Hammer M F, Bliss S, Silver L M
Department of Molecular Biology, Princeton University, New Jersey 08544.
Genetics. 1991 Aug;128(4):799-812. doi: 10.1093/genetics/128.4.799.
Mouse t haplotypes are distinguished from wild-type forms of chromosome 17 by four nonoverlapping paracentric inversions which span a genetic distance of 20 cM. These inversion polymorphisms are responsible for a 100-200-fold suppression of recombination which maintains the integrity of complete t haplotypes and has led to their divergence from the wild-type chromosomes of four species of house mice within which t haplotypes reside. As evidence for the long period of recombinational isolation, alleles that distinguish all t haplotypes from all wild-type chromosomes have been established at a number of loci spread across the 20-cM variant region. However, a more complex picture emerges upon analysis of other t-associated loci. In particular, "mosaic haplotypes" have been identified that carry a mixture of wild-type and t-specific alleles. To investigate the genetic basis for mosaic chromosomes, we conducted a comprehensive analysis of eight t complex loci within 76 animals representing 10 taxa in the genus Mus, and including 23 previously characterized t haplotypes. Higher resolution restriction mapping and sequence analysis was also performed for alleles at the Hba-ps4 locus. The results indicate that a short tract of DNA was transferred relatively recently across an inversion from a t haplotype allele of Hba-ps4 to the corresponding locus on a wild-type homolog leading to the creation of a new hybrid allele. Several classes of wild-type Hba-ps4 alleles, including the most common form in inbred strains, appear to be derived from this hybrid allele. The accumulated data suggest that a common form of genetic exchange across one of the four t-associated inversions is gene conversion at isolated loci that do not play a role in the transmission ratio distortion phenotype required for t haplotype propagation. The implications of the results pose questions concerning the evolutionary stability of gene complexes within large paracentric inversions and suggest that recombinational isolation may be best established for loci residing within a short distance from inversion breakpoints.
小鼠t单倍型与17号染色体的野生型形式的区别在于四个不重叠的臂内倒位，这些倒位跨越20厘摩的遗传距离。这些倒位多态性导致重组被抑制100 - 200倍，从而维持了完整t单倍型的完整性，并导致其与t单倍型所在的四种家鼠的野生型染色体产生分化。作为长期重组隔离的证据，在跨越20厘摩变异区域的多个位点上，已确定了区分所有t单倍型与所有野生型染色体的等位基因。然而，对其他与t相关的位点进行分析时，出现了更为复杂的情况。特别是，已鉴定出携带野生型和t特异性等位基因混合物的“镶嵌单倍型”。为了研究镶嵌染色体的遗传基础，我们对代表小家鼠属10个分类单元的76只动物中的8个t复合位点进行了全面分析，其中包括23个先前已鉴定的t单倍型。还对Hba - ps4位点的等位基因进行了更高分辨率的限制性图谱分析和序列分析。结果表明，一小段DNA相对较近期地通过倒位从Hba - ps4的t单倍型等位基因转移到野生型同源染色体上的相应位点，从而产生了一个新的杂交等位基因。包括近交系中最常见形式在内的几类野生型Hba - ps4等位基因似乎都源自这个杂交等位基因。积累的数据表明，四种与t相关的倒位之一中常见的遗传交换形式是在孤立位点上的基因转换，这些位点在t单倍型传播所需的传递比例畸变表型中不起作用。这些结果的影响引发了关于大臂内倒位内基因复合体进化稳定性的问题，并表明对于距离倒位断点较近的位点，重组隔离可能最容易建立。
