Denyer Michael P, Pinheiro Dammy Y, Garden Oliver A, Shepherd Adrian J
Department of Clinical Sciences and Services, The Royal Veterinary College, London, United Kingdom.
Institute of Structural and Molecular Biology and Department of Biological Sciences, Birkbeck, University of London, London, United Kingdom.
PLoS One. 2016 Mar 3;11(3):e0150988. doi: 10.1371/journal.pone.0150988. eCollection 2016.
The Forkhead box transcription factor FoxP3 is pivotal to the development and function of regulatory T cells (Tregs), which make a major contribution to peripheral tolerance. FoxP3 is believed to perform a regulatory role in all the vertebrate species in which it has been detected. The prevailing view is that FoxP3 is absent in birds and that avian Tregs rely on alternative developmental and suppressive pathways. Prompted by the automated annotation of foxp3 in the ground tit (Parus humilis) genome, we have questioned this assumption. Our analysis of all available avian genomes has revealed that the foxp3 locus is missing, incomplete or of poor quality in the relevant genomic assemblies for nearly all avian species. Nevertheless, in two species, the peregrine falcon (Falco peregrinus) and the saker falcon (F. cherrug), there is compelling evidence for the existence of exons showing synteny with foxp3 in the ground tit. A broader phylogenomic analysis has shown that FoxP3 sequences from these three species are similar to crocodilian sequences, the closest living relatives of birds. In both birds and crocodilians, we have also identified a highly proline-enriched region at the N terminus of FoxP3, a region previously identified only in mammals.
叉头框转录因子FoxP3对调节性T细胞（Tregs）的发育和功能至关重要，而调节性T细胞对外周耐受起主要作用。据信，FoxP3在所有已检测到的脊椎动物物种中都发挥调节作用。目前普遍的观点是鸟类中不存在FoxP3，鸟类调节性T细胞依赖于其他发育和抑制途径。受地山雀（Parus humilis）基因组中foxp3自动注释的启发，我们对这一假设提出了质疑。我们对所有可用鸟类基因组的分析表明，几乎所有鸟类物种的相关基因组组装中，foxp3基因座缺失、不完整或质量较差。然而，在游隼（Falco peregrinus）和矛隼（F. cherrug）这两个物种中，有令人信服的证据表明存在与地山雀foxp3显示同线性的外显子。更广泛的系统基因组分析表明，这三个物种的FoxP3序列与鳄鱼序列相似，鳄鱼是鸟类现存的亲缘关系最近的物种。在鸟类和鳄鱼中，我们还在FoxP3的N端鉴定出一个高度富含脯氨酸的区域，该区域以前仅在哺乳动物中发现。
