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

T复合体，一个20厘米的区域，包围着Chr17的近半部分 在家中的老鼠中，提供了研究起源和 基因复合体的进化，尤其是那些起基因作用的基因 通过优先将自己传播到基因组中的寄生虫 推定对东道主不利。此外，t综合体还拥有 影响小鼠交配行为和攻击性的基因，使 一种用于测试行为遗传学假说的模型系统。我们以前的 研究表明，许多完整的t单倍型和许多野生单倍型 小鼠是t特有和野生型等位基因的组合。这些狂野的- 类型等位基因仅限于t复合体的远端部分， 这表明染色体重排的本质和 因此，重组的后果在不同的近端不同 以及建筑群的远端部分。我们建议测试几个方面 提出了一种假说来解释宇宙的起源和进化 T复合体，并利用“马赛克”单倍型来研究 这些问题。第一个目标涉及估计相对年龄。 通过限制性内切酶片段连接到复合体的四个离散部分中 并对选定的等位基因进行序列分析，测试是否存在异常 基因座被限制在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， 传动比扭曲、雄性不育和胚胎致死。 这将通过选择性克隆t片段来实现，检查 候选基因的转录图谱，并识别候选基因 一种有基因排列的野生鼠种--斯普雷特斯的基因 在Chr 17上，它类似于t复合体的一部分。第三个目标是 定义t复合体中负责 小鼠明确的交配行为和攻击性 很复杂。这将通过分子组合来实现 半自然小鼠种群分析，定位重组 同源基因实验小鼠的断裂点，以及区域的分离- 从同源小鼠文库中克隆的特定片段。全部三个目标 是相互关联的，因为追求它们将有助于建立一种凝聚力 Chr 17基因中特定突变如何积累的模型 帮助形成了一个在过去的几年里自我繁殖的基因组区域 200万年来全世界超过25%的野鼠 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.