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Background  The forkhead transcription factor gene E1 (FOXE1) plays an important role in regulation of thyroid development, palate formation and hair morphogenesis in mammals. However, avian  FOXE1  genes have not been characterized and as such, codon evolution of FOXE1 orthologs in a broader evolutionary context of mammals and birds is not known.    Results  In this study we identified the avian  FOXE1  gene in chicken, turkey and zebra finch, all of which consist of a single exon. Chicken and zebra finch  FOXE1  are uniquely located on the sex-determining Z chromosome. In situ hybridization shows that chicken  FOXE1  is specifically expressed in the developing thyroid. Its expression is initiated at the placode stage and is maintained during the stages of vesicle formation and follicle primordia. Based on this expression pattern, we propose that avian  FOXE1  may be involved in regulating the evagination and morphogenesis of thyroid. Chicken  FOXE1  is also expressed in growing feathers. Sequence analysis identified two microdeletions in the avian  FOXE1  genes, corresponding to the loss of a transferable repression domain and an engrailed homology motif 1 (Eh1) C-terminal to the forkhead domain. The avian  FOXE1  proteins exhibit a significant sequence divergence of the C-terminus compared to those of amphibian and mammalian  FOXE1 . The codon evolution analysis (dN/dS) of  FOXE1  shows a significantly increased dN/dS ratio in the avian lineages, consistent with either a relaxed purifying selection or positive selection on a few residues in avian FOXE1 evolution. Further site specific analysis indicates that while relaxed purifying selection is likely to be a predominant cause of accelerated evolution at the 3'-region of avian FOXE1, a few residues might have evolved under positive selection.    Conclusions  We have identified three avian  FOXE1  genes based on synteny and sequence similarity as well as characterized the expression pattern of the chicken  FOXE1  gene during development. Our evolutionary analyses suggest that while a relaxed purifying selection is likely to be the dominant force driving accelerated evolution of avian  FOXE1  genes, a few residues may have evolved adaptively. This study provides a basis for future genetic and comparative biochemical studies of FOXE1.

Accelerated evolution of 3'avian FOXE1 genes, and thyroid and feather specific expression of chicken FoxE1