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.

Overwhelming evidence supports the endosymbiosis theory that mitochondria originated once from within a specific group of bacteria called α-proteobacteria. However, it is still not clear which bacterial species are its “first cousins”. Placing mitochondria correctly within the bacterial branch of tree of life is of great importance for elucidating the origin and early evolution of mitochondria and eukaryotes. It would shed light on many fascinating questions: What did mitochondrial ancestor do? What was its genetic make-up? What was the driving the initial endosymbiosis. To gain more insights into these exciting questions and better pinpoint the origin of mitochondria, we sequenced 18 bacterial endosymbionts that are close to mitochondria. Using phylogenomic methods, we reconstructed the genetic make-up of the mitochondrial ancestor. Surprisingly, our analyses indicate that mitochondrial ancestor was most likely an energy parasite that stole ATP from the host cell, a far cry from modern mitochondria as the powerhouse of the eukaryotic cell.   [Read more]          

Human Gut Microbiome

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.

Reconstructed metabolism of mitochondrial ancestor

The human gut microbiome contains hundreds of bacterial species and trillions of bacterial cells. These microbes play important roles in human biology including metabolism, modulation of the immune system, and pathogen resistance. Stability of the gut microbial community is critical for human health and well-being, as unbalanced gut microbiomes have been linked to a growing number of diseases such as diabetes, obesity, Clostridium difficile infection. We are interested in determining factors that shape the structure of gut microbial community. We are also interested in developing tools and methods to model the dynamics of gut microbial community, with the ultimate goal of precisely manipulating the gut microbiome to improve human health.