The funded research aims to provide practical tools for biologists who use cross-species comparisons to identify significant functional, ecological, or historical factors shaping the patterns of diversity among species. For example: is the evolution of HIV virulence related to rates of transmission among hosts? Which environmental factors most strongly influence the rate of evolution, and what are the strengths and directions of evolution? This broad class of questions all involve adaptive evolution (i.e., the direction and strength of natural selection). All existing methods share the significant shortcoming in using a completely neutral model of evolution. That is, previous methods fail to account for natural selection, despite the fact that it is the central feature of interest. The method developed here is the most comprehensive to date. It simultaneously accounts for random evolutionary fluctuations (such as genetic drift), common ancestry, and natural selection (under multiple adaptive regimes). Methods are provided for formulating scientific hypotheses as explicit mathematical models, each of which can then be fit to the data. Modern model-selection theory is then to identify the best-support model or models. Because in this approach, the causal factors of interest are explicitly modeled and tested directly against data, scientists will be able to use these methods to identify which aspects of the evolutionary process are most important, describe the relative strengths and directions of these evolutionary forces, and understand how they have influenced the tempo and mode of evolution.
The comparative method is a fundamental tool in organismal, evolutionary and ecological biology. It is used to identify and study the factors which have been important in producing the diversity of life we see today. Understanding the significant environmental, functional, and genetic mechanisms operative in the past is critical for planning conservation strategies for the future. It is also important in planning effective strategies to control human disease. For example, two fronts in the battle against HIV, predicting the spread of drug-resistance and immune-escape mutations, rely on an understanding of how HIV evolves in response to natural selection and how HIV evolution differs within and among hosts. Beyond the environmental sciences, it is now widely appreciated that studies of function (at the organismal, biochemical, or gene level) require the application of the comparative method.The funded research will provide practical tools to enable comparative biologists to make stronger tests of their hypotheses.
