Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania, 16802, USA.
Department of Entomology, Purdue University, West Lafayette, Indiana, 47907, USA.
BMC Genomics. 2024 May 1;25(1):432. doi: 10.1186/s12864-024-10159-8.
The folate cycle of one-carbon (C1) metabolism, which plays a central role in the biosynthesis of nucleotides and amino acids, demonstrates the significance of metabolic adaptation. We investigated the evolutionary history of the methylenetetrahydrofolate dehydrogenase (mTHF) gene family, one of the main drivers of the folate cycle, across life.
Through comparative genomic and phylogenetic analyses, we found that several lineages of Archaea lacked domains vital for folate cycle function such as the mTHF catalytic and NAD(P)-binding domains of FolD. Within eukaryotes, the mTHF gene family diversified rapidly. For example, several duplications have been observed in lineages including the Amoebozoa, Opisthokonta, and Viridiplantae. In a common ancestor of Opisthokonta, FolD and FTHFS underwent fusion giving rise to the gene MTHFD1, possessing the domains of both genes.
Our evolutionary reconstruction of the mTHF gene family associated with a primary metabolic pathway reveals dynamic evolution, including gene birth-and-death, gene fusion, and potential horizontal gene transfer events and/or amino acid convergence.
一碳（C1）代谢的叶酸循环在核苷酸和氨基酸的生物合成中起着核心作用，显示出代谢适应的重要性。我们研究了叶酸循环的主要驱动因素之一——亚甲基四氢叶酸脱氢酶（mTHF）基因家族在整个生命过程中的进化历史。
通过比较基因组学和系统发育分析，我们发现古菌的几个谱系缺乏与叶酸循环功能相关的关键结构域，如 FolD 的 mTHF 催化和 NAD(P)-结合结构域。在真核生物中，mTHF 基因家族迅速多样化。例如，在变形虫、后生动物和绿藻等谱系中观察到了几个基因重复。在后生动物的一个共同祖先中，FolD 和 FTHFS 发生融合，产生了同时具有这两个基因结构域的 MTHFD1 基因。
我们对与主要代谢途径相关的 mTHF 基因家族的进化重建揭示了动态进化，包括基因的诞生和消亡、基因融合以及潜在的水平基因转移事件和/或氨基酸趋同。
