Genetic Variation in Human Gut Viruses Could Be Raw Material for Inner Evolution, Penn Study Finds

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Media Contact:Karen Kreeger | Karen.kreeger@uphs.upenn.edu | 215-349-5658March 15, 2012

A growing body of evidence underscores the importance of human gut bacteria in modulating human health, metabolism, and disease. 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.

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