We describe here the complete genome sequence (1,111,523 base pairs) of the obligate intracellular parasite Rickettsia prowazekii, the causative agent of epidemic typhus. This genome contains 834 protein-coding genes. The functional pro®les of these genes show similarities to those of mitochondrial genes: no genes required for anaerobic glycolysis are found in either R. prowazekii or mitochondrial genomes, but a complete set of genes encoding components of the tricarboxylic acid cycle and the respiratory-chain complex is found in R. prowazekii. In effect, ATP production in Rickettsia is the same as that in mitochondria. Many genes involved in the biosynthesis and regulation of biosynthesis of amino acids and nucleosides in free-living bacteria are absent from R. prowazekii and mitochondria. Such genes seem to have been replaced by homologues in the nuclear (host) genome. The R. prowazekii genome contains the highest proportion of non-coding DNA (24%) detected so far in a microbial genome. Such non-coding sequences may be degraded remnants of`neutralized' genes that await elimination from the genome. Phylogenetic analyses indicate that R. prowazekii is more closely related to mitochondria than is any other microbe studied so far.The Rickettsia are a-proteobacteria that multiply in eukaryotic cells only. R. prowazekii is the agent of epidemic, louse-borne typhus in humans. Three features of this endocellular parasite deserve our attention. First, R. prowazekii is estimated to have infected 20±30 million humans in the wake of the First World War and killed another few million following the Second World War (ref. 1). Because it is the descendent of free-living organisms 2±4 , its genome provides insight into adaptations to the obligate intracellular lifestyle, with probable practical value. Second, phylogenetic analyses based on sequences of ribosomal RNA and heat-shock proteins indicate that mitochondria may be derived from the aproteobacteria 5,6 . Indeed, the closest extant relatives of the ancestor to mitochondria seem to be the Rickettsia 7±10 . That modern Rickettsia favour an intracellular lifestyle identi®es these bacteria as the sort of organism that might have initiated the endosymbiotic scenario leading to modern mitochondria 11 . Finally, the genome of R. prowazekii is a small one, containing only 1,111,523 base pairs (bp). Its phylogenetic placement and many other characteristics identify it as a descendant of bacteria with substantially larger genomes 2±4 . Thus Rickettsia, like mitochondria, are good examples of highly derived genomes, the products of several types of reductive evolution.The genome sequence of R. prowazekii indicates that these three features may be related. For example, prokaryotic genomes evolving within a cell dominated by a much larger, eukaryote genome and constrained by bottle-necked population dynamics will tend to lose genetic information 12,13 . Predictable sets of expendable genes will tend to disappear from the prokaryotic genome when they are made redundant by the activit...

Transitions to obligate intracellular parasitism have occurred at numerous times in the evolutionary past. The genome sequences of two obligate intracellular parasites, Rickettsia prowazekii and Chlamydia trachomatis, were published last year. A comparative analysis of these two genomes has revealed examples of reductive convergent evolution, such as a massive loss of genes involved in biosynthetic functions. In addition, both genomes were found to encode transport systems for ATP and ADP, not otherwise found in bacteria. Here, we discuss adaptations to intracellular habitats by comparing the information obtained from the recently published genome sequences of R. prowazekii and C. trachomatis.z 1999 Federation of European Biochemical Societies.

We describe here the organization of the rRNA genes in Rickettsia prowazekii. In this organism, the 23S and the 5S rRNA genes are tightly linked to each other, whereas the 16S rRNA gene is separated from this cluster. The 23S-5S unit is preceded by the methionyl-tRNAfMet formyltransferase gene.

The survival of the HAD-MSCs for a period of 90 days in VH and even longer period of up to 6 months in other eye tissues makes them a promising source to be considered in regenerative medicine of eye diseases. However, the potency of crossing the BRB by the implanted cells suggests that use of HAD-MSCs must be handled with extreme caution.

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