Wu Lab
 

The Bacterial Tree of Life

Endosymbiosis and the Origin of Mitochondria

A key prerequisite for studying microbial evolution and diversity is the accurate determination of the evolutionary relationships among the organisms of  interest. The explosive growth of bacterial genomic sequences makes it possible to reconstruct the bacterial tree of life on the genome level. Such “genome trees” are fairly robust and offer an excellent alternative to the widely used 16s rRNA based phylogeny. We have developed a simple, fast and accurate method (AMPHORA) to automate the genome tree construction process. With the arriving of thousands of new genomes on the horizon, we’ll continually update the bacterial tree of life. We hope eventually this will lead us to a more robust, genome based microbial systematics.


Bacterial genome tree

  1. -  11/2012  1993 genomes

    FastTree: genometree1112.tre


  1. -  02/08  578 genomes

    Newick: genometree0208.tre

    PDF: genometree0208.pdf

           

Overwhelming evidence supports the endosymbiosis theory that mitochondria originated once from within a specific group of bacteria called α-proteobacteria. However, significant questions remain. Early studies based on a few genes placed the mitochondrial ancestor near the Rickettsia species, but this has been challenged by us and by other groups based on recent, genome-level phylogenetic analyses. Placing this ancestral bacterium correctly within the bacterial phylogenetic tree is of great importance for elucidating the origin and early evolution of mitochondria and eukaryotes. It would shed light on many fascinating questions: Was the mitochondrial ancestor free-living or an obligate intracellular symbiont? What was its genetic make-up? Was its genome complex or already streamlined? To gain more insights into these exciting questions and better pinpoint the origin of mitochondria, we’ll sequence a few bacterial endosymbionts that are close to mitochondria. In the long run, we hope this research would lead us toward a better understanding of the bacterial endosymbiosis in general.            

Microbial Ecology and Human Microbiome

Opportunities abound for applying genomics to the study of microbial ecology. Currently we’re collaborating with Dr. Sale and Dr. Winther in UVA School of Medicine to survey the microflora associated with adenoid in a case-control study to determine its role in the development of chronic otitis media. I am also collaborating with Dr. Sale to investigate the oral microbiota and its association with periodontal disease, and with Dr. Wendy Lynch at UVA to study how alcohol exposure impacts the gut microbial population.


Phylogenomics Methods and Tools

The explosive growth of sequence data from both metagenomic studies and genome sequencing projects presents both an opportunity and a challenge for the increased usage of protein sequences for phylogenetic inference (e.g., phylotyping). Despite its demonstrated usefulness, phylogenetic inference based on protein sequences has been limited in application, mainly due to the formidable technical difficulties inherent in this approach. In response, we have developed an automated method of phylogenomic analysis (AMPHORA) to remove the bottlenecks that had precluded large-scale protein-based phylogenetic inference (e.g., sequence alignment masking and trimming). We will continue to work in this area and develop new open-source methods and tools and offer them to the community to help analyze the massive amount of sequence data generated from genomic and metagenomic projects.

Molecular Basis of Bacterial Predation

Micavibrio aeruginosavorus is one of very few bacteria that are known to prey on other bacterial species. Like a vampire, Micavibrio attacks by leeching on the prey cells and sucking the life out of them. Since Micavibrio can selectively kill human pathogens including Pseudomonas aeruginosa that causes lung infections in cystic fibrosis patients, studying the Micavibrio-prey interaction not only helps us elucidate the molecular mechanism of the bacterial predation but also has the potential to move beyond basic research and develop Micavibrio into a “living antibiotic” to treat infectious diseases.  We sequenced the Micavibrio genome and we are in the process of elucidating the molecular mechanism of the Micavibrio-Pesudomonas interaction.  For more information, see “in the news section”.