Porphyromonas gingivalis

  Proteome and Gene Cluster Comparisons  

Gene cluster comparison of distantly related Porphyromonas gingivalis and Chlamydia genomes

Until such time as the Bacteroides fragilis genomic sequence becomes available, chlamydial species offer some of the closest and potentially informative sequence comparisons with P.gingivalis. Both C. trachomatis and P.gingivalis are obligate anaerobes implicated in periodontal disease. C.pneumoniae and P.gingivalis especially are being investigated for their possible roles in atheromatous plaque formation.

Some references pertaining to these issues are:
Reed SG, Lopatin DE, Foxman B, Burt BA. Oral Chlamydia trachomatis in patients with established periodontitis. Clin Oral Investig. 2000 Dec;4(4):226-32. PMID: 11218493
Haraszthy VI, Zambon JJ, Trevisan M, Zeid M, Genco RJ. Identification of periodontal pathogens in atheromatous plaques. J Periodontol. 2000 Oct;71(10):1554-60. PMID: 11063387
Chiu B. Multiple infections in carotid atherosclerotic plaques. Am Heart J. 1999 Nov;138(5 Pt 2):S534-6. PMID: 10539867
Viale AM, Arakaki AK, Soncini FC, Ferreyra RG. Evolutionary relationships among eubacterial groups as inferred from GroEL (chaperonin) sequence comparisons. Int J Syst Bacteriol. 1994 Jul;44(3):527-33. PMID: 7520741

BLAST comparison of distantly related Porphyromonas gingivalis and Chlamydia genomes

In the BLAST comparisons presented here, each protein in the Porphyromonas gingivalis proteome is used as a query against the entire Chlamydia trachomatis and Chlamydia pneumoniae proteome and vice versa to find similar proteins in the compared genome. For each protein, the best hit, or the most similar match, to a protein in the other proteome is recorded. "Best hit" depends on the E-value, a measure of the probability that the observed level of similarity between two compared proteins could be due to chance alone. Thus, an E-value approaching 0 means there is "zero probability" that the protein's goodness-of-match to another protein can be attributed to chance. Examples of matches with excellent and marginal E-values are here.

Unique genes

Unique genes have no significant similarity to genes in the compared genome, as determined by the E-value. If the E-value of the best hit is greater than 0.0001, the query protein is considered unique.  Comparisons depicting unique genes are significant because they reveal the genes that are likely to be responsible for the biology, virulence, and pathogenicity unique to the bacterium (Kalman et al., Nature Genetics 21:385-389, 1999). In addition, this analysis suggests how closely the two genomes are phylogenetically related; a low proportion of unique genes suggests a close phylogenetic relationship. In rare instances, however, homologs can produce blast E-values less than 0.0001.

We have tabulated the unique proteins in each of the two proteomes:

P. gingivalis vs C.trachomatis at Pcut=0.0001

P. gingivalis vs C.pneumoniae at Pcut=0.0001

P. gingivalis vs C.trachomatis at Pcut=1e-7

P. gingivalis vs C.pneumoniae at Pcut=1e-7

Orthologous genes

W-H Li in his book Molecular Evolution (Sinauer Associates, Inc. Sunderland, Massachusetts) gives a succinct definition of orthologous and paralogous genes: "Two genes are said to be paralogous if they are derived from a duplication event, but orthologous if they are derived from a speciation event." Further details here.

Determining orthology is also significant in assessing the relationship between two genomes. Revealing which orthologous regions are conserved throughout evolution suggests the significance of those regions to the survival of the bacterium (Siefert et al., J Mol Evol 45:467-472, 1997). This type of analysis helps to resolve what sort of changes have occurred in one genome relative to the other throughout evolution, and also suggests the phylogenetic relationship between the bacteria. For example, a high proportion of orthologs suggests a close phylogenetic relationship (Watanabe et al., J Mol Evol 44(Suppl 1):S57-S64, 1996).

We have tabulated the common proteins in both of the two proteomes:

P. gingivalis vs C.trachomatis at Pcut=0.0001

P. gingivalis vs C.pneumoniae at Pcut=0.0001

P. gingivalis vs C.trachomatis at Pcut=1e-7

P. gingivalis vs C.pneumoniae at Pcut=1e-7

We have tabulated the common proteins in both of P. gingivalis vs C.trachomatis proteomes, but not in C.pneumoniae:

We have tabulated the common proteins in both of P. gingivalis vs C.trachomatis proteomes, but not in E.coli:

Distributon of unique and orthologous (common) genes based on the COG functional categories

Gene cluster comparison of distantly related Porphyromonas gingivalis and Chlamydia genomes

Finding clusters of genes common to multiple organisms may be informative for several reasons. First, it helps to identify potential operons. Operons contain related genes and regulatory signals (these signals are not addressed in this analysis). As discussed by Lodish et al, "genes encoding enzymes involved in related functions generally are located next to eachother in bacterial chromosomes. The genes in this cluster comprise a single transcription unit referred to as an operon. The full set of genes is transcribed from the first gene in the cluster to the last gene in the cluster, producing a single ("polycistronic") mRNA molecule. Ribosomes initiate translation at the beginning of each of the genes in this mRNA, producing multiple polpeptides. (Lodish, H., Baltimore, D., Berk, A., Zipursky, S. L., Matsudaira, P., and Darnell, J. Molecular Cell Biology, 3 ed. American Scientific Books. New York (1995). p 308.) Note that our analysis currently does not limit the genes within a cluster to one direction.

Positions of conserved clusters can be compared between genomes to establish phylogenetic relationships and mechanisms of evolutionary change between organisms. If the positions of clusters are very similar, the two organisms may be closely related; if the positions are dissimilar, the two organisms may be distantly related. Also, a map of the relative positions of conserved clusters my yield a pattern that reveals the mechanism of evolutionary divergence, such as insertions and deletions. We have compared the positions of clusters in P. gingivalis to numerous bacteria of varying phylogenetic relationships.

In addition, as with the analysis of any orthologous genes, the common clusters revealed can be compared with other genomes to determine if they are highly conserved (found in many bacteria), and, therefore, if they are necessary to perform certain functions for the survival of the bacterium.