Abstract
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.
Highlights
Peripheral tolerance mechanisms are an essential part of the adaptive immune system, controlling inflammation and preventing inappropriate immune responses to autoantigens, fetal alloantigens and gastrointestinal microflora [1,2]
The Forkhead box transcription factor FoxP3 plays a key role in the development and function of regulatory T cells (Tregs), which make a major contribution to peripheral tolerance [3]
BLASTP analysis against the NCBI nr database suggested that the annotation of the ground tit gene was correct, with top matches to mammalian and reptilian FoxP3; in contrast, that of the turkey gene was erroneous, with top matches to avian FoxP4
Summary
Peripheral tolerance mechanisms are an essential part of the adaptive immune system, controlling inflammation and preventing inappropriate immune responses to autoantigens, fetal alloantigens and gastrointestinal microflora [1,2]. The Forkhead box transcription factor FoxP3 plays a key role in the development and function of regulatory T cells (Tregs), which make a major contribution to peripheral tolerance [3]. FoxP3 belongs to the Fox family of transcription factors, which share an 80 to 100 amino acid DNA-binding domain known as the forkhead box [4]. The forkhead (FRK) domain is the only part of the protein sequence that can be aligned across all members of the Fox family and is a critical determinant in phylogenetic studies [5]. All four proteins share a zinc finger (ZF), leucine zipper (LZ) and PLOS ONE | DOI:10.1371/journal.pone.0150988. All four proteins share a zinc finger (ZF), leucine zipper (LZ) and PLOS ONE | DOI:10.1371/journal.pone.0150988 March 3, 2016
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