Populations of human cells have a constant, intimate relationship with the human microbiome. With that comes a potential for lateral gene transfer that could be analogous to disease-causing DNA insertions by transposons, retroviruses, or mitochondria. Putative integrations of bacterial DNA in human tissues, including tumors, can be detected with next-generation sequencing. Hosts Vincent Racaniello, Elio Schaechter, Jo Handelsman and Michelle Swanson review evidence for bacterial DNA integrated into the human genome, and control of the symbiont population in an insect midgut.

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TWiM #69: Bacterial DNA in the human genome

Journal reference: Riley DR, Sieber KB, Robinson KM, White JR, Ganesan A, Nourbakhsh S, Hotopp JCD. Bacteria-Human Somatic Cell Lateral Gene Transfer Is Enriched in Cancer Samples. PLoS Comput Biol 9(6): e1003107. doi:10.1371/journal.pcbi.1003107.

Journal abstract: There are 10× more bacterial cells in our bodies from the microbiome than human cells. Viral DNA is known to integrate in the human genome, but the integration of bacterial DNA has not been described. Using publicly available sequence data from the human genome project, the 1000 Genomes Project, and The Cancer Genome Atlas (TCGA), we examined bacterial DNA integration into the human somatic genome. Here we present evidence that bacterial DNA integrates into the human somatic genome through an RNA intermediate, and that such integrations are detected more frequently in (a) tumors than normal samples, (b) RNA than DNA samples, and (c) the mitochondrial genome than the nuclear genome. Hundreds of thousands of paired reads support random integration of Acinetobacter-like DNA in the human mitochondrial genome in acute myeloid leukemia samples. Numerous read pairs across multiple stomach adenocarcinoma samples support specific integration of Pseudomonas-like DNA in the 5′-UTR and 3′-UTR of four proto-oncogenes that are up-regulated in their transcription, consistent with conversion to an oncogene. These data support our hypothesis that bacterial integrations occur in the human somatic genome and may play a role in carcinogenesis. We anticipate that the application of our approach to additional cancer genome projects will lead to the more frequent detection of bacterial DNA integrations in tumors that are in close proximity to the human microbiome.

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