EVOLUTIONARY HISTORY OF THE MOUSE T COMPLEX--A MOLECULAR GENETICS APPROACH

小鼠T复合体的进化史——分子遗传学方法

• 批准号: 6239964
• 负责人: MARK A ERHART
• 金额: $ 20.84万
• 依托单位: CHICAGO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 1998-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6239964
• 关键词: Mus musculus; aggression; alleles; animal population genetics; biochemical evolution; chromosome aberrations; developmental genetics; gene expression; gene frequency; genetic library; genetic mapping; genetic recombination; genetic transcription; genome; lethal genes; molecular cloning; mutagens; nucleic acid sequence; phenotype; polymerase chain reaction; radiation genetics; restriction fragment length polymorphism; sex behavior

The t complex, a 20 cM region encompassing the proximal half of Chr 17 in house mice, offers unique opportunities for studying the origin and evolution of gene complexes, especially those that act as genetic parasites in the genome by preferentially transmitting themselves to the presumed detriment of the host. Additionally, the t complex harbors genes which influence mating behavior and aggression in mice, making it a model system for testing behavioral genetic hypotheses. Our previous work showed that many complete t haplotypes and many haplotypes in wild mice are combinations of t-specific and wild-type alleles. These wild- type alleles were confined to the distal portion of the t complex, suggesting that the nature of the chromosomal rearrangements and therefore the consequences of recombination differ between the proximal and distal portions of the complex. We propose to test several aspects of a hypothesis proposed to account for the origin and evolution of the t complex and to exploit the "mosaic" haplotypes to investigate several of these questions. The first goal involves estimating the relative ages of the four discrete portions of the complex through restriction fragment and sequence analysis of selected alleles, testing whether exceptional loci are confined to the distal portion of the t complex, and characterizing partial t haplotypes in wild mice. The second goal involves identifying functional genes within the t complex which may contribute to the critical phenotypes conferred by t haplotypes, i.e., transmission ratio distortion, male sterility, and embryonic lethality. This will be accomplished by selective cloning of t segments, examining transcription profiles of candidate genes, and identifying candidate genes in Mus spretus, a wild mouse species that has a gene arrangement on Chr 17 that is similar to part of the t complex. The third goal is to define the gene(s) within the t complex that are responsible for the well-defined mating behavior and aggression of mice harboring the t complex. This will be achieved through a combination of molecular analysis of semi-natural mouse populations, mapping recombination breakpoints in congenic laboratory mice, and the isolation of region- specific cloned segments from a congenic mouse library. All three goals are interrelated in that pursuing them will help to build a cohesive model of how the accumulation of specific mutations in Chr 17 genes helped to shape a genomic region that has propagated itself over the last 2 million years to the extent that over 25% of wild mice worldwide now possess this chromosomal variant.

t 复合体，一个 20 cM 的区域，包含 Chr 17 的近半部分 在家鼠中，为研究起源和 基因复合体的进化，特别是那些充当遗传基因的复合体 基因组中的寄生虫通过优先将自身传播到 推测对宿主造成损害。 此外，t 综合大楼还设有 影响小鼠交配行为和攻击行为的基因，使其 用于测试行为遗传假设的模型系统。 我们之前的 工作表明，许多完整的 t 单倍型和许多野生单倍型 小鼠是t特异性和野生型等位基因的组合。 这些野生的—— 型等位基因仅限于 t 复合体的远端部分， 表明染色体重排的性质和 因此重组的结果在近端之间是不同的 和复合体的远端部分。 我们建议从几个方面进行测试 提出一个假设来解释事物的起源和演化 t 复合体并利用“马赛克”单倍型来研究几种 这些问题。 第一个目标涉及估计相对年龄 通过限制性片段分析复合物的四个离散部分 并对选定的等位基因进行序列分析，测试是否异常 位点仅限于 t 复合体的远端部分，并且 表征野生小鼠的部分 t 单倍型。 第二个进球 涉及识别 t 复合体中的功能基因，这可能 有助于由 t 单倍型赋予的关键表型，即 传动比畸变、雄性不育和胚胎致死。 这将通过选择性克隆 t 片段、检查 候选基因的转录谱，并识别候选基因 Mus spretus 中的基因，一种具有基因排列的野生小鼠物种 位于 Chr 17 上，与 t 复合体的一部分相似。 第三个目标是 定义 t 复合体中负责的基因 携带 t 的小鼠明确的交配行为和攻击性 复杂的。 这将通过分子组合来实现 半自然小鼠群体分析，图谱重组 同源实验室小鼠的断点以及区域的分离 来自同源小鼠文库的特定克隆片段。 全部三个进球 是相互关联的，因为追求它们将有助于建立一个有凝聚力的 Chr 17 基因中特定突变如何积累的模型 帮助塑造了一个在过去自我繁殖的基因组区域 200万年前，目前全世界超过25%的野生老鼠 拥有这种染色体变异。