Neural tube defects (NTDs) are common malformities resulting in exposed spinal cord or brain tissues caused by the inability to close the neural tube in embryogenesis. Previous research has shown folate deficiency increases the risk of NTDs. A folic acid metabolism gene, serine hydroxymethyltransferase (SHMT) is responsible for the synthesis of thymidylates, purines, and methionine which are important for DNA replication especially during embryogenesis. Typically, eukaryotes have two copies of SHMT which are either localized to remain in the cytosol or transferred to the mitochondria. The different localizations are a result of mitochondrial target sequences on the N-terminus. Interestingly, the model system Caenorhabditis elegans only have one homolog of SHMT called mel-32 and it was unclear if this gene’s product was cytosolic, mitochondrial, or both. To address this question, a bioinformatics approach was taken to identify if mel-32/SHMT has a mitochondrial transfer sequence. We identified putative mitochondrial transfer sequences that are present in specific isoforms. Molecular phylogenies of different organisms were then generated to show prominent cytosolic SHMT and mitochondrial SHMT clustering especially around the phyla Nematoda, Arthropoda, and Tardigrada. By comparing isoforms with different SHMT localizations, potential mitochondrial target sequences were identified for organisms that could later be experimentally assessed.
Hally, A. (2021). Identification of mitochondrial transfer sequences in homologs of a folic acid metabolism gene. Retrieved from https://digitalcommons.wcupa.edu/bio_stuwork/13