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

t复合体，一个20 cM的区域，包括Chr 17的近端一半， 在家鼠中，为研究起源提供了独特的机会， 基因复合体的进化，特别是那些作为遗传因子的基因复合体。 基因组中的寄生虫通过优先将自己传播到 被认为是对主人的伤害。 此外，t复合体港口 影响老鼠交配行为和攻击性的基因， 一个测试行为遗传假设的模型系统。 我们以前的 结果表明，野生型中有许多完整的t单倍型， 小鼠是T特异性等位基因和野生型等位基因的组合。 这些野- 型等位基因局限于T复合体的远端部分， 这表明染色体重排的性质和 因此，重组的结果在近端之间不同， 和复合体的远端部分。 我们建议测试几个方面 一个假设提出来解释的起源和演变的 t复杂，并利用“马赛克”单倍型来研究几个 这些问题。 第一个目标是估计相对年龄 复合物的四个离散部分通过限制性片段 并对选定的等位基因进行序列分析， 基因座局限于t复合体的远端部分，并且 描述野生小鼠的部分t单倍型。 第二个目标 包括鉴定T复合体中的功能基因， 有助于由t单倍型赋予的关键表型，即， 传递率畸变、雄性不育和胚胎致死。 这将通过选择性克隆t片段， 候选基因的转录谱，并鉴定候选基因。 小家鼠（Mus spretus）的基因，一种野生小鼠， 在Chr 17上，类似于t复合体的一部分。 第三个目标是 为了确定t复合体中负责 明确定义的交配行为和侵略的小鼠窝藏的t 复杂. 这将通过结合分子 半天然小鼠种群分析，定位重组 同源实验室小鼠中的断点，以及区域- 从同类小鼠文库中克隆特定片段。 所有三个目标 是相互关联的，因为追求这些目标将有助于建立一个有凝聚力的 Chr 17基因中特定突变的积累模型 帮助塑造了一个基因组区域， 200万年前，全世界超过25%的野生老鼠 拥有这种染色体变异。

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.