In converting serine to glycine it transfers a methyl group to tetrahydrofolate and, hence, into the one carbon pool. This tetrahydrofolate pool is utilized during the biosynthesis of thymidine, lipids, and other essential molecules. A computer homology search for serine hydroxymethyltransferase homologs in C. elegans revealed one gene, C05D11.11. The cosmid C05D11 rescued five essential genes in the region, while a subclone containing CeSHMT by itself rescued the maternal effect lethal phenotype of mel-32. The C. elegans mutant mel-32 represents the only known instance where a SHMT mutant is lethal.
Mutant embryos show a delayed cell cycle, possibly consistent with a lack of thymidine.
Heteroduplex analysis of the 17 alleles with 5 overlapping PCR fragments has positioned 13 of the mutations into specific regions of the gene. Sequence analysis of the specific regions of each mutant is underway. It is hoped that the availability of these 17 alleles will help determine which of the highly conserved residues is essential to SHMT function. The intragenic complementation tests of these alleles shows a complex pattern, with some combinations surviving until early larval stages. This pattern suggests that SHMT is a multimeric protein.