Molecular evolution of the vertebrate TLR1 gene family--a complex history of gene duplication, gene conversion, positive selection and co-evolution.

Molecular evolution of the vertebrate TLR1 gene family--a complex history of gene duplication, gene conversion, positive selection and co-evolution.
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DOI:
10.1186/1471-2148-11-149
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发表时间:
2011-05-28
影响因子:
3.4
通讯作者:
Burt DW
Burt DW
中科院分区:
生物学2区
文献类型:
--
作者:
Huang Y;Temperley ND;Ren L;Smith J;Li N;Burt DW

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Toll样受体代表了I型跨膜糖蛋白的一个大的超家族,一些常见于广泛的物种,而另一些在它们的分布上更受限制。Toll样受体超家族的大多数成员几乎没有旁系同源物;例外的是TLR 1基因家族,其在哺乳动物中具有四个密切相关的基因TLR 1、TLR 2、TLR 6和TLR 10,在鸟类中具有四个密切相关的基因TLR 1A、TLR 1B、TLR 2A和TLR 2B。这些基因以前被认为是由一系列独立的基因复制产生的。为了进一步了解TLR 1基因家族在脊椎动物中的进化模式,我们克隆了鸭和火鸡的TLR 1A、TLR 1B、TLR 2A和TLR 2B基因序列,构建了系统发育树,预测了正向选择下的密码子,并利用4种鸟类、28种哺乳动物、1种两栖动物和1种鱼类的序列鉴定了TLR 1基因家族中的共进化氨基酸对。这种详细的系统发育分析不仅阐明了鸟类和哺乳动物TLR 1基因家族内的基因获得和丢失,而且还定义了这些脊椎动物之间的直系同源物。在哺乳动物中,我们预测了TLR 1、TLR 2和TLR 6中正选择下的氨基酸位点,但不预测TLR 10。我们检测TLR 2中的氨基酸残基和该基因家族的其他成员之间的共同进化,预测保持其形成功能性异源二聚体的能力。在鸟类中,我们预测TLR 2A和TLR 2B基因在功能上重要的氨基酸残基的正选择。我们表明,TLR 1基因家族大多受到纯化选择,但也响应定向选择在几个网站,可能是为了应对病原体的挑战。我们对脊椎动物TLR 1家族的系统发育和结构分析阐明了它们的进化起源,并预测了可能在宿主防御入侵病原体中重要的氨基酸残基。
The Toll-like receptors represent a large superfamily of type I transmembrane glycoproteins, some common to a wide range of species and others are more restricted in their distribution. Most members of the Toll-like receptor superfamily have few paralogues; the exception is the TLR1 gene family with four closely related genes in mammals TLR1, TLR2, TLR6 and TLR10, and four in birds TLR1A, TLR1B, TLR2A and TLR2B. These genes were previously thought to have arisen by a series of independent gene duplications. To understand the evolutionary pattern of the TLR1 gene family in vertebrates further, we cloned the sequences of TLR1A, TLR1B, TLR2A and TLR2B in duck and turkey, constructed phylogenetic trees, predicted codons under positive selection and identified co-evolutionary amino acid pairs within the TLR1 gene family using sequences from 4 birds, 28 mammals, an amphibian and a fish. This detailed phylogenetic analysis not only clarifies the gene gains and losses within the TLR1 gene family of birds and mammals, but also defines orthologues between these vertebrates. In mammals, we predict amino acid sites under positive selection in TLR1, TLR2 and TLR6 but not TLR10. We detect co-evolution between amino acid residues in TLR2 and the other members of this gene family predicted to maintain their ability to form functional heterodimers. In birds, we predict positive selection in the TLR2A and TLR2B genes at functionally significant amino acid residues. We demonstrate that the TLR1 gene family has mostly been subject to purifying selection but has also responded to directional selection at a few sites, possibly in response to pathogen challenge. Our phylogenetic and structural analyses of the vertebrate TLR1 family have clarified their evolutionary origins and predict amino acid residues likely to be important in the host's defense against invading pathogens.
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