Yeast as a model for understanding heterosis

本课题以面包酵母Saccharomyces cerevisiae为模式生物，研究杂种优势（杂种比亲本表现出更高活力的遗传现象）的遗传基础。杂种优势在作物育种中得到了广泛的应用，并在过去50年中为作物产量的重大提高做出了贡献。然而，它的遗传基础仍然难以捉摸，主要是因为缺乏一个强大的模式生物。本文提出S.酿酒酵母可以作为杂种优势的模式生物，有三个具体的目标。目的1建立酵母杂种优势的基本参数和模式。63株不同的S.根据它们的地理、遗传和环境来源选择酿酒酵母，并以所有成对组合进行杂交，以产生3906个杂交菌株。将测量这些亲本和杂交菌株的生长速率，并在三种生物学相关条件下量化杂种优势的普遍性和大小。杂种优势的概率和大小是否与亲本之间的地理、遗传和环境距离相关将被检验。将对所有63个亲本菌株的基因组进行测序，以便于解释观察到的杂种优势模式以及目标2和3。目的2定位杂种优势的数量性状基因座（QTL），并检验杂种优势的竞争模型（显性与超显性）。将回交与基于群体分离分析的极端QTL定位相结合，设计了一种定位杂种优势QTL和区分显性和超显性的有效策略。利用该方法对目标1中确定的5个杂种优势进行QTL定位。Aim 2中的定位允许将杂种优势的因果突变定位到1- 2kb的小基因组区域。在目标3中，将鉴定五个QTL的致病基因，并确认潜在的遗传机制（显性与超显性）。目的3将进一步鉴定致病突变，并研究杂种优势是否是由这些突变对蛋白质功能或基因表达的影响引起的。总之，该项目将为模式生物S的杂种优势模式和机制提供前所未有的大量信息。酿酒酵母和显着提高理解的神秘的，但高度有用的遗传现象的杂种优势。该项目的广泛影响是多方面的。首先，该项目将大大加深对杂种优势机理的理解，这可能对作物育种和杂种优势的其他应用产生深远的影响。其次，该项目将产生63个高质量的酵母基因组序列资源，可用于解决广泛的科学问题。第三，PI在培训进化遗传学家方面有着出色的记录;该项目将允许在经典遗传学，基因组学和计算生物学方面培训一名博士后研究员和一名研究生，以及他们在遗传学和进化方面的概念发展。第四，PI通过密歇根大学暑期研究机会计划（SROP）培训学生，该计划为在其研究领域中代表性不足的优秀本科生提供进行深入研究的机会，为他们在博士学位中的高级研究做好准备。程序.该项目将使PI继续并扩大与SROP的合作，在遗传学和进化方面培训代表性不足的本科生。第五，研究成果将融入PI定期举办的讲座中，包括“遗传学导论”和“生态学与进化生物学顶级研讨会”的本科课程，“分子与基因组进化”的研究生课程以及不定期的公开讲座。

This project aims to understand the genetic basis of heterosis (a genetic phenomenon in which a hybrid demonstrates higher vigor than its parents) using the baker's yeast Saccharomyces cerevisiae as a model organism. Heterosis is widely applied in crop breeding and has contributed to major improvements in crop yields in the last 50 years. Yet, its genetic basis remains elusive, primarily because of the lack of a powerful model organism. Here it is proposed that S. cerevisiae be developed as a model organism for heterosis, with three specific aims. Aim 1 will establish the basic parameters and patterns of heterosis in yeast. Sixty-three diverse strains of S. cerevisiae have been chosen based on their geographic, genetic, and environmental origins, and have been crossed in all pairwise combinations reciprocally to generate 3906 hybrid strains. The growth rates of these parental and hybrid strains will be measured and the prevalence and magnitude of heterosis will be quantified in three biologically relevant conditions. Whether the probability and magnitude of heterosis are correlated with geographic, genetic, and environmental distances between parents will be tested. The genomes of all 63 parental strains will be sequenced to facilitate the interpretation of the observed patterns of heterosis and Aims 2 and 3. Aim 2 will map the quantitative trait loci (QTLs) underlying heterosis and test competing models of heterosis (dominance vs. overdominance). A powerful strategy to map the QTLs underlying heterosis and to differentiate between dominance and overdominance has been designed by combining backcrosses with the bulk-segregant-analysis-based extreme QTL mapping. QTLs for five heterotic hybrids identified in Aim 1 will be mapped by this method. The mapping in Aim 2 allows the localization of causal mutations of heterosis to small genomic regions of 1-2 kb. In Aim 3, the causal genes of five QTLs will be identified and the underlying genetic mechanisms (dominance vs. overdominance) will be confirmed. Aim 3 will further identify causal mutations and investigate whether heterosis is caused by the effects of these mutations on protein function or gene expression. Overall, the project will provide unprecedented amount of information on the patterns and mechanisms of heterosis in the model organism S. cerevisiae and significantly improve understanding of the enigmatic yet highly useful genetic phenomenon of heterosis. The broader impacts of the project are manifold. First and foremost, this project will significantly deepen the mechanistic understanding of heterosis, which is likely to have profound impacts on crop breeding and other applications of heterosis. Second, the project will produce the resource of 63 high-quality yeast genome sequences that can be used for addressing a wide array of scientific questions. Third, the PI has an excellent record of training evolutionary geneticists; this project will allow the training of a postdoctoral fellow and a graduate student in classical genetics, genomics, and computational biology, in addition to their conceptual developments in genetics and evolution. Fourth, the PI has trained students through the University of Michigan Summer Research Opportunity Program (SROP), which offers outstanding undergraduates underrepresented in their field of study the opportunity to conduct intensive research to prepare them for advanced studies in a Ph.D. program. This project will allow the PI to continue and expand the collaboration with SROP in training underrepresented undergraduates in genetics and evolution. Fifth, research findings will be integrated into the lectures that the PI regularly gives, including the undergraduate courses of "Introduction to Genetics" and "Capstone Seminars in Ecology and Evolutionary Biology", the graduate course of "Molecular and Genomic Evolution", and occasional public lectures.