Collaborative Research: Developing a probabilistic model for gene family evolution

合作研究：开发基因家族进化的概率模型

• 批准号: 1515691
• 负责人: David Liberles
• 金额: $ 7.23万
• 依托单位: Temple University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-10-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1515691&HistoricalAwards=false
• 关键词: Collaborative; Research; Developing; probabilistic; model

Accurately estimating the timing and mode of gene duplications along the evolutionary history of species can provide invaluable information about the underlying mechanisms by which the genomes of organisms evolved and the genes with novel functions arose. The major challenge is the lack of an appropriate modeling framework for gene family evolution. To address this challenge, the investigators develop a probabilistic model for gene family evolution that is able to describe the relationship between the history of a gene family and the history of species by taking into account the effects of different evolutionary mechanisms of gene retention (neofunctionalization, subfunctionalization, dosage balance). The model involves two stochastic processes - a non-homogeneous birth and death process and a mutation process. The probability distribution of a gene family tree given the species tree is derived from a non-homogeneous birth and death process in which a hazard function is employed for modeling the loss rate associated with different evolutionary mechanisms. The probabilistic model provides a systematic way of handling the estimation error of gene family trees when analyzing gene family data and is thus able to more accurately estimate the gene duplication and loss events along the phylogeny of species.Advanced biotechnologies provide a vast amount of genetic data for the studies on gene family evolution. The main goal of the project is to develop a probabilistic model for gene family evolution, which can be used to effectively analyze gene family data. Gene duplication is the major resource of evolution novelty and plays an important role in gene family evolution. Thus this project will significantly advance our understanding on the process and biological consequences of gene duplication. As gene duplication played a pivotal role in evolution, the outcomes of the project will have significant impacts and important applications on a variety of fields, including evolutionary biology, phylogenetics, and cancer genetics that are closely related to human health and medicine.

准确估计沿着物种进化历史的基因复制的时间和模式可以提供关于生物体基因组进化和具有新功能的基因出现的潜在机制的宝贵信息。主要的挑战是缺乏一个合适的基因家族进化的建模框架。为了应对这一挑战，研究人员开发了一种基因家族进化的概率模型，该模型能够通过考虑基因保留的不同进化机制（新功能化，亚功能化，剂量平衡）的影响来描述基因家族历史与物种历史之间的关系。该模型涉及两个随机过程-非齐次生灭过程和突变过程。从一个非齐次的出生和死亡过程，其中的风险函数用于建模与不同的进化机制的损失率的基因家谱的概率分布的物种树。概率模型为基因家族数据分析提供了一种系统的处理基因家族树估计误差的方法，从而能够更准确地估计物种进化过程中沿着的基因重复和丢失事件。该项目的主要目标是开发一个基因家族进化的概率模型，该模型可用于有效地分析基因家族数据。基因复制是进化新奇的主要来源，在基因家族进化中起着重要作用。因此，该项目将大大促进我们对基因复制过程和生物学后果的理解。由于基因复制在进化中起着关键作用，该项目的成果将对与人类健康和医学密切相关的进化生物学、遗传学和癌症遗传学等多个领域产生重大影响和重要应用。