Gene conversion limits divergence of mammalian TLR1 and TLR6.
Gene conversion limits divergence of mammalian TLR1 and TLR6.
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基因转化限制了哺乳动物TLR1和TLR6的差异。
DOI：
10.1186/1471-2148-7-148
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发表时间：
2007-08-29
影响因子：
3.4
通讯作者：
Fish RJ
中科院分区：
文献类型：
--
作者：
Kruithof EK;Satta N;Liu JW;Dunoyer-Geindre S;Fish RJ
Toll 样受体 (TLR) 识别病原体相关分子模式，是先天免疫系统的重要介质。 TLR1 和 TLR6 是旁系同源物，在哺乳动物中串联位于同一染色体上。它们与 TLR2 形成异二聚体，并结合革兰氏阳性和革兰氏阴性细菌细胞壁的脂肽成分。为了鉴定 TLR1 和 TLR6 中可能对其功能很重要的保守序列，我们比较了九种哺乳动物（智人、黑猩猩、猕猴、小家鼠、褐家鼠、刺猬、牛、野猪和家犬）的蛋白质序列。直系同源蛋白的N端序列比相应的旁系同源序列表现出更大的相似性。然而，我们在 TLR1 和 TLR6 的 C 末端鉴定了一个 300 个氨基酸的区域，其中旁系同源物比直系同源物具有更大程度的序列同一性。在所研究的所有九个哺乳动物物种中观察到该区域中旁系同源物的DNA序列同一性的保留，这是由于独立的基因转换事件。每个物种中经历基因转化的区域几乎相同，编码富含亮氨酸的重复基序 16 至 19、C 末端帽基序、跨膜结构域和大部分细胞内 Toll/白细胞介素-1 受体 (TIR) 结构域。我们的结果表明，对于特定的保守区域，TLR1 和 TLR6 的分歧受到基因转换的限制，很可能是因为需要与多个细胞内和细胞外结合伙伴共同进化。因此，基因转换提供了一种限制蛋白质旁系同源物功能区域差异的机制，同时允许其他结构域进化出多样化的功能。
Toll-like receptors (TLR) recognize pathogen-associated molecular patterns and are important mediators of the innate immune system. TLR1 and TLR6 are paralogs and located in tandem on the same chromosome in mammals. They form heterodimers with TLR2 and bind lipopeptide components of gram-positive and gram-negative bacterial cell walls. To identify conserved stretches in TLR1 and TLR6, that may be important for their function, we compared their protein sequences in nine mammalian species(Homo sapiens, Pan troglodytes, Macaca mulatta, Mus musculus, Rattus norvegicus; Erinaceus europaeus, Bos Taurus, Sus scrofa and Canis familiaris). The N-terminal sequences of the orthologous proteins showed greater similarity than corresponding paralog sequences. However, we identified a region of 300 amino acids towards the C-terminus of TLR1 and TLR6, where paralogs had a greater degree of sequence identity than orthologs. Preservation of DNA sequence identity of paralogs in this region was observed in all nine mammalian species investigated, and is due to independent gene conversion events. The regions having undergone gene conversion in each species are almost identical and encode the leucine-rich repeat motifs 16 to 19, the C-terminal cap motif, the transmembrane domain and most of the intracellular Toll/interleukin-1 receptor (TIR) domain. Our results show that, for a specific conserved region, divergence of TLR1 and TLR6 is limited by gene conversion, most likely because of the need for co-evolution with multiple intracellular and extracellular binding partners. Thus, gene conversion provides a mechanism for limiting the divergence of functional regions of protein paralogs, while allowing other domains to evolve diversified functions.
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影响因子：
64.8
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