AUTHOR=Davoodi Peymaneh , Ghaderi-Zefrehei Mostafa , Dolatabady Mustafa Muhaghegh , Razmkabir Mohammad , Kianpour Somayeh , Esfahani Effat Nasre , Smith Jacqueline TITLE=In silico investigation of uncoupling protein function in avian genomes JOURNAL=Frontiers in Veterinary Science VOLUME=Volume 9 - 2022 YEAR=2023 URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2022.1085112 DOI=10.3389/fvets.2022.1085112 ISSN=2297-1769 ABSTRACT=This study aimed to perform a set of in-silico investigations primarily focused on the structural, biological, and biomimetic functions of uncoupling protein (avUCP). Thereby, using in silico genome analyses among 8 avian species (chicken, turkey, swallow, manakin, sparrow, wagtail, pigeon, and mallard) and a series of bioinformatic approaches, we provide phylogenetic inference and comparative genomics of avUCPs and investigate whether sequence variation can alter coding sequence characteristics, the protein structure, and its biological features. Complementarily, a combination of literature mining and prediction approaches was also applied to predict the gene networks of avUCP to identify genes, pathways, and biological crosstalk associated with avUCP function. The results showed the evolutionary alteration of UCP proteins in different avian species. It can also be deduced that avUCP, in migrant or domestic birds, may increase heat stress resistance by reducing fatty acid transport/b-oxidation and thermoregulation alongside antioxidant defense mechanisms. The predicted gene network for avUCP highlighted a cluster of 21 genes involved in response to stress and 28 genes related to lipid metabolism and the proton buffering system. Finally, among 11 enriched pathways, crosstalk of 5 signaling pathways including MAPK, adipocytokine, mTOR, insulin, ErbB, and GnRH was predicted, indicating a possible combination of positive or negative feedback among pathways to regulate avUCP functions. Genetic selection for fast-growing commercial poultry has unintentionally increased susceptibility to many kinds of oxidative stress, and so avUCP could be considered as a potential candidate gene for balancing energy expenditure and reactive oxygen species production, especially in breeding programs. In conclusion, avUCP can be introduced as a pleiotropic gene that requires the contribution of regulatory genes, hormones, pathways, and genetic crosstalk to allow its finely-tuned function.