Evolution of Eukaryotic Parasites
Investigator:
The phylum Apicomplexa comprises a diverse group of unicellular, eukaryotic parasites, many of which infect humans, or mammalian species on which human livelihood greatly depends. This phylum includes the causative agents of malaria, babesiosis, cryptosporidiosis, and toxoplasmosis in humans, as well as theileriosis and East Coast fever in cattle. The genome sequence for over a dozen apicomplexan species is available in either complete of draft form, including those of eight Plasmodium species, and three species of each in the Theileria, Babesia and Cryptosporidium genera.
Comparative genomic analyses of these genomes enables
scientists to study the genetic correlates of pathogenicity and disease. In
addition, several characteristics of these genomes, such as their small size,
high gene density and lack of transposable genetic elements, make
apicomplexasan ideal system to study the evolution of eukaryotic genomes.
Interdomain Lateral Gene Transfer
Investigator:
Lateral gene transfer (LGT) is a widely recognized mechanism for acquiring novel gene functions in bacteria. Its role in eukaryotes is unclear, and the role of bacterial DNA in the process even less clear. Until recently only a few instances of LGT to multicellular eukaryotes were described. Yet our studies indicate that >70% of sequenced organisms infected with Wolbachia bacteria have LGT from the bacterial endosymbiont genome to the animal host genome. Once transferred, some DNA is transcribed possibly facilitating acquisition of novel gene functions.
Since Wolbachia reside in the host's eggs and sperm, the high frequency of inherited LGT is not surprising. However, is this limited to just Wolbachia? A careful examination of a variety of endosymbiont-infected arthropod genome sequencing projects should shed light on any correlation between endosymbiont niche and LGT frequency. Is non-inherited LGT equally important? The bacteria Agrobacterium tumefaciens causes crown gall disease in infected plants through LGT of a pathogenic plasmid. We hypothesize that human symbionts or pathogens could cause similar diseases through non-inherited LGT. However, in order to detect such events, large eukaryotic genome projects must be extensively and carefully searched with large numbers of bacterial genomes.
Genomics and Population Genomics of Ixodes scapularis
Investigators:
The most significant vector of tick-borne diseases in the United States is the blacklegged tick Ixodes scapularis. I. scapularis transmits multiple zoonotic pathogens including Borrelia burgdorferi (Lyme disease, LD), Anaplasma phagocytophilum (human granulocytic anaplasmosis), Ehrlichia chaffeensis (human monocytic ehrlichiosis), Babesia microti (babesiosis), and Powassan encephalitis flavivirus (POW, tick-borne encephalitis). With the draft sequence of I. scapularis publicly available on Vectorbase and Genbank, it is now possible to mine the shotgun data for SNPs that can be used for studies characterizing the population and evolutionary genetics of this epidemiological important vector. We are combining available bioinformatic and genomic resources with field sampling and molecular techniques to (1) computationally identify SNPs in the genome, (2) validate their presence in field populations of Ixodes scapularis, and (3) use these SNPs to answer questions about the evolution of genes in I. scapularis populations.
Plasmid Evolution and Antimicrobial Resistance
Investigator:
In the emergence and spread of bacterial phenotypes, plasmids play a crucial role. As part of the horizontal gene pool, they are often shared between bacterial hosts and serve as genetic scaffolds for the acquisition, modification and recombination of horizontally transferred genetic elements. The transferability of many broad host range plasmids across strain and species borders allows for the accelerated dissemination of phenotypes under strong selection within bacterial communities. For example, plasmid transfer is being held responsible for the rapid spread of antibiotic resistance phenotypes between bacterial populations from environmental, agricultural and clinical settings. In many pathogens, such as the enteric species Escherichia coli and Salmonella enterica, plasmid-encoded virulence factors are often also plasmid-encoded, which in some cases has lead to the genetic linkage of antimicrobial resistance genes and human virulence factors on the same transferable plasmid type.
We are interested in analyzing the dynamics of plasmid-mediated genome evolution in bacteria, especially as it relates to antimicrobial selection. What is the diversity of plasmid types or scaffolds that exist in microbial populations from environmental, agricultural or clinical settings? Are there differences between those settings? How frequent is the exchange of plasmids between these settings? How does exposure to antibiotic resistant bacteria from food or other environmental sources affect the human microbiome, i.e. the collectivity of microbial species associated with the human body? How do plasmid populations change in response to antimicrobial selection, e.g. through antimicrobial treatment or prevention in human or veterinary medicine, agricultural use of antibiotics as growth-promoting factors or low exposure to traces of antimicrobials through food and water? Could more virulence-related phenotypes be genetically linked to antimicrobial resistance, creating a co-selection for virulence through antibiotic use? How could we restrict the further spread of plasmid-mediated antimicrobial resistance?
Evolution of Diversity in Microbial Pathogen Populations
Investigators:
The use of sequencing or chip-based genomic approaches makes it possible to gain insights into the genetic diversity and genome dynamics of bacterial pathogen populations. We study Yersinia pestis, Escherichia coli O157:H7 and diverse Bacillus and Chlamydia species as model systems, all of which have several representative in-house sequenced genome sequences available. A comparative analysis of these populations allows to analyze the types of host variation, selection and adaptation occurring during the time course of a single or multiple outbreaks of human disease and further to elucidate common and unique traits in genome evolution and speciation. To study these subtle but important genetic variations, we have developed a bioinformatics pipeline that facilitates the discovery and validation of rare polymorphisms taking into account the respective genome sequence read coverage and quality. Applying single nucleotide polymorphism (SNP)-based genotyping and re-sequencing methodologies, we are able to reconstitute a detailed evolutionary history of these microbial pathogens and resolve their genetically highly homogenous population structures. Studying the pan-genome, the global gene reservoir of the species, led to an estimate of the degree of reductive evolution and the extent of influx of genetic material via horizontal gene transfer, which aids in the definition of more accurate genetic species borders. The discovery of such genetic alterations in these dynamic bacterial pathogen populations can therefore provide insights into the genome evolution as well as the individual pathogenic potential critical for future forensic, diagnostic and epidemiological studies.
Genome Evolution and Pan-Genome Structure in Bacillus
Investigators:
Most of the aerobic Gram-positive spore-forming bacteria were originally placed in the genus Bacillus. As a result, it is a very diverse genus consisting of at least six clades and GC-content ranging from 33-64%. The sequencing of several Bacillus genomes has been completed in the last few years, but has mainly covered genomes of the pathogenic Bacillus thuringiensis-anthracis-cereus group or those closely related to B. subtilis. The ancient nature of B. megaterium makes it of particular importance in understanding the genome evolution, genome dynamics and speciation in Bacillus. The aim of this genomic study is to catalogue the genomic inventory of B. megaterium strain QMB1551 that carries an array of seven plasmids, and the naturally plasmidless isolate DSM319, to study the Bacillus biology through in-depth comparative genomics. The simultaneous sequencing of two prominent B. megaterium strains, deeply rooted in the phylogeny, presents an unique opportunity to study the genomic plasticity and genome evolution of the Bacillus group of organisms and can help to identify unique genetic traits not previously seen in Bacillus. Using the whole genome data of both genomes will allow to predict the species pan-genome and the extent of exchange of genetic material. The potential dissemination of genetic information between chromosomes and plasmids and to other members of the Bacillus group leads to a generation of unique genotype and phenotypes that might be relevant for species-specific niche adaptations.
