Natural selection drives recurrent formation of activating killer cell immunoglobulin-like receptor and Ly49 from inhibitory homologues.
Natural selection drives recurrent formation of activating killer cell immunoglobulin-like receptor and Ly49 from inhibitory homologues.
复制标题
DOI：
10.1084/jem.20042558
复制
发表时间：
2005-04-18
期刊：
影响因子：
--
通讯作者：
Parham P
中科院分区：
文献类型：
--
作者：
Abi-Rached L;Parham P
杀伤细胞igg样受体（KIRs）的表达使人类自然杀伤细胞群和T细胞亚群多样化。虽然抑制性KIR的主要组织相容性复合体I类结合功能是已知的，但激活受体的特异性却难以分析。为了更好地了解激活KIR及其与抑制KIR的关系，我们采用了重建它们的自然历史和Ly49（啮齿动物的类似系统）的方法。一个普遍的原则是，抑制受体是祖先的，激活受体是通过突变从它们进化而来的。这种功能开关的进化过程在不同物种中独立发生，产生具有相似信号域的激活KIR和Ly49基因。选择这种趋同进化的是信号适配器，它们比任何KIR或Ly49都要古老和保守。功能转移后，通过重组和基因复制形成进一步激活受体。激活受体的寿命很短，并且反复进化，这表明它们受制于相互冲突的选择，这与激活KIR与抵抗感染、繁殖成功和对自身免疫的易感性的关联是一致的。我们的分析表明了一个两阶段的模型，在这个模型中，激活KIR或Ly49最初受到快速增加其频率的正选择的影响，然后是减少其频率并最终导致损失的负选择。
Expression of killer cell Ig-like receptors (KIRs) diversifies human natural killer cell populations and T cell subpopulations. Whereas the major histocompatibility complex class I binding functions of inhibitory KIR are known, specificities for the activating receptors have resisted analysis. To understand better activating KIR and their relationship to inhibitory KIR, we took the approach of reconstructing their natural history and that of Ly49, the analogous system in rodents. A general principle is that inhibitory receptors are ancestral, the activating receptors having evolved from them by mutation. This evolutionary process of functional switch occurs independently in different species to yield activating KIR and Ly49 genes with similar signaling domains. Selecting such convergent evolution were the signaling adaptors, which are older and more conserved than any KIR or Ly49. After functional shift, further activating receptors form through recombination and gene duplication. Activating receptors are short lived and evolved recurrently, showing they are subject to conflicting selections, consistent with activating KIR's association with resistance to infection, reproductive success, and susceptibility to autoimmunity. Our analysis suggests a two-stage model in which activating KIR or Ly49 are initially subject to positive selection that rapidly increases their frequency, followed by negative selection that decreases their frequency and leads eventually to loss.
登录
查看更多内容
影响因子：
--
作者：
Grendell, RL;Hughes, AL;Golos, TG
通讯作者：
Golos, TG
影响因子：
10.7
作者：
Adkins, RM;Gelke, EL;Honeycutt, RL
通讯作者：
Honeycutt, RL
DOI：
10.1073/pnas.90.24.12000
发表时间：
1993-12-15
影响因子：
11.1
作者：
COLONNA, M;BORSELLINO, G;STROMINGER, JL
通讯作者：
STROMINGER, JL
影响因子：
5.4
作者：
Biassoni, R;Pessino, A;Moretta, A
通讯作者：
Moretta, A
影响因子：
9.5
作者：
Kumar, S;Tamura, K;Nei, M
通讯作者：
Nei, M