Population & Evolutionary Genomics - Projects
Evolution of Eukaryotic Parasites
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
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.
Evolution of Diversity in Microbial Pathogen Populations
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
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.
Genomic analysis of the biocontrol agent Lysobacter enzymogenes
Genomic analysis of the biocontrol agent Lysobacter enzymogenes. The genomic analysis of Lysobacter enzymogenes is a collaborative effort with Donald Kobayashi, Ph.D., from Rutgers University. This rapidly emerging bacterium is of major ecological and agricultural relevance. Known primarily as a prolific producer of enzymes and antibiotics, such as ß-lactams containing substituted side chains, macrocyclic lactams and macrocyclic peptide antibiotics, the species is gaining recognition for a number of novel features stemming from its ecological diversity, industrial applications, and most notably, unique biotic interactions. Lysobacter spp. genomes consist of relatively high G+C content typically ranging between the 65-72%. The group is regarded as a rich source for production of novel antibiotics. The feature of gliding motility alone has piqued the interest of many, since the role of gliding bacteria in soil ecology is poorly understood. In addition, while a number of different mechanisms have been proposed for gliding motility among a wide range of bacterial species, the genetic mechanism in Lysobacter remains unknown. Recent studies indicate L. enzymogenes is capable of establishing unique pathogenic interactions with a broad range of hosts that include lower plants and microbial eukaryotic hosts. This promiscuous behavior provides a unique opportunity to establish L. enzymogenes as a model organism for pathogenic interaction studies with lower organisms. Availability of the genome sequence of L. enzymogenes will provide insights into the general biology, parasitic lifestyle and biological control capacity of the organism. This project is funded under the U.S. Department of Agriculture Microbial Genome Sequencing Program (USDA-CRESS).