Evolutionary status of the genetic background in the wild mice and its participation in manifestation of the genes for biological functions in mouse models

(1)三个小鼠亚种群的遗传分化估计：我们已经从遗传学的角度证明了小家鼠可能分化为三个小鼠亚种群，小家鼠亚种群，栗亚种群和小家鼠亚种群，每个亚种群相互之间相隔大约100万年。对这些亚种群1000个微卫星DNA位点的基因扫描分析证实了上述可能性。8个野生株22个基因位点的核苷酸序列比较也显示出相似的聚类。在用FISH技术进行的细胞遗传学调查中，发现东北亚人群主要卫星DNA的染色体分布有5种类型。在北海道，东部种群线粒体DNA为小肌群型，中部种群为栗色群型。但是Y染色体上的Sry基因 ...更多信息 然而，在我们调查的种群中，我几乎是肌肉型的。(2)当地人群的遗传多态性：d-、p-和w1单倍型血红蛋白基因b1和b2的核苷酸序列分析表明，p单倍型是具有d单倍型b1和w1单倍型b2的重组体。内含子核苷酸序列表明，d-和w1单倍型的可能的分化发生在大约200万年前，d-和w1单倍型之间的重组发生在大约20万年前。在哈萨克族人群中发现了一种新的Hbb单倍型w2，经核苷酸序列测定，该单倍型为w1单倍型b1和d单倍型b2的重组体。在该区域，还发现了一个转移变异体。在栗属Mysole群体中发现了肽酶-3缺失突变体，并将其固定为MYS/Mz近交系。强烈提示，仅在栗亚种组中存在对乌拉坦诱导的肺肿瘤的遗传易感性的显性抑制的可能性。(3)进化上遥远的遗传背景对基因表现的影响：Rim 4突变基因在实验小鼠品系C57 BL的遗传背景中表现出明显的多指表型，而在日本野生型MSM品系中完全没有表现出多指表型。第二个调节基因在2号染色体上的Ist附近检测到。导致尾短突变的遗传元件被鉴定为核糖体蛋白Rp 138。同样在这种情况下，MSM衍生的Rp 138抑制了尾短表型。少

(1) Estimation of the genetic differentiation of three mouse subspecies groups :We have already demonstrated the possible differentiation of Mus musculus species into three mouse subspecies groups, domesticus-, castaneus- and musculus subspecies group from genetic view point, each of which was mutually separated by roughly one million years. The gene scan analysis of 1000 microsatellite DNA loci in these subspecies groups approved the above possibility. Comparison of the nucleotide sequences in 22 gene loci among 8 wild derived strains also showed the similar grouping. In cytogenetical survey using FISH technique, five types in the chromosomal distribution pattern of major satellite DNAs were observed in northeast Asian populations. These are musculus-, gansuensis-, molossinus-, musculus+molossinus- and musculus+castaneus type.In Hokkaido, mitochondoria DNA was musculus group type in the eastern populations and castaneus group type in the central populations. But Sry gene on Y chromoso … More me, however, was almost musculus type in the populations we surveyed.(2) Genetic polymorphism in local populations :The nucleotide sequence analyses of d-, p- and w1 haplotype hemoglobin genes , b1 and b2, demonstrated that p haplotype was a recombinant having d haplotype b1 and w1 haplotype b2. Intron nucleotide sequences suggested that the possible differentiation of d- and w1 haplotype occurred around 2 million years ago and the recombination between d- and w1 haplotype around 200 thousands years ago. In a Kazakstan population, a new Hbb haplotype w2 was found. The nucleotide sequence data suggested that it was a recombinant carrying w1 haplotype b1 and d haplotye b2. In this area, a transferring variant was found out as well. In a Mysole population belonging to castaneus group, peptidase-3 delition mutant was observed and fixed as MYS/Mz inbred strain. The possibility that a dominant suppression in the genetic susceptibility to urethane induced lung tumor was present only in the castaneus subspecies group, was strongly suggested.(3) Effect of evolutionarily remote genetic background on gene manifestation :Rim4 mutant gene exhibited the clear polydactylous phenotype in the genetic background of laboratory mouse strain C57BL, while it completely failed to show it in the Japanese wild derived MSM strain. The second regulatory gene was detected near Ist on the chromosome 2. Causative genetic element for Tail-short mutation was identified as Rp138, a ribosome protein. Again in this case, MSM-derived Rp138 suppressed the Tail-short phnotype. Less