Anonymous probes from the genome of Halobacterium salinarium GRB and 12 gene probes were hybridized to the cosmid clones representing the chromosome and plasmids of Halobacterium salinarium GRB and Haloferax volcanii DS2. The order of and pairwise distances between 35 loci uniquely cross-hybridizing to both chromosomes were analyzed in a search for conservation. No conservation between the genomes could be detected at the 15-kbp resolution used in this study. We found distinct sets of low-copy-number repeated sequences in the chromosome and plasmids of Halobacterium salinarium GRB, indicating some degree of partitioning between these replicons. We propose alternative courses for the evolution of the haloarchaeal genome: (i) that the majority of genomic differences that exist between genera came about at the inception of this group or (ii) that the differences have accumulated over the lifetime of the lineage. The strengths and limitations of investigating these models through comparative genomic studies are discussed.In recent years much effort has been devoted to genomelevel analysis among prokaryotes (11,15). Most of this effort involved the use of pulsed-field gel electrophoresis (PFGE), either in the construction of physical maps or in the direct comparison of restriction fragment patterns. The latter method allows for a large number of genomes to be quickly and relatively easily compared but suffers from poor resolution, although it has been useful in the typing of strains (18,22,32). A large number of studies have been conducted by using PFGE to construct physical maps (for a review, see reference 11). Most often, genetic markers are then localized to specific regions of the map through hybridization, allowing the investigation of gross rearrangements at the genomic level. Genetic loci occurring on the same restriction fragment, however, cannot be ordered on the map, masking any differences in their arrangement. This limitation restricts such comparisons to closely related genomes.The majority of genomic comparisons performed to date have used PFGE-derived maps to compare genomes at the strain or species level. The results of these comparisons have prompted their division into two groups (15), organisms with highly conserved genetic maps and those with divergent maps. (16), and Leptospira interrogans (48). The criteria for deciding in which group a comparison will be included have not been rigorously established, however. Typically, no objective measure is used to determine the degree of similarity between genomes, which makes relating the results of one comparison to those of another problematic. Indeed, genomes showing a moderate number of differences could be considered either conserved or divergent, depending on the context of the study.Of the more than 100 chromosomal maps available, only 10 are from members of the domain Archaea. To date, three archaeal genomic comparisons have been performed, one between two methanogens (46) and two between different members of the haloarchaea (19, 31). The most de...
