A Direct Modeling Approach for Phylogenetic Comparative Analysis

这项受资助的研究旨在为生物学家提供实用工具，他们使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：艾滋病毒毒力的演变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？这一大类问题都涉及适应性进化(即自然选择的方向和力度)。所有现有的方法都有一个显著的缺点，那就是使用完全中立的进化模型。也就是说，以前的方法未能解释自然选择，尽管它是人们感兴趣的核心特征。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(如基因漂移)、共同祖先和自然选择(在多个适应机制下)。提供了将科学假设表述为明确的数学模型的方法，然后每个模型都可以与数据相适应。现代模型选择理论则是确定最支持的一个或多个模型。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根据数据进行测试，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。比较方法是生物体生物学、进化生物学和生态生物学的基本工具。它被用来识别和研究在产生我们今天看到的生物多样性方面起到重要作用的因素。了解过去运行的重要的环境、功能和遗传机制对于规划未来的保护战略至关重要。在规划控制人类疾病的有效战略方面也很重要。例如，抗击艾滋病毒的两条战线，即预测抗药性和免疫逃逸突变的传播，取决于对艾滋病毒如何进化以响应自然选择的理解，以及艾滋病毒进化在宿主内部和之间的差异。除了环境科学之外，现在人们普遍认识到，对功能的研究(在有机体、生化或基因水平上)需要应用比较方法。资助的研究将提供实用工具，使比较生物学家能够对他们的假说进行更有力的测试。

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.