Division of Genetics, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Antioxid Redox Signal. 2020 Sep 1;33(7):525-536. doi: 10.1089/ars.2020.8044. Epub 2020 Apr 23.
Bioinformatics has brought important insights into the field of selenium research. The progress made in the development of computational tools in the last two decades, coordinated with growing genome resources, provided new opportunities to study selenoproteins. The present review discusses existing tools for selenoprotein gene finding and other bioinformatic approaches to study the biology of selenium. The availability of complete selenoproteomes allowed assessing a global distribution of the use of selenocysteine (Sec) across the tree of life, as well as studying the evolution of selenoproteins and their biosynthetic pathway. Beyond gene identification and characterization, human genetic variants in selenoprotein genes were used to examine adaptations to selenium levels in diverse human populations and to estimate selective constraints against gene loss. The synthesis of selenoproteins is essential for development in mice. In humans, several mutations in selenoprotein genes have been linked to rare congenital disorders. And yet, the mechanism of Sec insertion and the regulation of selenoprotein synthesis in mammalian cells are not completely understood. Omics technologies offer new possibilities to study selenoproteins and mechanisms of Sec incorporation in cells, tissues, and organisms.
生物信息学为硒研究领域带来了重要的见解。在过去二十年中,计算工具的发展取得了进展,与不断增长的基因组资源相协调,为研究硒蛋白提供了新的机会。本综述讨论了现有的硒蛋白基因发现工具和其他生物信息学方法来研究硒的生物学。完整硒蛋白组的可用性使得能够评估硒代半胱氨酸 (Sec) 在整个生命之树上的使用分布,以及研究硒蛋白的进化及其生物合成途径。除了基因鉴定和特征描述外,硒蛋白基因中的人类遗传变异被用于研究不同人类群体中硒水平的适应性以及对基因丢失的选择限制。硒蛋白的合成对于小鼠的发育至关重要。在人类中,硒蛋白基因的几种突变与罕见的先天性疾病有关。然而,Sec 插入的机制和哺乳动物细胞中硒蛋白合成的调节还不完全清楚。组学技术为研究硒蛋白和 Sec 在细胞、组织和生物体中的掺入机制提供了新的可能性。