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

<p>Abstract</p> <p>Background</p> <p>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 <it>FOXE1 </it>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.</p> <p>Results</p> <p>In this study we identified the avian <it>FOXE1 </it>gene in chicken, turkey and zebra finch, all of which consist of a single exon. Chicken and zebra finch <it>FOXE1 </it>are uniquely located on the sex-determining Z chromosome. In situ hybridization shows that chicken <it>FOXE1 </it>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 <it>FOXE1 </it>may be involved in regulating the evagination and morphogenesis of thyroid. Chicken <it>FOXE1 </it>is also expressed in growing feathers. Sequence analysis identified two microdeletions in the avian <it>FOXE1 </it>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 <it>FOXE1 </it>proteins exhibit a significant sequence divergence of the C-terminus compared to those of amphibian and mammalian <it>FOXE1</it>. The codon evolution analysis (dN/dS) of <it>FOXE1 </it>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.</p> <p>Conclusions</p> <p>We have identified three avian <it>FOXE1 </it>genes based on synteny and sequence similarity as well as characterized the expression pattern of the chicken <it>FOXE1 </it>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 <it>FOXE1 </it>genes, a few residues may have evolved adaptively. This study provides a basis for future genetic and comparative biochemical studies of FOXE1.</p