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机制。该项目旨在测试一个新的模型，该模型表明显性负表型阻止新复制基因的错义突变的固定，从而延长其存活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8种哺乳动物基因组中核糖体蛋白基因的综合进化史，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重复序列的计算分析来测试一系列离散的进化预测。更广泛的影响：这项工作的更广泛的影响将体现在将遗传概念转化为K-8课堂，为高中生调整计算生物学研讨会，并通过东北联盟为代表性不足的少数民族和康涅狄格大学荣誉计划的暑期研究项目指导本科生研究。这些推广活动将提供可供全国教师使用的课程计划，并将在学生学术发展的关键和形成时期向他们介绍科学，并将帮助吸引年轻学生、未被充分代表的少数民族和妇女从事科学事业。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和实验生物学多学科研究训练机会。

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.