The Expression of Shmt Genes in Amphioxus Suggests a Role in Tissue Proliferation Rather than in Neurotransmission

Serine hydroxymethyltransferases (SHMTs) are key enzymes in one-carbon metabolism, with vertebrates possessing two paralogs, cytosolic SHMT1 and mitochondrial SHMT2, implicated in nucleotide biosynthesis and glycine metabolism. In this study, we investigate the evolutionary history of animal Shmt genes and analyze the expression patterns of Shmt genes in developing amphioxus (Branchiostoma lanceolatum). Phylogenetic analyses indicate the presence of Shmt1 and Shmt2 orthologs in deuterostomes, spiralians and placozoans, which is consistent with an ancient Shmt gene duplication event predating bilaterian diversification. Gene expression analyses in developing amphioxus show that Shmt2 expression is confined to the somites and absent from neural tissues. In contrast, Shmt1 is broadly expressed across germ layers, but its transcription is restricted to tissues characterized by strong cell proliferation. Notably, Shmt1 expression in the nervous system does not match the distribution of glycinergic neuron populations, implying a negligible role in glycine neurotransmitter synthesis. Instead, the spatial correlation of Shmt1 expression with mitotically active domains suggests a primary function in nucleotide biosynthesis via one-carbon metabolism. These findings indicate that SHMTs predominantly support cell proliferation rather than neurotransmission in amphioxus.