Independent evolution of the core and accessory gene sets in the genus Neisseria: insights gained from the genome of Neisseria lactamica isolate 020-06

Abstract

Background: The genus Neisseria contains two important yet very different pathogens, N. meningitidis and N. gonorrhoeae, in addition to non-pathogenic species, of which N. lactamica is the best characterized. Genomic comparisons of these three bacteria will provide insights into the mechanisms and evolution of pathogenesis in this group of organisms, which are applicable to understanding these processes more generally.

Results: Non-pathogenic N. lactamica exhibits very similar population structure and levels of diversity to the meningococcus, whilst gonococci are essentially recent descendents of a single clone. All three species share a common core gene set estimated to comprise around 1190 CDSs, corresponding to about 60% of the genome. However, some of the nucleotide sequence diversity within this core genome is particular to each group, indicating that cross-species recombination is rare in this shared core gene set. Other than the meningococcal cps region, which encodes the polysaccharide capsule, relatively few members of the large accessory gene pool are exclusive to one species group, and cross-species recombination within this accessory genome is frequent.

Conclusion: The three Neisseria species groups represent coherent biological and genetic groupings which appear to be maintained by low rates of inter-species horizontal genetic exchange within the core genome. There is extensive evidence for exchange among positively selected genes and the accessory genome and some evidence of hitch-hiking of housekeeping genes with other loci. It is not possible to define a 'pathogenome' for this group of organisms and the disease causing phenotypes are therefore likely to be complex, polygenic, and different among the various disease-associated phenotypes observed.

Figure 1

Genealogical relationships of Neisseria isolates inferred from 19 loci. CLONALFRAME trees were drawn from the sequences from 19 housekeeping gene fragments from 79 isolates. These include the eight complete Neisseria genomes, 20 isolates representing 20 unique seven locus STs (one ST from each clonal complex and two STs not belonging to clonal complexes) from the meningococcal collection used to validate the MLST scheme [29], and 51 N. lactamica isolates, comprising 46 unique seven locus STs sampled from a population used to analyse diversity in N. lactamica [30]. N. lactamica clonal complexes are circled. N. lactamica (Nla) = red, N. meningitidis (Nme) = blue, N. gonorrhoeae (Ngo) = green.

Figure 2

Comparisons of genome organization. 2A. A comparison between the genomes of N. meningitis Z2491 and N. lactamica 020-06 using ACT [46]. The apparent re-arrangement at the start of the Z2491 genome with respect to N. lactamica 020-06 was because the start of the Z2491 genome was not assigned at the origin of replication. 2B. A dot plot comparing the genome sequence of N. lactamica 020-06 with the seven other complete Neisseria genomes.

Figure 3

Percentage of CDSs in each classification category. * Data produced by comparing the genome of N. meningitidis Z2491 with the genomes of N. lactamica 020-06, N. meningitidis genomes MC58, FAM18, 053442, α14, and N. gonorrhoeae genomes FA1090 and NCCP11945. ** Data produced using the annotation from FAM18 and by comparing the genomes of N. lactamica 020-06, N. meningitidis genomes Z2491, MC58, FAM18, and N. gonorrhoeae genome FA1090. *** NCBI BLAST search 16-11-09. Nme = N. meningitidis, Nla = N. lactamica, Ngo = N. gonorrhoeae

Figure 4

The percentage identity of CDSs shared by N. meningitidis strain α14 and seven completely sequenced Neisseria genomes. Putative orthologues were identified by reciprocal-best-match FASTA searches between α14 and the amino acid sequences of the other genomes using cut-offs of 80% sequence length and 30% identity.