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)小鼠三个亚种群遗传分化的估计：我们已经从遗传学的角度论证了小鼠肌肉种可能分化为三个亚种群，即家鼠亚种群、卡氏小鼠亚种群和肌肉亚种群，每个亚种群之间的距离约为100万年。对这些亚种群的1000个微卫星DNA基因座的基因扫描分析证实了上述可能性。8个野生来源菌株的22个基因座的核苷酸序列比较也显示出相似的类群。在应用FISH技术进行细胞遗传学调查时，观察到东北亚人群中主要卫星DNA的5种染色体分布类型。在北海道，东部种群的线粒体DNA为肌群类型，中部种群为蓖麻群类型。但Y染色体…上的Sry基因(2)地方群体遗传多态性：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。内含子核苷酸序列表明，d-和w1单倍型的分化可能发生在大约200万年前，d-和w1单倍型之间的重组可能发生在大约20万年前。在哈萨克族人群中，发现了一种新的Hbb单倍型w2。核苷酸序列分析表明，该重组株携带W1单倍型b1和d单倍型b2。在这一地区，还发现了一个转移变种。在一个属于卡萨尼乌斯群的Mysole群中，观察到了肽酶-3缺失突变，并将其固定为MYS/Mz近交系。(3)进化上较远的遗传背景对基因表现的影响：Rim4突变基因在实验室小鼠品系C57BL的遗传背景中表现出明显的多指型表型，而在日本野生型MSM品系中完全没有表现出这种表型。在2号染色体的Ist附近检测到第二个调控基因。导致尾巴短突变的遗传因素被鉴定为核糖体蛋白Rp138。同样，在这种情况下，来自MSM的Rp138抑制了尾部短的phnotype。较少

(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