Impact of Bacterial-Animal Lateral Gene Transfer on Human Health

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DESCRIPTION (Provided by the applicant) Abstract: Lateral gene transfer (LGT), the transfer of DNA between diverse organisms, allows organisms to acquire new genes and phenotypes. Most described LGT events occur within a single domain of life with most cases described in eubacteria. More infrequently, interdomain LGT occurs where DNA moves between two domains of life (e.g. between eubacteria and eukaryotes). Interdomain LGT may have two medically important implications. About 120 million people are afflicted with the filariasis and an estimated 18% of the world¿s population is at risk for developing the disease. Filarial nematodes (the causative agents) are known to acquire DNA from their bacterial endosymbionts, Wolbachia. Although in some nematodes Wolbachia are obligate endosymbionts, other lineages lack Wolbachia. Can lateral gene transfer facilitate endosymbiont loss? If so, can current antibiotic therapies drive endosymbiont loss? Can laterally transferred genes serve as alternative, novel drug targets? Our experiments aim to better characterize the extent and diversity of such transfers in filarial nematodes and to assess their functional significance. The second case involves LGT from bacteria to humans. Approximately 90% of the cells in the human body are commensal and pathogenic bacteria. Thus, our mucosal cells are bathed in bacterial DNA. Does this bacterial DNA get incorporated into the chromosomes of our somatic cells? Could such integrations lead to gene disruptions in somatic cells analogous to disease causing mutations resulting from insertion of retroviruses, transposons, or mitochondrial DNA? The American Cancer Society estimates that 10% of cancers in developed countries are linked to infections, although many of the mechanisms are unknown. Could proto- oncogene disruption by bacterial DNA lead to development of bacteria-associated cancers? Through a thorough analysis of available sequencing data, we have already identified potential cases of bacteria-human lateral gene transfer. We propose a more comprehensive survey as well as experiments aimed at validating such transfers. Public Health Relevance: The transfer of bacterial DNA to vertebrate animal genomes (including humans) may have important implications in (a) the control and treatment of human lymphatic filariasis and (b) mutating human genes leading to important diseases like cancer. The experiments proposed aim at a more comprehensive search for such events, validation of identified transfers, and functional characterization.