Gene Duplication in Ribosomal Protein Evolution

智力价值：理解基因组复杂性的进化是进化生物学中的一个主要挑战。三十多年来，基因复制一直被认为是复杂基因组进化的主要原料产生机制。该项目旨在测试一种新的模型，该模型认为显性负表型阻止了新复制基因中错义突变的固定，从而延长了它们的生存时间，并使新基因拷贝的功能进化成为可能。该模型将在核糖体蛋白基因家族中进行测试，并将重建八个哺乳动物基因组中核糖体蛋白基因的全面进化史，将通过体内功能分析测试该模型的关键预测，并将使用已知哺乳动物副本的计算分析来测试一系列离散的进化预测。更广泛的影响：这项工作的更广泛影响将体现在将遗传概念翻译到K-8课堂上，为高中生改造计算生物学研讨会，以及通过东北联盟针对代表性不足的少数族裔的夏季研究计划和康涅狄格大学荣誉计划指导本科生研究。这些推广活动将提供可供全国教师使用的教案，并将在学生学术发展的关键和形成时期向学生传授科学，并将有助于吸引年轻学生、代表性不足的少数群体和妇女投身科学事业。此外，拟议的研究项目将为本科生和研究生提供优秀的计算生物学和实验生物学多学科研究培训机会。

Intellectual Merit: Understanding the evolution of genome complexity is a major challenge in evolutionary biology. For over thirty years, gene duplication has been recognized as the major mechanism generating raw material for the evolution of complex genomes. This project is designed to test a new model that suggests that dominant negative phenotypes prevent the fixation of missense mutations in newly duplicated genes, thereby extending their survival and enabling the functional evolution of new gene copies. The model will be tested in the ribosomal protein gene family and will reconstruct the comprehensive evolutionary history of ribosomal protein genes in eight mammalian genomes, will test key predictions of the model through the in vivo functional analysis, and will test a collection discrete evolutionary predictions using computational analysis of known mammalian duplicates.Broader Impacts: The broader impacts of this work will be manifest in the translation of genetic concepts to K-8 classrooms, adaptation of computational biology workshops for high-school students, and mentored undergraduate research through the Northeast Alliance Summer Research Program for Underrepresented Minorities and the University of Connecticut Honors Program. These outreach initiatives will provide lesson plans that can be used by teachers across the country and will bring science to students at critical and formative times in their academic development and will help attract young students, underrepresented minorities and women to careers in science. In addition, the proposed research project will provide excellent multi-disciplinary research training opportunities in computational and experimental biology for undergraduate and graduate students.