A Direct Modeling Approach for Phylogenetic Comparative Analysis

这项资助的研究旨在为生物学家提供实用的工具，帮助他们利用跨物种比较来确定影响物种多样性模式的重要功能、生态或历史因素。例如：HIV毒力的进化是否与宿主之间的传播率有关？哪些环境因素对进化的速度影响最大？进化的优势和方向是什么？这类广泛的问题都涉及适应性进化（即，自然选择的方向和强度）。所有现有的方法都有一个明显的缺点，那就是使用一种完全中立的进化模型。也就是说，以前的方法不能解释自然选择，尽管它是我们感兴趣的中心特征。这里开发的方法是迄今为止最全面的。它同时解释了随机进化波动（如遗传漂变）、共同祖先和自然选择（在多种适应制度下）。方法提供了制定科学假设作为明确的数学模型，其中每一个都可以适合于数据。现代模型选择理论的目的是确定一个或多个最佳支持模型。因为在这种方法中，感兴趣的因果因素被明确地建模并直接针对数据进行测试，科学家将能够使用这些方法来确定进化过程的哪些方面是最重要的，描述这些进化力量的相对优势和方向，并了解它们如何影响进化的速度和模式。比较方法是生物、进化和生态生物学的基本工具。它被用来识别和研究那些对我们今天所看到的生命多样性产生重要影响的因素。了解在过去起作用的重要的环境、功能和遗传机制对于规划未来的保护策略至关重要。它在规划控制人类疾病的有效战略方面也很重要。例如，防治艾滋病毒的两条战线——预测耐药性和免疫逃逸突变的传播——依赖于对艾滋病毒如何响应自然选择而进化以及艾滋病毒在宿主内部和宿主之间如何进化的理解。在环境科学之外，现在人们普遍认识到，功能研究（在有机体、生物化学或基因水平上）需要应用比较方法。资助的研究将提供实用的工具，使比较生物学家能够对他们的假设进行更有力的测试。

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.