The Nanoarchaeota: Physiology, Genomics and Phylogeny 1 2 Ana Casanueva, Marla Tuffin and Don A Cowan * 3 4 Institute for Microbial Biotechnology and Metagenomics, Department of Biotechnology, University of the 5 Western Cape, Bellville, 7535, South Africa 6 7 * Correspondence to: Don A Cowan; Institute for Microbial Biotechnology and 8 Metagenomics, Department of Biotechnology, University of the Western Cape, Private 9 Bag X17, Bellville, 7535, South Africa; Phone: (+2721) 959 2083; Fax: (+2721) 959 10 3505; Email: dcowan@uwc.ac.za 11 12 13 14 Abstract 15 The Nanoarchaeota, proposed as the fourth sub-division of the Archaea in 2002, are 16 known from a single isolate, “Nanoarchaeum equitans”, which exists in a symbiotic 17 association with the hyperthermophilic Crenarchaeote, Ignicoccus hospitalis. The 18 sequencing of both genomes has provided clues on their unusual and very specific 19 association. The discovery of nanoarchaeal sequences in diverse geographical 20 hyperthermophilic locations, and most importantly the identification of nanoarchaeal 21 phylotypes in mesophilic halophilic environments suggest the possibility of either free- 22 living nanoarchaeotes or associations with novel hosts. The “true” phylogenetic position 23 of the Nanoarchaea is still a matter of debate, having been described originally as a 24