The Evolution of Gene and Genome Architecture

智力价值：因为生物多样性的所有方面最终都来自DNA水平的资源，进化的机械论必须从基因组水平开始。这项工作侧重于这样一个假设，即基因组进化的许多方面是由非适应性力量(随机遗传漂移、突变和重组)驱动的，而不是由响应外部生态力量的自然选择驱动的。利用数学/计算分析，这项研究将利用全基因组测序项目提供的大量资源，从病毒到细胞器，再到细菌和多细胞物种。由于进化是一个种群水平的过程，将优先发展一种与公认的种群遗传学原理相一致的基因组进化的一般理论，同时跨越计算生物学和信息学、分子和细胞生物学以及系统生物学等领域。总体目标是帮助比较基因组学的描述领域转变为更具解释性的进化基因组学领域。在提出的假设下，作为多细胞物种标志的许多复杂基因组特征在很大程度上是选择效率大幅降低的结果，而微生物物种的简化基因组是高效选择的结果，反对积累具有突变危险的过剩DNA。至少，即将开发的理论为解释基因组复杂性的进化提供了一个零(非适应性)假设。更广泛的影响：通过整合这些不同的子项目，拟议研究的总体目标是帮助将比较基因组学的描述性领域转变为更具解释性的进化基因组学领域，并帮助发展最终将是出现进化细胞生物学领域所必需的智力基础设施。此外，该研究项目将与一系列教育目标交织在一起，包括：1)建立一套与基因组进化课程相关的年度项目，为来自生命科学和信息学的学生提供服务；2)招募对数学有兴趣的生物学本科生参加一个两到三年的研究计划；以及3)在资助参与者中发展一个类似培训拨款？的综合环境。

Intellectual Merit:Because all aspects of biodiversity ultimately derive from DNA-level resources, a mechanistic theory of evolution must start at the genomic level. This work focuses on the hypothesis that many aspects of genome evolution are driven by nonadaptive forces (random genetic drift, mutation, and recombination) rather than natural selection responding to external ecological forces. Using mathematical/computational analysis, the research will exploit the enormous set of resources available from whole-genome sequencing projects, from viruses to organelles to bacteria and multicellular species. Because evolution is a population-level process, priority will be on developing a general theory for genomic evolution consistent with well-established principles of population genetics, while spanning the fields of computational biology and informatics, molecular and cellular biology, and systems biology.The overall goal is to help transform the descriptive field of comparative genomics into a more explanatory field of evolutionary genomics. Under the proposed hypothesis, many of the complex genomic features that are the hallmark of multicellular species emerged largely as a consequence of a substantial reduction in the efficiency of selection, whereas the streamlined genomes of microbial species result from highly efficient selection opposing the accumulation of mutationally hazardous excess DNA. At the very least, the theory to be developed provides a null (nonadaptive) hypothesis for interpreting the evolution of genome complexity. Broader Impact: Through the integration of these various subprojects, the overall goal of the proposed research is to help transform the descriptive field of comparative genomics into a more explanatory field of evolutionary genomics, as well as to help develop the intellectual infrastructure that will ultimately be necessary for the emergence of a field of evolutionary cell biology. In addition, the research project will be intertwined with a set of educational goals, including: 1) the establishment of an annual set of projects associated with a genome evolution class that services students from both the life sciences and informatics; 2) the recruitment of mathematically inclined biology undergraduates into a two- to three-year research program; and 3) the development of an integrative ?training-grant?-like environment among the grant participants.