuals studied, Bushman's team, led by graduate student Samuel Minot, looked for stretches of bases that varied the most.
Their survey identified 51 hypervariable regions among the 12 people studied, which, to the team's surprise, were associated with reverse transcriptase genes. Reverse transcriptase enzymes, more commonly associated with replication of retroviruses such as HIV, copy RNA into DNA. Of the 51 regions, 29 bore sequence and structural similarity to one well-studied reverse transcriptase, a hypervariable region in the Bordetella bacteriophage BPP-1. Bordetella is the microbe that causes kennel cough in dogs.
BPP-1 uses reverse transcriptase and an error-prone copying mechanism to modify a protein to aid in entering and reproducing in a wide array of viral targets. Bushman and colleagues speculate that the newly discovered hypervariable regions could serve a similar function in the human virome, and microbiome, by extension.
"It appears there's natural selective pressure for rapid variation for these classes of bacteriophages, which implies there's a corresponding rapidly changing environmental factor that the phage must be able to quickly adapt to," says Minot. Possible reasons for change, say the authors, include evading the immune system and keeping abreast of ever-evolving bacterial hosts — a kind of mutation-based host-pathogen arms race. Whatever the case, Minot says, such variability may be helping to drive evolution of the gut microbiome: "The substrate of evolution is mutation."
Evolutionary analysis of the 185 reverse transcriptases discovered in this study population suggests that a large fraction of these enzymes are primarily involved in generating diversity. Now, Minot says, the challenge is to determine the function of the newly discovered hypervariable regions, and understand how their variability changes over time and in relationship to disease.
"This method opens a whole new world of 'diversity-generating' biology to discover what these clearly important systems are actually doing," he says.
In addition to Bushman and Minot, co-authors are Stephanie Grunberg (Department of Microbiology); Gary Wu (Division of Gastroenterology); and James Lewis (Department of Biostatistics and Epidemiology), all from Penn.
The research was supported by grants from the National Institutes of Health, Pennsylvania Department of Health, and the Crohn's and Colitis Foundation of America.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $479.3 million awarded in the 2011 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital — the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2011, Penn Medicine provided $854 million to benefit our community.
Karen Kreeger | EurekAlert!
Antibiotic resistances spread faster than so far thought
18.02.2019 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
The Lypla1 Gene Impacts Obesity in a Sex-Specific Manner
18.02.2019 | Deutsches Zentrum für Diabetesforschung
For the first time, an international team of scientists based in Regensburg, Germany, has recorded the orbitals of single molecules in different charge states in a novel type of microscopy. The research findings are published under the title “Mapping orbital changes upon electron transfer with tunneling microscopy on insulators” in the prestigious journal “Nature”.
The building blocks of matter surrounding us are atoms and molecules. The properties of that matter, however, are often not set by these building blocks...
Scientists at the University of Konstanz identify fierce competition between the human immune system and bacterial pathogens
Cell biologists from the University of Konstanz shed light on a recent evolutionary process in the human immune system and publish their findings in the...
Laser physicists have taken snapshots of carbon molecules C₆₀ showing how they transform in intense infrared light
When carbon molecules C₆₀ are exposed to an intense infrared light, they change their ball-like structure to a more elongated version. This has now been...
The so-called Abelian sandpile model has been studied by scientists for more than 30 years to better understand a physical phenomenon called self-organized...
Physicists from the University of Basel have developed a new method to examine the elasticity and binding properties of DNA molecules on a surface at extremely low temperatures. With a combination of cryo-force spectroscopy and computer simulations, they were able to show that DNA molecules behave like a chain of small coil springs. The researchers reported their findings in Nature Communications.
DNA is not only a popular research topic because it contains the blueprint for life – it can also be used to produce tiny components for technical applications.
11.02.2019 | Event News
30.01.2019 | Event News
16.01.2019 | Event News
18.02.2019 | Interdisciplinary Research
18.02.2019 | Process Engineering
18.02.2019 | Studies and Analyses