In vitro studies of the haloarchaeal genus have demonstrated their ability to frequently exchange DNA between species, whereas rates of homologous recombination estimated from natural populations in the genus decreased the affinity for penicillin, increasing resistance to the antibiotic. genetic transfer (HGT), combined with high rates of gene loss, can lead to substantial differences in gene content between Forskolin pontent inhibitor members of the same species (Makarova et al. 1999; Welch et al. 2002; Thompson et al. 2005; Normand et al. 2007). These and other reports in the literature imply the generation of genetic and phenotypic diversity during microbial evolution has been from mutations in apparently clonal or recombining populations, and HGT between populations and species. HGT generates mosaic-like microbial genomes (Lawrence and Ochman 1998; Welch et al. 2002), a result that questions the validity of describing prokaryote diversity and evolutionary history with a tree-like model or using terms such as lineages or species (Hilario and Gogarten 1993; Doolittle 1999; Martin 1999; Doolittle and Zhaxybayeva 2009; Koonin et Forskolin pontent inhibitor al. 2011; Williams et al. 2011). Genome-scale comparative analyses provide unprecedented insight into the evolutionary histories of organisms allowing us to characterize and quantify the processes involved. One set of organisms for which several whole-genome sequences are available is the haloarchaea (class: Halobacteria; division Euryarchaeota [Grant et al. 2001]). Haloarchaea are Hhex typically found in salterns, hypersaline marshes and lakes, and inland seas such as the Dead Sea and the Great Salt Lake where they often dominate the microbial community (Antn et al. 1999; Oren 2008). Most members are extreme halophiles requiring 10% (w/v) NaCl for growth and K+ as a compatible solute, with the associated adaptation of an acidic proteome (Danson and Hough 1997). However, some estuarine isolates grow at 2.5% (w/v) NaCl (Purdy et al. 2004). As a group, the haloarchaea are metabolically diverse heterotrophs (Falb et al. 2008) that respire using oxygen and sometimes nitrate (Oren 2008), although demonstrates a narrow range of compounds required for growth: for example, glycerol (Bolhuis et al. 2004), pyruvate (Burns et al. 2007), or dihydroxyacetone (Bardavid and Oren 2008). Unusual for archaea, many representatives of the haloarchaea harbor multiple large ( 100 kbp) replicons classed as chromosomes if they host essential genes or as megaplasmids if they do not (DasSarma et al. 2009). Haloarchaea have an unusual mating system involving intercellular cytoplasmic bridges between cells (Rosenshine et al. 1989) and can be artificially transformed in the laboratory (Cline and Doolittle 1992). A recent report by Naor et al. (2012) demonstrated the frequent formation of viable hybrids following recombination between two species, and there is also evidence that haloarchaea are highly recombinogenic in nature. Multilocus sequence analysis (MLSA) of strains classified as belonging to the genus isolate (DSM 16790) with an environmental metagenome, both sampled from the same solar saltern in Spain, showed multiple chromosomal regions to be underrepresented in the environment, whereas contiguous regions of environmental fragments only partially matched regions of the sequenced genome. It was concluded that the wider community contains a large gene repertoire and is highly recombinogenic (Legault et al. 2006; Cuadros-Orellana et al. 2007). A comparison of the genome with that of another strain (DSM Forskolin pontent inhibitor 16854) isolated from Australia revealed a putative, mechanistically coupled insertion and deletion system, causing different sequences to be integrated at exactly the same position on the chromosome (Dyall-Smith et al. 2011). Although monophyly of Haloarchaea was observed for the 16S ribosomal RNA (rRNA) gene (Arahal et al. 2002), this genetic marker is not without criticism for establishing within group relationships because strains from several genera ([Mylvaganam and Dennis 1992],.