Dynamic evolution of the mTHF gene family associated with primary metabolism across life

• Published in: BMC genomics Vol. 25; no. 1; p. 432
• Main Authors: Rork, Adam M, Bala, Arthi S, Renner, Tanya
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01-05-2024; BioMed Central; BMC
• Subjects: Amino acids; Archaea; Archaea - genetics; Archaea - metabolism; Bacteria; Biosynthesis; Carbon cycle; Dehydrogenases; Enzymes; Eukarya; Eukaryota - genetics; Eukaryota - metabolism; Eukaryotes; Evolution; Evolution, Molecular; Folate cycle; Folic acid; Gene family; Gene fusion; Gene mutations; Gene transfer; Gene Transfer, Horizontal; Genes; Genetic aspects; Genetic research; Genomes; Horizontal transfer; Invertebrates; Lactose; Metabolic Networks and Pathways - genetics; Metabolic pathways; Metabolism; Metabolites; Methylenetetrahydrofolate dehydrogenase; Methylenetetrahydrofolate Dehydrogenase (NADP) - genetics; Methylenetetrahydrofolate Dehydrogenase (NADP) - metabolism; Multigene Family; Nucleotides; Phylogeny; Proteins; Self defense; Vertebrates; Vitamin B; United States; Eukarya; Archaea; Bacteria; Evolution; One-carbon metabolism; Gene family; Folate cycle
• ISSN: 1471-2164; 1471-2164
• 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.