Cellular and Molecular Physiology Department, Yale School of Medicine, New Haven, CT 06510, USA.
Systems Biology Institute, Yale West Campus, West Haven, CT 06516, USA.
Biomolecules. 2023 Aug 28;13(9):1314. doi: 10.3390/biom13091314.
Homology search and phylogenetic analysis have commonly been used to annotate gene function, although they are prone to error. We hypothesize that the power of homology search in functional annotation depends on the coupling of sequence variation to functional diversification, and we herein focus on the SoLute Carrier (SLC25) family of mitochondrial metabolite transporters to survey this coupling in a family-wide manner. The SLC25 family is the largest family of mitochondrial metabolite transporters in eukaryotes that translocate ligands of different chemical properties, ranging from nucleotides, amino acids, carboxylic acids and cofactors, presenting adequate experimentally validated functional diversification in ligand transport. Here, we combine phylogenetic analysis to profile SLC25 transporters across common eukaryotic model organisms, from , , , , to , and assess their sequence adaptations to the transported ligands within individual subfamilies. Using several recently studied and poorly characterized SLC25 transporters, we discuss the potentials and limitations of phylogenetic analysis in guiding functional characterization.
同源搜索和系统发育分析常用于注释基因功能，尽管它们容易出错。我们假设同源搜索在功能注释中的作用取决于序列变异与功能多样化的结合，我们在此集中研究线粒体代谢物转运蛋白的 Solute Carrier (SLC25) 家族，以全面调查这种结合。SLC25 家族是真核生物中线粒体代谢物转运蛋白中最大的家族，可转运不同化学性质的配体，从核苷酸、氨基酸、羧酸和辅因子，在配体转运方面具有足够的经过充分验证的功能多样化。在这里，我们结合系统发育分析来研究常见真核模式生物中的 SLC25 转运蛋白，从 到 ，并评估它们在单个亚家族中对转运配体的序列适应性。我们使用了几种最近研究的和特征较差的 SLC25 转运蛋白，讨论了系统发育分析在指导功能特征方面的潜力和局限性。
