HIGHLIGHTS

GENOME WATCH Shrinking genomics Nicholas R. Thomson, Mohammed Sebaihia, Ana M. Cerdeño-Tárraga, Matthew T. G. Holden and Julian Parkhill.

Two bacteria are featured this month, and both evolution in their new and isolated niches. DNA encoding proteins (522 CDSs) and stable are at the lower end of the genome size scale. M. gallisepticum is a heavyweight in this group RNA. N. equitans lacks the genes for de novo The first, gallisepticum, belongs to with a genome of 0.99 Mb that encodes a pre- biosynthesis of amino acids, , cofac- a group of bacteria that have been studied both dicted 742 coding sequences (CDSs). Compara- tors, and — consistent with its parasitic as important human and animal pathogens and tive analysis of the indicates that lifestyle. One striking feature of the N. equitans in the pursuit of understanding the essential the minimal gene-set is 265–350 essential genes. genome is the presence of multiple ‘split genes’, functions of a self-replicating minimal cell. The Responsible for avian chronic respiratory the products of which are encoded by single second, , is an infections, this economically important genes in most other microorganisms, but obligate symbiont that only grows in co-culture pathogen is spread by aerosols and vertical which, in this organism, are encoded by two dis- with another archaeon. N. equitans seems to transmission. Over 10% of the CDSs in the crete CDSs, both of which are required for full be the coelacanth of the microbial world — it genome encode products that belong to a par- functionality. The split sites for many of these has been assigned to a new and alogous multi-gene family distributed between genes are between domains that are present in represents a primitive form of prokaroytic life. five loci that encodes 43 variable lipoproteins. the assembled protein product. The authors Variations in the sequences of the lipoprotein speculate that multi-domain proteins might Mycoplasma gallisepticum is the sixth and latest genes are thought to produce enough antigenic have evolved from the fusion of two or more mycoplasma species to be fully sequenced1, variation to facilitate immune evasion. Only single domain proteins. The split genes in N. the previous being one member of this family is usually expressed equitans could be a view of the ancestral state of (0.58-Mb genome; human host), Mycoplasma at any one time and there is evidence of phase genes from early in microbial evolution. This, pneumoniae (0.82-Mb genome; human host), variation. The proteins encoded by many of together with other facets of the N. equitans Ureaplasma urealyticum (0.75-Mb genome; these lipoprotein genes are predicted to have lifestyle, such as its anaerobic and high-temper- human host), Mycoplasma pulmonis (0.96-Mb lectin-binding domains, which might have a ature growth, indicate a primitive existence. The genome; rodent hosts) and Mycoplasma pene- role in adherence to host cells. authors concluded that N. equitans has not trans (1.35-Mb genome; human host). Myco- There are many other membrane-associated undergone a process of reductive evolution — plasmas are parasitic intracellular pathogens proteins in M. gallisepticum, including several like the mycoplasmas — but could represent a that are thought to have descended from a predicted transport proteins and a pared down living microbial fossil. Gram-positive ancestor with a low G+C con- — but still thought to be functional — set of the As we begin a new year, the pace of microbial tent, and undergone a process of reductive Sec translocation proteins. Twelve transposases genome sequencing shows no sign of abating. that were identified seem to be responsible for Even though the range of genomes sequenced continued gene rearrangements and loss. Of the has broadened in scope to include more exotic 742 predicted CDSs, 36% are in the ‘unique’ or and unusual prokaryotes, such as N. equitans ‘conserved hypothetical’ protein category, high- and the planctomycete Pirellula, the Gamma lighting our lack of understanding of even these purple and the Gram-positive simple microorganisms. bacteria are still dominant (FIG. 1). In a similar Lilliputian vein, the genome of Nicholas R. Thomson, Mohammed Sebaihia, Nanoarchaeum equitans, at 0.49 Mb, is even Ana M. Cerdeño-Tárraga, Matthew T.G. Holden and smaller than that of M. genitalium; it is not only Julian Parkhill are at the Sanger Institute, the smallest archaeal genome sequenced, but Wellcome Trust Genome Campus, Hinxton, the smallest microbial genome sequenced so Cambridge CB10 1SA, UK. 2 e-mail: [email protected] far . N. equitans is a newly discovered hyper- doi:10.1038/nrmicro800 thermophilic archaeon, which only grows in co-culture with another archaeon, sp. 1. Papazisi, L. et al. The complete genome sequence of the avian pathogen Mycoplasma gallisepticum strain Rlow. Ribosomal protein and rRNA-based phylo- Microbiology 149, 2307–2316 (2003). genies have placed the branching point of 2. Waters, E. et al. The genome of Nanoarchaeum equitans: insights into early archaeal evolution and derived parasitism. Planctomycetes Chlamydias N. equitans evolution early in the archaeal Proc. Natl Acad. Sci. 100, 12984–12988 (2003). Cytophaga-Flavobacterium- Cyanobacteria lineage, before that of the , Bacteroides group 2 and Korarchaeota, so it has Online links ε-purple group γ-purple group been placed in a fourth phylum of the DATABASES α β-purple group -purple group — the . The following terms in this article are linked online to: Gram-positive group Spirochaetes Entrez: http://www.ncbi.nlm.nih.gov/Entrez/ Unlike other prokaryotes with a similar Mycoplasma gallisepticum | Nanoarchaeum equitans Figure 1 | Prokaryotic genomes published in genome size, there is little evidence for reductive FURTHER INFORMATION 2003. Data taken from the Genomes OnLine evolution in this genome. The N. equitans Genomes OnLine Database: http://www.genomesonline.org/ Database (see Online links). genome has a high gene density, with 95% of its Access to this interactive links box is free online.

NATURE REVIEWS | MICROBIOLOGY VOLUME 2 | JANUARY 2004 | 11