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 <i>Shmt</i> genes and analyze the expression patterns of <i>Shmt</i> genes in developing amphioxus (<i>Branchiostoma lanceolatum</i>). Phylogenetic analyses indicate the presence of <i>Shmt1</i> and <i>Shmt2</i> orthologs in deuterostomes, spiralians and placozoans, which is consistent with an ancient <i>Shmt</i> gene duplication event predating bilaterian diversification. Gene expression analyses in developing amphioxus show that <i>Shmt2</i> expression is confined to the somites and absent from neural tissues. In contrast, <i>Shmt1</i> is broadly expressed across germ layers, but its transcription is restricted to tissues characterized by strong cell proliferation. Notably, <i>Shmt1</i> 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 <i>Shmt1</i> 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.