Nature 396, 133 - 140 (1998)
The genome sequence of Rickettsia prowazekii and the origin of mitochondria
SIV G. E. ANDERSSON*, ALIREZA ZOMORODIPOUR*, JAN O. ANDERSSON*, THOMAS SICHERITZ-PONTÉN*, U. CECILIA M. ALSMARK*, RAF M. PODOWSKI*, A. KRISTINA NÄSLUND*, ANN-SOFIE ERIKSSON*, HERBERT H. WINKLER & CHARLES G. KURLAND*
* Department of Molecular Biology, University of Uppsala, Uppsala S-75124, Sweden
Department of Microbiology and Immunology, University of South Alabama, Mobile, Alabama 36688, USA
Correspondence and requests for materials should be addressed to C.G.K.
(e-mail:
chuck@xray.bmc.uu.se).
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 profiles 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 Such genes seem to have been replaced by homologues in the nuclear (host) genome.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 alpha-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 2030 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 organisms2-4, 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 alpha-proteobacteria5,6. Indeed, the closest extant relatives of the ancestor to mitochondria seem to be the Rickettsia 7-10. That modern Rickettsia favour an intracellular lifestyle identifies these bacteria as the sort of organism that might have initiated the endosymbiotic scenario leading to modern mitochondria11. 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 genomes2-4. Thus Rickettsia, like mitochondria, are good examples of highly derived genomes, the products of several types of reductive evolution.