Evolutionary Genomics and Population Genetics of Pathogenic Streptococci

Streptococci are a diverse group of bacteria, comprising over 60 species, and include taxa which are members of human and animal commensal microflora, as well a variety of significant human, zoonotic, and agricultural pathogens. Recent molecular phylogenies support several taxonomic divisions within the genus, including Pyogenes, Bovis, Mutans, Salivarius, Anginosus, and Mitis. The major human pathogens occur in the Pyogenes, Mitis and Mutans groups.

Our goal is to reach a thorough understanding of the molecular specifics correlated with adaptive differences within and between the pathogenic taxa of the genus Streptococcus. Towards this goal we will implement modern phylogenetic and population genetic principles and procedures in the analysis of comparative genome sequence data gathered from multiple strains of the same pathogenic species and from representative isolates of different species. We are particularly interested in the role of positive selection in the diversification of Streptococcus species and the different components of their genomes. Positive selection is the fixation of advantageous mutations driven by natural selection, and is the fundamental process behind adaptive changes in genes and genomes, leading to evolutionary innovations and species differences. Our central hypothesis is that many loci, sites within loci, and noncoding functional elements, identified as being under lineage specific, or positive selection pressure in our evolutionary analyses will be key loci involved in the colonization, persistence, survival, and propensity to cause disease in these pathogenic streptococci.

The aims of this proposal are to:

1. Generate and annotate genome sequence data for multiple species of Streptococcus within the Pyogenes, and Mutans groups, chosen such that they will yield various sister group comparisons involving important human pathogens;
2. Assess the role of positive selection and lateral gene transfer in the diversification of the genomes of the species within the three key pathogenic group of streptococci: Pyogenes, Mutans and Mitis;
3. Collect comparative genome sequence data across multiple strains of the important human pathogens Streptococcus agalactiae, and Streptococcus pneumoniae for the purpose of analyzing selection pressure and demographic history, employing new population genetic based methods developed by us and others;
4. Perform a comprehensive survey of noncoding functional elements in the Streptococcus Pyogenes, Mutans and Mitis groups;
5. Use the results arising from the selection analyses and identification of noncoding functional elements to create gene knockout and site specific mutants for the human oral pathogen Streptococcus mutans, and assay the phenotypic effects.

The fundamental data on comparative genomics and molecular adaptation arising from this project will contribute to the development of novel therapeutic and preventative strategies for pathogenic species of Streptococcus.

White Paper Access

The initial white paper submitted can be downloaded here. Since white papers are not always approved exactly as submitted, this document may not exactly describe the final form of the project. Please contact gsc@jcvi.org if you have any questions.