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Variation in the Neisseria meningitidis FadL-like protein: an evolutionary model for a relatively low-abundance
Daniel Yero1, Caroline Vipond2, Yanet Climent1
1Department of Molecular Biology, Division of Biotechnology, Finlay Institute, Havana, Cuba.
Abstract:
The molecular diversity of a novel Neisseria meningitidis antigen, encoded by the ORF NMB0088 of MC58 (FadL-like protein), was assessed in a panel of 64 diverse meningococcal strains. The panel consisted of strains belonging to different serogroups, serotypes, serosubtypes and MLST sequence types, of different clinical sources, years and countries of isolation. Based on the sequence variability of the protein, the FadL-like protein has been divided into four variant groups in this species. Antigen variants were associated with specific serogroups and MLST clonal complexes. Maximum-likelihood analyses were used to determine the relationships among sequences and to compare the selection pressures acting on the encoded protein. Furthermore, a model of population genetics and molecular evolution was used to detect natural selection in DNA sequences using the non-synonymous : synonymous substitution (d(N) : d(S)) ratio. The meningococcal sequences were also compared with those of the related surface protein in non-pathogenic commensal Neisseria species to investigate potential horizontal gene transfer. The N. meningitidis fadL gene was subject to only weak positive selection pressure and was less diverse than meningococcal major outer-membrane proteins. The majority of the variability in fadL was due to recombination among existing alleles from the same or related species that resulted in a discrete mosaic structure in the meningococcal population. In general, the population structuring observed based on the FadL-like membrane protein indicates that it is under intermediate immune selection. However, the emergence of a new subvariant within the hyperinvasive lineages demonstrates the phenotypic adaptability of N. meningitidis, probably in response to selective pressure.
Insights
Molecular diversity of the Neisseria meningitidis FadL-like protein was analyzed in 64 strains, revealing four variants linked to serogroups and MLST types. This antigen shows weak positive selection and adaptability, indicating potential immune pressure and evolution within meningococcal populations.
Area of Science:
- Microbiology
- Molecular Evolution
- Population Genetics
Background:
- Neisseria meningitidis is a significant human pathogen.
- The FadL-like protein (encoded by ORF NMB0088) is a novel antigen with potential roles in pathogenesis.
- Understanding the molecular diversity of meningococcal antigens is crucial for vaccine development and epidemiology.
Purpose of the Study:
- To assess the molecular diversity of the Neisseria meningitidis FadL-like protein.
- To investigate the evolutionary pressures and population structure associated with this antigen.
- To compare the fadL gene diversity with other major outer-membrane proteins and related Neisseria species.
Main Methods:
- Analysis of the fadL gene sequence from 64 diverse Neisseria meningitidis strains.
- Classification of protein variants based on sequence variability.
- Phylogenetic analyses using maximum-likelihood methods.
- Detection of natural selection using the non-synonymous to synonymous substitution ratio (dN:dS).
- Comparison with homologous genes in commensal Neisseria species.
Main Results:
- The FadL-like protein exhibits molecular diversity, categorized into four variant groups.
- Antigen variants are associated with specific serogroups and MLST clonal complexes.
- The fadL gene is under weak positive selection and shows less diversity than major outer-membrane proteins.
- Recombination contributes significantly to fadL variability, creating a mosaic structure.
- Evidence suggests intermediate immune selection and phenotypic adaptability, with new subvariants emerging in hyperinvasive lineages.
Conclusions:
- The FadL-like protein is a diverse antigen in Neisseria meningitidis, with variants linked to epidemiological factors.
- Evolutionary analysis indicates weak positive selection and significant recombination shaping fadL diversity.
- The protein's adaptability suggests ongoing immune pressure and potential for rapid evolution in response to selective forces.
- These findings contribute to understanding meningococcal population dynamics and antigen evolution.
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