This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What is Gene Ontology?
Gene ontology is the field of biological research that is attempting to unify all biological information known about specific genes and how they act in various species. The need for this was recognized when genomic sequencing became more accessible and uncovered that many genes act similarly throughout all eukaryotes. Thus, the idea was that compiling all of the genetic and genomic information known in all model organisms, we may be able to generalize findings to other organisms and further research more quickly and cost-effectively. [1] Most of the existing information regarding gene ontology is compiled into the Gene Ontology Resource (GO)
Three characteristics are investigated by gene ontology:
Biological Process: This is the molecular events the gene or protein contributes to. These events are defined specifically as having "a defined beginning and end" by the Gene Ontology Consortium. [2]
Molecular Function: This refers to the activities the protein carries out at a molecular level. This term refers specifically to the action itself not to the other molecules involved or to the context in which the action occurs. [2]
Cellular Component: This is the area, construct, or organelle in which the gene acts. [2]
Three characteristics are investigated by gene ontology:
Biological Process: This is the molecular events the gene or protein contributes to. These events are defined specifically as having "a defined beginning and end" by the Gene Ontology Consortium. [2]
Molecular Function: This refers to the activities the protein carries out at a molecular level. This term refers specifically to the action itself not to the other molecules involved or to the context in which the action occurs. [2]
Cellular Component: This is the area, construct, or organelle in which the gene acts. [2]
What is the Gene Ontology of MTHFR?
Molecular Process
MTHFR catalyzes the reduction of 5,10 methylene-THF into 5-methyl-THF. The term reduction indicates a gaining of electrons. In this reaction, four electrons are gained in the form of four hydrogens (circled in pink). This molecular process is facilitated by energy released from the oxidation of the biological cofactor NADPH. [4] |
Discussion
Overall, the gene ontology of mthfr indicates it is involved primarily with metabolic processes within the cell. More specifically, it catalyzes reduction reactions to facilitate the production of cellular methionine. The cellular component of MTHFR indicates it only acts at the plasma membrane. This is likely due to the mechanism of homocysteine methylation. Homocysteine is toxic, and if no more methionine is needed, homocysteine is transported outside the cell immediately and degraded. [6] Thus, remethylation must occur near the membrane.
The biological contribution of homocysteine may be part of the underlying mechanism by which spina bifida develops. Research has demonstrated that homocysteine levels are elevated in people homozygous for a mutation on MTHFR. [7] Thus, the toxicity of elevated homocysteine may contribute to the failure of the neural tube to close.
The biological contribution of homocysteine may be part of the underlying mechanism by which spina bifida develops. Research has demonstrated that homocysteine levels are elevated in people homozygous for a mutation on MTHFR. [7] Thus, the toxicity of elevated homocysteine may contribute to the failure of the neural tube to close.
References:
[1] Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Davis, A.P., Dolinski, K., Dwight, S.S., Eppig, J.T., Harris, M.A., Hill, D.P., Issel-Tarver, L., Kasarskis, A., Lewis, S., Matese, J.C., Richardson, J.E., Ringwald, M., Rubin, G.M. & Sherlock, G. (2011). Gene ontology: Tool for unification of biology. Nature Genetics, 25, 25-29.
[2] Gene Ontology Consortium. (n.d.) An Introduction to Gene Ontology. Retrieved from: ftp://ftp.geneontology.org/go/www/GO.doc.shtml
[3] Mandaviya, P.R., Stolk, L. & Heil, S.G. 2014. Homocysteine and DNA methylation: A review of animal and human literature. Elsevier, 113, 243-252.
[4] NIH. (n.d.) MTHFR Gene. Genetics Home Reference. Retrieved from: https://ghr.nlm.nih.gov/gene/MTHFR
[5] https://www.proteinatlas.org/
[6] Blom, H.J & Smulders, Y. (2011). Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. Journal of Inherited Metabolic Diseases, 34, 75-81.
[7] Castro, R., Rivera, I., Ravasco, P., Camilo, M.E., Jakobs, C., Blom, H.J. & de Almeida, I.T. 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T and 1298A→C mutations are associated with DNA hypomethylation. Journal of Medical Genetics.
Images:
Header: https://www.frontiersin.org/journals/genetics
Image 1: https://jmg.bmj.com/content/41/6/454
Image 2: https://commons.wikimedia.org/wiki/File:MTHFR_reaction.svg
Image 3: https://www.proteinatlas.org/ENSG00000177000-MTHFR/cell
[1] Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Davis, A.P., Dolinski, K., Dwight, S.S., Eppig, J.T., Harris, M.A., Hill, D.P., Issel-Tarver, L., Kasarskis, A., Lewis, S., Matese, J.C., Richardson, J.E., Ringwald, M., Rubin, G.M. & Sherlock, G. (2011). Gene ontology: Tool for unification of biology. Nature Genetics, 25, 25-29.
[2] Gene Ontology Consortium. (n.d.) An Introduction to Gene Ontology. Retrieved from: ftp://ftp.geneontology.org/go/www/GO.doc.shtml
[3] Mandaviya, P.R., Stolk, L. & Heil, S.G. 2014. Homocysteine and DNA methylation: A review of animal and human literature. Elsevier, 113, 243-252.
[4] NIH. (n.d.) MTHFR Gene. Genetics Home Reference. Retrieved from: https://ghr.nlm.nih.gov/gene/MTHFR
[5] https://www.proteinatlas.org/
[6] Blom, H.J & Smulders, Y. (2011). Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. Journal of Inherited Metabolic Diseases, 34, 75-81.
[7] Castro, R., Rivera, I., Ravasco, P., Camilo, M.E., Jakobs, C., Blom, H.J. & de Almeida, I.T. 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T and 1298A→C mutations are associated with DNA hypomethylation. Journal of Medical Genetics.
Images:
Header: https://www.frontiersin.org/journals/genetics
Image 1: https://jmg.bmj.com/content/41/6/454
Image 2: https://commons.wikimedia.org/wiki/File:MTHFR_reaction.svg
Image 3: https://www.proteinatlas.org/ENSG00000177000-MTHFR/cell