The origin of MHC class II gene polymorphism within the genus Mus
The origin of MHC class II gene polymorphism within the genus Mus
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鼠属MHC II类基因多态性的起源
作者：
T. McConnell;W. S. Talbot;R. McIndoe;E. Wakeland
小鼠(H2)主要组织相容性复合体(MHC)的I区包含一组紧密相连的高度多态基因(II类MHC基因)，这些基因控制着免疫应答。关于这种多态的起源，人们认为这种多态对于第二类蛋白在疾病免疫反应中的功能是必不可少的，这引发了两个假说。首先，高突变机制(基因转换或片段交换)促进了MHC基因多样性的快速产生。另一种选择是，在漫长的进化过程中，突变的稳定积累产生了多态，而多个特定的等位基因在物种形成(跨物种进化)中幸存下来。我们通过对IAβ等位基因的分子遗传分析，寻找了MUS属II类基因存在“片段交换”和/或“跨物种进化”的证据。结果表明，90%(28/31)的等位基因可根据限制性内切酶切点的多态和有无短分布的核苷酸单元(正弦)被组织成两个进化群。使用这个正弦序列作为进化标签，我们证明了这两个进化群中的IAβ等位基因至少在300万年前分化，并在导致几个现代Mus物种的物种形成事件中幸存下来。对代表三个进化群的八个家鼠IAβ等位基因的核苷酸序列比较表明，外显子序列的大部分差异是由于突变的稳定积累，这些突变在不同的等位基因中保持独立。但来自不同进化群体的等位基因之间的节段性交换也在β1外显子的多样化中发挥了作用。
The I region of the major histocompatibility complex (MHC) of the mouse (H2) contains a tightly-linked cluster of highly poly-morphic genes (class II MHC genes) which control immune responsiveness. Speculation on the origin of this polymorphism, which is believed to be essential for the function of the class II proteins in immune responses to disease, has given rise to two hypotheses. The first is that hypermutational mechanisms (gene conversion or segmental exchange) promote the rapid generation of diversity in MHC genes. The alternative is that polymorphism has arisen from the steady accumulation of mutations over long evolutionary peri-ods, and multiple specific alleles have survived speciation (trans-species evolution). We have looked for evidence of 'segmental exchange' and/or 'trans-species evolution' in the class II genes of the genus Mus by molecular genetic analysis of IAβ alleles. The results indicate that >90% (28 out of 31) of the alleles examined can be organized into two evolutionary groups both on the basis of restriction site polymorphisms and by the presence or absence of a short interspersed nucleotide element (SINE). Using this SINE sequence as an evolutionary tag, we demonstrate that IAβ alleles in these two evolutionary groups diverged at least three million years ago and have survived the speciation events leading to several modern Mus species. Nucleotide sequence comparisons of eight Mus m. domesticus IAβ alleles representing all three evolutionary groups indicate that most of the divergence in exon sequences is due to the steady accumulation of mutations that are maintained independently in the different alleles. But segmental exchanges between alleles from different evolutionary groups have also played a role in the diversification of β1, exons.
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表达 I-Ak 和 I-Ap 微小结构变异的小鼠中 II 类基因序列的限制性片段长度多态性。
DOI：
--
发表时间：
1986
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
McConnell,TJ;Darby,B;Wakeland,EK
通讯作者：
Wakeland,EK
野生小鼠II类组织相容性基因的重组和突变。
DOI：
--
发表时间：
1983
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Wakeland,EK;Darby,BR
通讯作者：
Darby,BR
DOI：
10.1073/pnas.84.8.2435
发表时间：
1987-04-01
影响因子：
11.1
作者：
ACHAORBEA, H;MCDEVITT, HO
通讯作者：
MCDEVITT, HO
小鼠线粒体 DNA 进化。
影响因子：
3.3
作者：
Ferris,SD;Sage,RD;Prager,EM;Ritte,U;Wilson,AC
通讯作者：
Wilson,AC