Genome degradation is an ongoing process in Rickettsia.

To study reductive evolutionary processes in bacterial genomes, we examine sequences in the Rickettsia genomes which are unconstrained by selection and evolve as pseudogenes, one of which is the metK gene, which codes for AdoMet synthetase. Here, we sequenced the metK gene and three surrounding genes in eight different species of the genus Rickettsia. The metK gene was found to contain a high incidence of deletions in six lineages, while the three genes in its surroundings were functionally conserved in all eight lineages. A more drastic example of gene degradation was identified in the metK downstream region, which contained an open reading frame in Rickettsia felis. Remnants of this open reading frame could be reconstructed in five additional species by eliminating sites of frameshift mutations and termination codons. A detailed examination of the two reconstructed genes revealed that deletions strongly predominate over insertions and that there is a strong transition bias for point mutations which is coupled to an excess of GC-to-AT substitutions. Since the molecular evolution of these inactive genes should reflect the rates and patterns of neutral mutations, our results strongly suggest that there is a high spontaneous rate of deletions as well as a strong mutation bias toward AT pairs in the Rickettsia genomes. This may explain the low genomic G + C content (29%), the small genome size (1.1 Mb), and the high noncoding content (24%), as well as the presence of several pseudogenes in the Rickettsia prowazekii genome.

[1]  H. Muller THE RELATION OF RECOMBINATION TO MUTATIONAL ADVANCE. , 1964, Mutation research.

[2]  E. S. Murray,et al.  Rickettsiae and rickettsial diseases. , 1973, Bulletin of the World Health Organization.

[3]  D. Millar,et al.  DNA Base Composition of Rickettsiae , 1973, Science.

[4]  Dcoxyribonucleic acid base composition of rickettsiae belonging to the Rocky Mountain spotted fever group isolated in Czechoslovakia. , 1974 .

[5]  J. Felsenstein The evolutionary advantage of recombination. , 1974, Genetics.

[6]  C. Wisseman,et al.  Infection cycle of Rickettsia rickettsii in chicken embryo and L-929 cells in culture , 1976, Infection and immunity.

[7]  H. Winkler Rickettsial permeability. An ADP-ATP transport system. , 1976, The Journal of biological chemistry.

[8]  E. Weiss The biology of rickettsiae. , 1982, Annual review of microbiology.

[9]  T. Meyer,et al.  The repertoire of silent pilus genes in neisseria gonorrhoeae: Evidence for gene conversion , 1986, Cell.

[10]  Y. Rikihisa,et al.  Enzyme-linked immunosorbent assay for Potomac horse fever disease , 1987, Journal of clinical microbiology.

[11]  N. Saitou,et al.  The neighbor-joining method: a new method for reconstructing phylogenetic trees. , 1987, Molecular biology and evolution.

[12]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[13]  A. Azad,et al.  Infection of colonized cat fleas, Ctenocephalides felis (Bouché), with a rickettsia-like microorganism. , 1990, The American journal of tropical medicine and hygiene.

[14]  L. Poirier,et al.  Physiological methylation in carcinogenesis. , 1990, Progress in clinical and biological research.

[15]  P. Sharp,et al.  CODONS: a microcomputer program for codon usage analysis. , 1992, The Journal of heredity.

[16]  J. Sacci,et al.  Typhus and typhuslike rickettsiae associated with opossums and their fleas in Los Angeles County, California , 1992, Journal of clinical microbiology.

[17]  M. Fujioka Mammalian small molecule methyltransferases: their structural and functional features. , 1992, The International journal of biochemistry.

[18]  J. Palmer,et al.  Function and evolution of a minimal plastid genome from a nonphotosynthetic parasitic plant. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[19]  M. Polegre,et al.  Uptake and metabolism of S-adenosyl-L-methionine by Leishmania mexicana and Leishmania braziliensis promastigotes. , 1993, Molecular and biochemical parasitology.

[20]  D. Raoult,et al.  Genotypic identification and phylogenetic analysis of the spotted fever group rickettsiae by pulsed-field gel electrophoresis , 1993, Journal of bacteriology.

[21]  D. Raoult,et al.  Determination of genome size and restriction pattern polymorphism of Rickettsia prowazekii and Rickettsia typhi by pulsed field gel electrophoresis. , 1993, FEMS microbiology letters.

[22]  P. Renault,et al.  Gene inactivation in Lactococcus lactis: histidine biosynthesis , 1993, Journal of bacteriology.

[23]  P. Renault,et al.  Gene inactivation in Lactococcus lactis: branched-chain amino acid biosynthesis , 1993, Journal of bacteriology.

[24]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[25]  R. Fleischmann,et al.  The Minimal Gene Complement of Mycoplasma genitalium , 1995, Science.

[26]  N. Moran,et al.  Genetics, physiology, and evolutionary relationships of the genus Buchnera: intracellular symbionts of aphids. , 1995, Annual review of microbiology.

[27]  D. Stothard The evolutionary history of the genus Rickettsia as inferred from 16S and 23S ribosomal RNA Genes and the 17 kilodalton cell surface antigen gene , 1995 .

[28]  C. Kurland,et al.  Genomic evolution drives the evolution of the translation system. , 1995, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[29]  Manolo Gouy,et al.  SEAVIEW and PHYLO_WIN: two graphic tools for sequence alignment and molecular phylogeny , 1996, Comput. Appl. Biosci..

[30]  N. Moran Accelerated evolution and Muller's rachet in endosymbiotic bacteria. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[31]  R Staden,et al.  The staden sequence analysis package , 1996, Molecular biotechnology.

[32]  C. Kurland,et al.  The Rickettsia prowazekii genome: a random sequence analysis. , 1996, Microbial & comparative genomics.

[33]  D. Horne,et al.  Transport ofS-Adenosylmethionine in Isolated Rat Liver Mitochondria , 1997 .

[34]  J. Andersson,et al.  Genomic rearrangements during evolution of the obligate intracellular parasite Rickettsia prowazekii as inferred from an analysis of 52015 bp nucleotide sequence. , 1997, Microbiology.

[35]  D. Raoult,et al.  Rickettsioses as paradigms of new or emerging infectious diseases , 1997, Clinical microbiology reviews.

[36]  D. Petrov,et al.  Trash DNA is what gets thrown away: high rate of DNA loss in Drosophila. , 1997, Gene.

[37]  S. Salzberg,et al.  Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi , 1997, Nature.

[38]  D Graur,et al.  Patterns and rates of indel evolution in processed pseudogenes from humans and murids. , 1997, Gene.

[39]  C. dePamphilis,et al.  Evolution of plastid gene rps2 in a lineage of hemiparasitic and holoparasitic plants: many losses of photosynthesis and complex patterns of rate variation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[40]  K. Strimmer,et al.  Likelihood-mapping: a simple method to visualize phylogenetic content of a sequence alignment. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[41]  D Raoult,et al.  Citrate synthase gene comparison, a new tool for phylogenetic analysis, and its application for the rickettsiae. , 1997, International journal of systematic bacteriology.

[42]  T. Sicheritz-Pontén,et al.  The genome sequence of Rickettsia prowazekii and the origin of mitochondria , 1998, Nature.

[43]  C. Kurland,et al.  Reductive evolution of resident genomes. , 1998, Trends in microbiology.

[44]  N. Moran,et al.  Evolutionary rates for tuf genes in endosymbionts of aphids. , 1998, Molecular biology and evolution.

[45]  R. W. Davis,et al.  Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. , 1998, Science.

[46]  D. Petrov,et al.  High rate of DNA loss in the Drosophila melanogaster and Drosophila virilis species groups. , 1998, Molecular biology and evolution.

[47]  D. Petrov,et al.  Patterns of nucleotide substitution in Drosophila and mammalian genomes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[48]  C. Kurland,et al.  Molecular phylogeny and rearrangement of rRNA genes in Rickettsia species. , 1999, Molecular biology and evolution.