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Mor Lurie-Weinberger Inter-domain lateral gene transfer - the case of methanogenic archaea Abstract: Atmospheric methane (CH4) is a potent green house gas, with global warming potential 21 times that of CO2. Methane emissions from agriculture represent around 40% of the emissions produced by human activities, thetechnologies to reduce these emissions are lacking. Additionally, cattle typically lose 6 % of ingested energy as methane, so inhibiting methanogenic metabolism in cattle is highly desirable in agriculture. Ruminant methane is formed by the action of methanogenic archaea typified by Methanobrevibacter ruminantium, and Methanobrevibacter smithii, two wide-spread mammal-associated microorganisms. M. smithii is also the most abundant methanogen in the human, with a genome which is “tailored” to the intestinal environment. Since the mammalian intestine is a niche predominantly colonized by a multitude of bacterial species, it's likely that the genomes of methanogenic Archaea in the intestines have acquired their ability to prosper in this environment through inter-domain lateral gene transfer (LGT) from bacterial species that dominate this niche. An automatic phylogenetic pipeline was utilized to identify LGT genes in M. smithii. 298 LGT candidates were found, representing 18% of the genome. The majority of these genes (88%) appear to be the result of LGT from Bacteria into Archaea. These genes represent promising targets for intervention, as their loss is expected to have an adverse effect on these microorganisms' survival in ruminants. While many archaeal genes are similar to those of eukaryotes, and therefore problematic targets for manipulation, genes derived from LGT from bacteria are absent from eukaryotes, and are thereby safer targets for manipulation, and might be used to reduce humaninduced global warming.