Identification of Potential Orthologous pmt-2 Genes in Parasitic Nematodes
Disciplines
Bioinformatics | Genetics | Genomics | Parasitology
Abstract (300 words maximum)
Nematodes such as Caenorhabditis elegans and the parasitic Haemonchus contortus share a phosphobase methylation pathway, analogous to those in plants and Plasmodium species. This pathway converts phosphoethanolamine (pEA) to phosphocholine (pCho) for the Kennedy pathway to enable the production of phosphatidylcholine- an essential component for phospholipid biosynthesis. This pathway is divided into two functional domains of phosphoethanolamine methyltransferase: N-terminal (PMT-1), which initiates the methylation of pEA to phosphomonomethylethanolamine (pMME), and C-terminal (PMT-2) that continues to methylate the pMME and the phosphodimethylethanolamine (pDME) intermediate to yield pCho. In nematodes, the PMTs are encoded by two distinct paralogous genes. There is growing interest in studying the structure and biochemical function of PMT-2 for potential drug targeting, driven by the need to develop novel nematicides that can combat parasitic nematodes that infect animal, human, and plant hosts; fueled by recent concerns about anthelmintic resistance in nematodes and the rising prevalence of parasitic infections associated with the expanding human population, changes in climate, and agricultural intensification. We employed the NIH's Basic Local Alignment Tool (BLAST) to detect probable nucleotide and protein sequences in parasites containing unannotated pmt-2 genes orthologous to those known in C. elegans and H. contortus across numerous sequence databases. Additionally, the Conserved Domain Search, also provided by the NIH, aided in locating conserved domains characteristic of PMT-2, namely the N-terminal vestigial domain and the S-adenosylmethionine-dependent methyltransferase (SAM) binding site. The presence of a pmt-2 gene was further analyzed using gene prediction software like GENSCAN and GeneID, which are capable of identifying and estimating the exons of protein-coding genes to formulate hypothetical sequences that may be identified in the genomes of parasitic nematodes in future studies. To date, we have predicted a number of pmt-2 genes, including those in Teladorsagia circumcincta, Ascaris lumbricoides, and Globodera rostochiensis, and plan to expand our predictions to other nematodes listed in the neglected tropical diseases category, as well as others of significant medical, veterinary, and agricultural importance.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Martin L. Hudson
Identification of Potential Orthologous pmt-2 Genes in Parasitic Nematodes
Nematodes such as Caenorhabditis elegans and the parasitic Haemonchus contortus share a phosphobase methylation pathway, analogous to those in plants and Plasmodium species. This pathway converts phosphoethanolamine (pEA) to phosphocholine (pCho) for the Kennedy pathway to enable the production of phosphatidylcholine- an essential component for phospholipid biosynthesis. This pathway is divided into two functional domains of phosphoethanolamine methyltransferase: N-terminal (PMT-1), which initiates the methylation of pEA to phosphomonomethylethanolamine (pMME), and C-terminal (PMT-2) that continues to methylate the pMME and the phosphodimethylethanolamine (pDME) intermediate to yield pCho. In nematodes, the PMTs are encoded by two distinct paralogous genes. There is growing interest in studying the structure and biochemical function of PMT-2 for potential drug targeting, driven by the need to develop novel nematicides that can combat parasitic nematodes that infect animal, human, and plant hosts; fueled by recent concerns about anthelmintic resistance in nematodes and the rising prevalence of parasitic infections associated with the expanding human population, changes in climate, and agricultural intensification. We employed the NIH's Basic Local Alignment Tool (BLAST) to detect probable nucleotide and protein sequences in parasites containing unannotated pmt-2 genes orthologous to those known in C. elegans and H. contortus across numerous sequence databases. Additionally, the Conserved Domain Search, also provided by the NIH, aided in locating conserved domains characteristic of PMT-2, namely the N-terminal vestigial domain and the S-adenosylmethionine-dependent methyltransferase (SAM) binding site. The presence of a pmt-2 gene was further analyzed using gene prediction software like GENSCAN and GeneID, which are capable of identifying and estimating the exons of protein-coding genes to formulate hypothetical sequences that may be identified in the genomes of parasitic nematodes in future studies. To date, we have predicted a number of pmt-2 genes, including those in Teladorsagia circumcincta, Ascaris lumbricoides, and Globodera rostochiensis, and plan to expand our predictions to other nematodes listed in the neglected tropical diseases category, as well as others of significant medical, veterinary, and agricultural importance.