Monoamine oxidase A (MAOA) by Anthony Koh-Bell and Zane Latif
Introduction
Monoamine oxidase A, abbreviated MAOA, is a gene that codes for the MAO-A protein. The protein deaminates (a verb meaning to breakdown of amino acids when there is an excess of proteins) norepinephrine, epinephrine, serotonin, and dopamine. This gene, first extensively studied in 1977, has a wide range of neurological effects with stark differences across genders. This page will explore the gene itself and its corresponding effects.
Monoamine oxidase A, abbreviated MAOA, is a gene that codes for the MAO-A protein. The protein deaminates (a verb meaning to breakdown of amino acids when there is an excess of proteins) norepinephrine, epinephrine, serotonin, and dopamine. This gene, first extensively studied in 1977, has a wide range of neurological effects with stark differences across genders. This page will explore the gene itself and its corresponding effects.
Genetic Information
The MAOA gene is part of the monoamine oxidase family. The protein that it encodes for, MAO-A, breaks down the amine neurotransmitters mentioned above (norepinephrine, serotonin, dopamine). In the majority of cells in the body, monoamine oxidase A is located on the outer membrane of mitochondria, and thus the gene encodes for mitochondrial enzymes. There are only two types of monoamine oxidases that exist within the human body, monoamine oxidase A and monoamine oxidase B. The genes that encode for both of the respective proteins are found in adjacent positions on opposite strands of the X-chromosome. Monoamine oxidase B primarily deaminates dopamine and other chemicals in the body that are less related to treatable human conditions than the chemicals regulated by monoamine oxidase A. The monoamine oxidase A gene is found at the short arm of the X-chromosome in position 11.3. It ranges from base pair 43,654,906 to base pair 43,746,823.
The MAOA gene is part of the monoamine oxidase family. The protein that it encodes for, MAO-A, breaks down the amine neurotransmitters mentioned above (norepinephrine, serotonin, dopamine). In the majority of cells in the body, monoamine oxidase A is located on the outer membrane of mitochondria, and thus the gene encodes for mitochondrial enzymes. There are only two types of monoamine oxidases that exist within the human body, monoamine oxidase A and monoamine oxidase B. The genes that encode for both of the respective proteins are found in adjacent positions on opposite strands of the X-chromosome. Monoamine oxidase B primarily deaminates dopamine and other chemicals in the body that are less related to treatable human conditions than the chemicals regulated by monoamine oxidase A. The monoamine oxidase A gene is found at the short arm of the X-chromosome in position 11.3. It ranges from base pair 43,654,906 to base pair 43,746,823.
The two images above show the location of MAOA on the X-chromosome. The image on the right is more precise, displaying the base pairs and other genes around monoamine oxidase A.
More Genetic Info (MAO-A protein)
The protein (shown below) that monoamine oxidase A encodes for, MAO-A, is a monomer with only one chain (A). There are however four structures of this protein, and two for each type of crystal structure (harmine and clorgyline). The structure below is in crystal form with harmine, a monoamine oxidase inhibitor that only affects MAOA and not MAOB. There is also a viewable form of the mutated protein when in crystal form with harmine, but this report concerns the unmutated form. The structure is important primarily because it allows MAOA inhibitors to covalently bond to the MAOA gene without affecting any other genes.
The protein (shown below) that monoamine oxidase A encodes for, MAO-A, is a monomer with only one chain (A). There are however four structures of this protein, and two for each type of crystal structure (harmine and clorgyline). The structure below is in crystal form with harmine, a monoamine oxidase inhibitor that only affects MAOA and not MAOB. There is also a viewable form of the mutated protein when in crystal form with harmine, but this report concerns the unmutated form. The structure is important primarily because it allows MAOA inhibitors to covalently bond to the MAOA gene without affecting any other genes.
Effects on Animals
Serotonin, dopamine, and noradrenaline are all involved in regulating aggression. One study involving mice was carried out by the Institute of Cytology and Genetics in the Siberian Branch of the Russian Academy of Sciences. They found that mice that were deficient in MAOA exhibited higher territorial, predatory, and isolation-induced aggression. The study also observed a “disruption of normal patterns of social interaction" in the mice with high levels of MAOA. Many prior studies only linked MAOA deficiency with responsive or emotional aggression, but in the 2007 study the researchers found that MAOA deficiency decreased the threshold for predatory aggression as well.
Serotonin, dopamine, and noradrenaline are all involved in regulating aggression. One study involving mice was carried out by the Institute of Cytology and Genetics in the Siberian Branch of the Russian Academy of Sciences. They found that mice that were deficient in MAOA exhibited higher territorial, predatory, and isolation-induced aggression. The study also observed a “disruption of normal patterns of social interaction" in the mice with high levels of MAOA. Many prior studies only linked MAOA deficiency with responsive or emotional aggression, but in the 2007 study the researchers found that MAOA deficiency decreased the threshold for predatory aggression as well.
Effects on Men
Note that some of the following effects may also apply to women, but they are either more prevalent or more relevant to men as the gene’s main effect on women (discussed later) will not be explored in this section.
The MAOA gene in men has been linked to many aspects of well-being, including erectile dysfunction and other abnormal sexual maturations, substance abuse, depression, social anxiety, attention deficit disorder, and many other psychiatric disorders. It follows that MAO inhibitors are used to treat severe social anxiety, erectile dysfunction, and depression among other things such as Parkinson’s Disease. Although the inhibitors are very effective, they are also controversial due to their dangerous side effects. These inhibitors are extremely strong and even lethal, so they are only employed when traditional antidepressants have failed. Mutations of the MAOA gene can also cause Brunner syndrome, abbreviated BRUNS, which is a slight mental retardation. This mutation only affects males and females carrying the mutation function normally.
Perhaps the most interesting and highly provocative piece of information concerning monoamine oxidase A relates to its linkage to male aggression and violence. The most common allele found in humans is the 3R allele, with approximately one-third of men in "Western" countries carrying this form of the gene. Although the 3R allele is thought to be related to aggression in males, the 2R allele is the form of the MAOA gene that correlates with more severe violent impulses. The violent tendencies associated with the gene are interesting in and of themselves, but the truly provocative and controversial implications of this discovery can only be realized after examining how this gene is distributed among different groups of people. The 3R allele is found in 36% of Caucasian males, 54% of Asian males, and 58% of Black males. The 2R allele is found in .00067% of Asians males, .9% of Caucasian males, and 5.5% of Black males. It is clear why these figures are controversial, as people can (and do) use this as the basis for a sort of new eugenics.
Many websites can be seen touting this information as the justification for their racist beliefs. However, one gene does not determine an individual’s entire behavior. Understanding violent and aggressive tendencies is far more complicated than locating the presence of a single gene. In a study that includes the aforementioned statistics, done by professors of psychology at Arizona State University and University of California at Berkeley, the authors note that “it is likely that the school education partly contributes to the overall age-related development” of children and their behaviors. They go on to state that factors such as peer relationships, parental warmth and positive reinforcement, parental discipline, and general parental attention have been strongly linked to behaviors such as aggression and other social behaviors. That is to say, socioeconomics (which relates to family dynamics and education) plays a major role in violent impulses, and concluding that the MAOA gene and only the MAOA gene determines aggressive behavior is objectively bad science.
Note that some of the following effects may also apply to women, but they are either more prevalent or more relevant to men as the gene’s main effect on women (discussed later) will not be explored in this section.
The MAOA gene in men has been linked to many aspects of well-being, including erectile dysfunction and other abnormal sexual maturations, substance abuse, depression, social anxiety, attention deficit disorder, and many other psychiatric disorders. It follows that MAO inhibitors are used to treat severe social anxiety, erectile dysfunction, and depression among other things such as Parkinson’s Disease. Although the inhibitors are very effective, they are also controversial due to their dangerous side effects. These inhibitors are extremely strong and even lethal, so they are only employed when traditional antidepressants have failed. Mutations of the MAOA gene can also cause Brunner syndrome, abbreviated BRUNS, which is a slight mental retardation. This mutation only affects males and females carrying the mutation function normally.
Perhaps the most interesting and highly provocative piece of information concerning monoamine oxidase A relates to its linkage to male aggression and violence. The most common allele found in humans is the 3R allele, with approximately one-third of men in "Western" countries carrying this form of the gene. Although the 3R allele is thought to be related to aggression in males, the 2R allele is the form of the MAOA gene that correlates with more severe violent impulses. The violent tendencies associated with the gene are interesting in and of themselves, but the truly provocative and controversial implications of this discovery can only be realized after examining how this gene is distributed among different groups of people. The 3R allele is found in 36% of Caucasian males, 54% of Asian males, and 58% of Black males. The 2R allele is found in .00067% of Asians males, .9% of Caucasian males, and 5.5% of Black males. It is clear why these figures are controversial, as people can (and do) use this as the basis for a sort of new eugenics.
Many websites can be seen touting this information as the justification for their racist beliefs. However, one gene does not determine an individual’s entire behavior. Understanding violent and aggressive tendencies is far more complicated than locating the presence of a single gene. In a study that includes the aforementioned statistics, done by professors of psychology at Arizona State University and University of California at Berkeley, the authors note that “it is likely that the school education partly contributes to the overall age-related development” of children and their behaviors. They go on to state that factors such as peer relationships, parental warmth and positive reinforcement, parental discipline, and general parental attention have been strongly linked to behaviors such as aggression and other social behaviors. That is to say, socioeconomics (which relates to family dynamics and education) plays a major role in violent impulses, and concluding that the MAOA gene and only the MAOA gene determines aggressive behavior is objectively bad science.
The video below is an interview with Dr. James Fallon of UC Irvine concerning MAOA.
The image on the left displays the association between delinquent behavior and age with and without the 2R allele of MAOA. The image on the right shows how MAOA breaks down chemicals inside the body.
Effects on Women
In 2012 ,the journal, Progress in Neuro-Psychopharmacology and Biological Psychiatry, published an article linking the same gene that causes aggression in men to happiness in women. The study was conducted on 193 women and 152 men. There was no correlation between the gene and happiness in men. The lead author of the study, Henian Chen, MD, PhD, described MAOA as “the first happiness gene for women.” The MAOA gene is on the X-chromosome, and thus women can have either zero, one, or two copies of the gene. Women who had one copy of the gene were happier than those who had none, while those who had two copies of MAOA were significantly happier. This recent study “points to a brighter side of this gene” that was previously only known as the “warrior gene.”
In 2012 ,the journal, Progress in Neuro-Psychopharmacology and Biological Psychiatry, published an article linking the same gene that causes aggression in men to happiness in women. The study was conducted on 193 women and 152 men. There was no correlation between the gene and happiness in men. The lead author of the study, Henian Chen, MD, PhD, described MAOA as “the first happiness gene for women.” The MAOA gene is on the X-chromosome, and thus women can have either zero, one, or two copies of the gene. Women who had one copy of the gene were happier than those who had none, while those who had two copies of MAOA were significantly happier. This recent study “points to a brighter side of this gene” that was previously only known as the “warrior gene.”
Legal Case Study
In 2007 Bradley Waldroup brutally murdered his wife, shooting her eight times. His defense lawyer, Richardson, had a forensic scientist, William Bernet, give Waldroup a psychiatric evaluation. He found that Waldroup had a high-risk version of the MAOA gene. Bernet testified in court that “His genetic makeup, combined with his history of child abuse, together created a vulnerability that he would be a violent adult.” The defense argued that the high-risk version of MAOA coupled with child abuse leads to a 400% increase in the odds of being convicted of a violent crime as an adult. It was originally assumed that Waldroup would be given the death penalty, but ultimately was on charged with voluntary manslaughter.
In 2007 Bradley Waldroup brutally murdered his wife, shooting her eight times. His defense lawyer, Richardson, had a forensic scientist, William Bernet, give Waldroup a psychiatric evaluation. He found that Waldroup had a high-risk version of the MAOA gene. Bernet testified in court that “His genetic makeup, combined with his history of child abuse, together created a vulnerability that he would be a violent adult.” The defense argued that the high-risk version of MAOA coupled with child abuse leads to a 400% increase in the odds of being convicted of a violent crime as an adult. It was originally assumed that Waldroup would be given the death penalty, but ultimately was on charged with voluntary manslaughter.
Bradley Waldroup in court
Isolating Monoamine oxidase A
The left and right primers, as well as their respective properties, are pictured above. However, our attempt in class to isolate the MAOA gene on our X-chromosome was unsuccessful.
Sources
http://www.omim.org/entry/309850?search=maoa&highlight=maoa
http://onlinelibrary.wiley.com/store/10.1002/ab.20161/asset/20161_ftp.pdf?v=1&t=hvhniv17&s=cb6956806c57f59901913bba523d3660ba904ef8
http://www.eurekalert.org/pub_releases/2012-08/uosf-sfg082812.php
http://www.rcsb.org/pdb/explore/explore.do?structureId=2Z5X
http://www.ncbi.nlm.nih.gov/gene/4128
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1832154/
https://www.youtube.com/watch?v=4osmQ7jWiow
http://www.omim.org/entry/309850?search=maoa&highlight=maoa
http://onlinelibrary.wiley.com/store/10.1002/ab.20161/asset/20161_ftp.pdf?v=1&t=hvhniv17&s=cb6956806c57f59901913bba523d3660ba904ef8
http://www.eurekalert.org/pub_releases/2012-08/uosf-sfg082812.php
http://www.rcsb.org/pdb/explore/explore.do?structureId=2Z5X
http://www.ncbi.nlm.nih.gov/gene/4128
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1832154/
https://www.youtube.com/watch?v=4osmQ7jWiow