How clonal are Neisseria species? The epidemic clonality model revisited

Abstract

The three species Neisseria meningitidis, Neisseria gonorrheae, and Neisseria lactamica are often regarded as highly recombining bacteria. N. meningitidis has been considered a paradigmatic case of the "semiclonal model" or of "epidemic clonality," demonstrating occasional bouts of clonal propagation in an otherwise recombining species. In this model, occasional clonality generates linkage disequilibrium in the short term. In the long run, however, the effects of clonality are countered by recombination. We show that many data are at odds with this proposal and that N. meningitidis fits the criteria that we have proposed for predominant clonal evolution (PCE). We point out that (i) the proposed way to distinguish epidemic clonality from PCE may be faulty and (ii) the evidence of deep phylogenies by microarrays and whole-genome sequencing is at odds with the predictions of the semiclonal model. Last, we revisit the species status of N. meningitidis, N. gonorrheae, and N. lactamica in the light of the PCE model.T he clonality/sexuality controversy in microbiology has gone on for more than 35 y in bacteria (1, 2) as well as in parasitic protozoa (3-6). Early on, several instances of bacterial and parasitic species were removed from the clonal paradigm and instead were considered as "highly recombining" (5). The controversy now can be reconsidered in the light of major results obtained with modern technologies, such as whole-genome sequencing (WGS), single nucleotide polymorphism analysis (SNP), microarrays, and megacomputing, which have made possible considerable advances in evolutionary biology, population genetics, and molecular epidemiology. We reconsider the issue of the population structure of Neisseria meningitidis in the light of these advances.N. meningitidis and the "Epidemic Clonality" and "Semiclonal" Models The molecular epidemiology and population genetics of N. meningitidis, a major agent of meningitis, has received much attention. Thousands of strains have been characterized by various markers, including multilocus enzyme electrophoresis (MLEE), multilocus sequence analysis (MLST), random primed polymorphic DNA (RAPD), and WGS and SNP analysis (reviewed in ref. 7). Pioneering MLEE studies showed that, although this pathogen has a drastically restricted ecological niche, infecting only humans, it exhibits considerable genetic diversity, suggesting that N. meningitidis undergoes extensive genetic recombination. However, the natural populations of this species consistently exhibit a strong linkage disequilibrium (LD), i.e., nonrandom association between genotypes at different loci (8). To reconcile these two observations, which at first appear mutually inconsistent, Maynard Smith et al. (5) proposed the epidemic clonality model, which states that the species under study undergoes occasional bouts of clonal propagation in an otherwise recombining population structure. "Epidemic" clones, which are greatly favored by both positive and purging selection, are repeatedly represented in natural populations as ...

Genomic Investigation Reveals Highly Conserved, Mosaic, Recombination Events Associated with Capsular Switching among InvasiveNeisseria meningitidisSerogroup W Sequence Type (ST)-11 Strains

“…Dominance of single cps allelic type is consistent with the “genocloud” concept in which a set of mutually co-adapted sets of genes persist despite presence of a few, mostly transient, escape variants ( Gupta et al 1996 ; Zhu et al 2001 ). In general, DNA uptake sequences ( Duffin and Seifert 2010 ) and restriction modification systems ( Budroni et al 2011 ; Tibayrenc and Ayala 2015 ) are known to affect the rate, extent and donor specificity of recombination in Neisseria . However, the precise role of these factors in capsular switching is yet to be established.…”

Why should mitochondria define species?

“…Clonal outgrowth and replacement of the inoculating population was inferred from the earliest chemostat [124] as well as later serial transfer experiments [125]. Epidemiology shows that repeated bottlenecks play dominant roles in the natural evolution of microbial pathogens including protists, bacteria and viruses [126][127][128][129][130][131][132]. A visually impressive demonstration of successive clonal selection and population outgrowth is seen in time lapse studies of bacteria serially mutating to new heights of antibiotic resistance [133].…”

Response to Tibayrenc and Ayala: reproductive clonality in protozoan pathogens – truth or artefact?

“…This is a shame, as in our review, we set out to try and define some of the increasingly impenetrable lexicon developed by Tibayrenc and Ayala to describe PCE [e.g. (Tibayrenc & Ayala , , )]. Specifically, we attempted to define the meaning of the term ‘evolutionary scale’ as Tibayrenc and Ayala use it.…”

“…Careful reading of this commendable study (and personal correspondence with its authors) reveals precisely the pattern of population diversity we highlighted: deep subdivisions with little or no exchange between them; intense lateral exchange of genetic information within them. In still yet another recent review, Tibayrenc and Ayala conveniently dismiss this finding as 'invisible sex' (Tibayrenc & Ayala 2015a), regardless of the considerable genetic diversity present among strains involved and the possible fitness benefits associated (virulence factors, antimicrobial resistance, etc) [see also Table 1 in (Ramirez & Llewellyn 2014)]. Importantly, Budroni et al's findings absolutely contradict the expectations of Tibayrenc and Ayala's much discussed and little supported 'Russian doll' hypothesis [e.g.…”