Project description:Group C Streptococcus dysgalactiae subsp. dysgalactiae (GCS) field strains causative of bovine mastitis and group C or group G Streptococcus dysgalactiae subsp. equisimilis (GCS/GGS) isolates from human infections were tested for the presence of virulence genes employing a microarray containing 220 virulence genes of S. pyogenes (GAS).
Project description:Encoded in the hundreds by the human genome, KRAB-containing zinc finger proteins (KRAB-ZFPs) constitute a rapidly evolving family of transcription factors with largely undefined functions. Here, by a combination of phylogenetic and genomic approaches, we retrace the evolutionary history of KRAB-ZFP genes and define the genomic targets of their human products. Through in silico analysis of 207 vertebrate genomes and chromatin immunoprecipitation / deep sequencing characterization of 257 human KRAB-ZFPs, we identify the root of the family in an early Devonian ancestor of tetrapods, describe its diversity amongst these species, and reveal that the majority of its human members primarily recognize transposable elements. Furthermore, by dissecting the timeline and modalities of interactions between human KRAB-ZFPs and their targets, we provide evidence strongly suggesting that these proteins, rather than just engaged in an evolutionary arms race against transposable elements, exploit these invaders as regulatory platforms for the benefit of the host.
Project description:Group A Streptococcus (GAS) has a rich evolutionary history of horizontal transfer among its core genes. Yet, despite extensive genetic mixing, GAS strains have discrete ecological phenotypes. To further our understanding of the molecular basis for ecological phenotypes, comparative genomic hybridization of a set of 97 diverse strains to a GAS pan-genome microarray was undertaken, and the association of accessory genes with emm genotypes that define tissue tropisms for infection was determined. Of the 22 non-prophage, accessory gene regions (AGRs) identified, only three AGRs account for all statistically significant linkage disequilibrium among strains having the genotypic biomarkers for throat versus skin infection specialist. Networked evolution and population structure analysis of loci representing each of the AGRs reveals that most strains with the skin specialist and generalist biomarkers form discrete clusters, whereas strains with the throat specialist biomarker are highly diverse. To identify co-inherited and co-selected accessory genes, the strength of genetic associations was determined for all possible pair wise combinations of accessory genes among the 97 GAS strains. Accessory genes showing very strong associations provide the basis for an evolutionary model, which reveals that a major transition between many throat and skin specialist haplotypes correlates with the gain or loss of genes encoding fibronectin-binding proteins. This study employs a novel synthesis of tools to help delineate the major genetic changes associated with key adaptive shifts in an extensively recombined bacterial species.
Project description:ZIKV strains belong to three phylogenetic lineages: East African, West African, and Asian/American. RNA virus genomes exist as populations of genetically-related sequences whose heterogeneity may impact viral fitness, evolution, and virulence. The genetic diversity of representative ZIKVs (N=7) from each lineage was examined using next generation sequencing (NGS) paired with downstream Shannon entropy calculation and single nucleotide variant (SNV) analysis. This comprehensive analysis of ZIKV genetic diversity provides insight into the genetic diversity of ZKIV and repository of SNV positions across lineages.
Project description:To test if scRNA-seq contains sufficient phylogenetic information to reconstruct a population history of cancer, immunosuppressed NU/J mice were injected with human cancer cells (MDA-MB-231-LM2). The tumors that develop are derived from the same population and thus share a common ancestor, but evolved independently in each mouse and should form separate clades on reconstructed phylogenetic trees when analysed together. We explore and compare results of phylogenetic analyses based on both expression levels and SNVs called from our scRNA-seq data. Both techniques are shown to be useful for reconstructing phylogenetic relationships between cells, refecting the clonal composition of a tumor. Without an explicit error model, standardized expression values appears to be more powerful and informative than the SNV values at a lower computational cost, due to being a by-product of standard expression analysis. Our results suggest that scRNA-seq can be a competitive alternative or useful addition to conventional scDNA-seq phylogenetic reconstruction. Our results open up a new direction of somatic phylogenetics based on scRNA-seq data. Further research is required to refne and improve these approaches to capture the full picture of somatic evolutionary dynamics in cancer.
