David A. Liberles
Laramie, WY 82071
As species diverge, specific molecular changes drive phenotypic changes and ultimately adaptation. Understanding the mechanism of the evolution of new functionality in genomes and how this correlates with the phenotypic divergence of species is the central theme of my research group.
Important genomic events include horizontal transfer, gene duplication, sequence divergence, gene expression divergence, mRNA splicing pattern divergence, and a host of other mechanisms. Detecting and collating these different events in a phylogenetic perspective is an ongoing process. This involves methods development, both at the DNA and protein sequence levels using model-based approaches, at protein structural levels, and at systems network levels.
One example of the application of these methods is the development of The Adaptive Evolution Database (TAED), which is now funded by NSF. This database includes information on protein coding sequences that appear to be undergoing adaptive evolution or changes of function along specific branches of the tree of life and has been established in a phylogenetic context. This database is a resource for asking the question, "What are the genes or molecular events that diverged as different species separated from a common ancestor?". The computational problem of gene tree-species tree reconciliation has become of interest in this context.
TAED and gene family evolution in general are also useful in combination with the Protein Data Bank (PDB) for analyzing the effect of protein structure and folding on the fixation of mutations during evolution. At the same time, we are also modeling the evolution of proteins to see how well our models explain observed genomic data. In addition to understanding how structure constrains evolution, we are also interested in how evolution constrains biologically observed protein structures (folds).
Specific examples of proteins are also of interest. These are studied computationally by examining substitutional patterns in a phylogenetic perspective and comparing that with three dimensional protein structures and literature mutagenesis studies to develop models for the roles of specific mutations in functional adaptation (for example in carbamoyl phosphate synthetase and in deoxyribonucleoside kinase). Other proteins of interest are studied further through experimental analysis coupled to phylogenetic analysis (for example plasminogen activator and myostatin). Myostatin has become a major protein of interest in our group as a model system for positive selection (ruminants) and for retention and functional divergence after gene duplication (salmon).
This research paradigm fits together at the interface of several fields, enabling us to address basic questions in biology and evolution. An understanding of the role of specific molecular processes underlying phenotypic effects allows us to better understand the evolution of species.
In the future, group software for download will be linked here.
Some useful links