Research Topics

Archaea, Bioinformatics, Genomics, Host-Pathogen Interactions, Molecular Evolution

B.S. (Physics), University of California, Los Angeles, 1975
M.S. (Physics), University of California, Los Angeles, 1976
Ph.D. (Biophysics), University of Colorado Health Sciences Center, 1983
Postdoctoral (Molecular and Cellular Biology), National Jewish Hospital and Research Center, 1983-1984
Postdoctoral (Biology), Indiana University, 1984-1985
Assistant Scientist (Biology), Indiana University, 1985-1988

Video interview

The functions, evolutionary histories and structures of genes and proteins

Most of our research is based on genomics, with an emphasis on comparative genomics and genome evolution. Our approach is a combination of experimental work and computational analyses of genomes and proteins.

Comparative Genomics. We are participating with a wide range of research groups in the development of the SEED genome analysis environment, which is housed at Argonne National Laboratory. The SEED emphasizes the comparative analysis of genomes, and the ability to identify genes that are commonly clustered near one another in genomes. The SEED allows investigators to examine the phylogenetic distribution of any set of genes that is of interest to them, creating user-defined "subsystems". Using the curated genomic information of the SEED as a foundation, the RAST (Rapid Annotation using Subsystem Technology) genome annotation server has become one of the most commonly used tools in genome analysis. These data are also the basis of the genome annotations in PATRIC (Pathosystems Resource Integration Center).

Lateral gene transfer. One of the profound changes in biological thinking the past several years has been the growing appreciation of the role of lateral gene transfer in evolution. Although its role in the spread of antibiotic resistance was well known, genomic analyses reveal that most of the genes in a genome can be acquired by transfer. Even genes that could be inherited vertically (e.g., aminoacyl-tRNA synthetases) are still being passed between lineages at observable frequencies. We are characterizing the rates of transfer in a variety of lineages and on a variety of time scales. This will reveal the dynamics of the process and its role in both early and more recent evolution.

Bioinformatics. New research often requires new tools. The ability to extract information from genomes and gene sequences is limited by the existing set of analysis methods. One of our on-going activities is the development of new forms of data analysis. Past examples include contributions to phylogenetic analysis of nucleotide sequences and the identification of coding regions within a genome. Current efforts include better handling of sequence alignments and phylogenetic trees in an environment where sequence data increase incrementally (with each new genome), identification of laterally transferred genes, and analysis of pseudogene formation in Bacteria and Archaea.

An area of particular emphasis in the past several years has been the development of new tools for codon usage analysis. The genes in a genome display a wide variety of codon usages. The codon usages of vertically inherited genes reflect their level of expression, while the codon usages of horizontally acquired genes are commonly thought to reflect their source, and the amount of time since their transfer. We have developed tools to aid in automated identification of the predominant codon usages within each genome, and comparing them between genomes. More recent results indicate that the most recently acquired genes in genomes commonly have a distinctive codon usage, even though their origins appear to be closely related strains and species, which have codon usages that are similar to those of the recipient genome.

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