From Nucleotides to Neurons: GeneSoc to feature the Human Brain in Genetics Week 2017

By: Sean Lemuel L. Santos (Hybrizyme)

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With the theme, “Gene-Wired: Transcribing the Genetic Blueprint of the Human Brain”, The UPLB Genetics Society will feature how genetics relate to the study of the most complex organ in the body. From October 9-13, GeneSoc will fire up neurons as it conducts the Genetics Week 2017 at the Wing C lobby of the Institute of Biological Sciences in the University of the Philippines – Los Banos. It will showcase in its exhibit a wide array of relevant topics that delve deeper into the human brain through the lenses of genetics.
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The brain is the most complex organ in the body. It controls our sensations, allows us to speak, coordinates our movement, dictates when we will sleep, and many others. But deep beneath the complexity of our biological supercomputer lies the complexity of its genes. Like any other organ, the brain is a product of an expressed information – the genes-in-action. The genes explain how a baby brain develops into an adult one, what made the human brains evolve from ancestral ones, why some are nocturnal while others are early-risers, etc.

Genes are a powerful tool in studying the information behind the human brain. They are the blueprints of the brain’s architecture. By understanding the genes, we begin to see the underlying mysteries of the human brain slowly unfolding, revealing to us how all those neurons, chemicals, and hormones packed inside the human ‘light-bulb’ originates from the stretches of our DNA.

Genetics and Neuroscience

The study of the brain in the light of genetics began in the mid-20th century. It was Seymour Benzer, considered by many as the father of neurogenetics, who started to develop the field in the early 1960s by studying the brains of a fruit fly, Drosophila. One of his early researches focused on how the genes affect our sleep-wake cycle (California Institute of Technology, 2017). This cycle, also called circadian rhythms, is partly controlled by the brain along with other organs (Tortora & Derrickson, 2011).

Clock Genes

Decades after Benzer’s research, numerous studies about genes related to sleep emerged. Recent studies have found out that there is such a thing as “clock genes” – genes which affect our sleeping patterns. Scientists have discovered that these clock genes are found in a part of the brain known as the suprachiasmatic nucleus or SCN (Resnick, 2017) – the one that signals the pineal gland to drug us to sleep (Tortora & Derrickson, 2011). These clock genes in the SCN are repeatedly turned on and off in a 24-hour cycle, releasing proteins when turned on and stops when turned off (Hastings, 1998). In other words, the on-and-off cycle might be the reason why we have a sleep-and-wake cycle.

Brain Evolution

Sleep is a very essential activity both exhibited by us humans and our chimp cousins. However, what sets us apart from other primates is our ability to construct language. About a million years ago, early humans evolved to have a larger neocortex, a part of the brain responsible for language. And the reason for this could be partially attributed to a single change in the sequence of DNA. 

Marta Florio of the Harvard Medical School and her colleagues in Germany studied a gene called ARHGAP11B found in Neanderthals and Denisovans but not in chimpanzees. They found out that this gene multiplies ‘immature’ cells that would later become the neurons of the brain. The ancestor of the gene, the ARHGAP11A on the other hand, is the one found in chimpanzees and cannot do what the former does. Florio and her colleagues discovered that the ARHGAP11B gene can be turned to look like the ARHGAP11A gene by changing a single base (C into G) in the sequence. And when this happens, the ability of the ARHGAP11B gene to multiply immature cells was lost (Batsakis, 2016). This implies that the evolution of a larger brain was significantly influenced by even a single substitution of a base.

Epigenetics of Stress

When it comes to our brain’s stress response, genetics also play a key role. In one study of animal behavior, researchers have observed that rats with nurturing mothers tend to become less susceptible to stressors whereas those rats with negligent mothers tend to become the opposite. The reason for this is that, when the rats were nurtured, the genes which respond to stress become inactivated - an example of epigenetic changes or changes in which genes are turned on without necessarily changing the DNA. These epigenetic changes are reversible, meaning that the more sensitive rats could become less sensitive to stress when their negligent mothers are swapped with nurturing ones. Moreover, these epigenetic changes can be passed down to succeeding generations (University of Cambridge, 2017).

Predisposed Addiction

Addiction was once believed as a person’s own sinful decision. But recently, science has shown that addiction is not just personal and environmental but is also highly influenced by our genes. For instance, researchers have found out that a variant allele in the DRD2 gene (gene that codes for dopamine receptor) is more common in alcoholic and cocaine-addicted people. On the other, in another study using mice, it was discovered that those mice without the Htr1b gene (gene for serotonin receptor) tend to be more addicted to alcohol and cocaine (Genetic Science Learning Center, 2013)

The Aging Brain

Genes also affect brain aging. In a study done by researchers at the Columbia University Medical Center, it was found out that a gene called TMEM106B affects the aging of a brain region called frontal cortex. The frontal cortex is the one located in the frontal lobe and is responsible for higher cognitive functions (Tortora & Derrickson, 2011). In a group of people aged 65 and above, those that have two ‘bad’ copies of the TMEM106B gene have a frontal cortex that looks 12 years older than those with two ‘good’ copies of the gene. When a person reaches 65 and has two ‘bad’ copies, his/her brain responds badly to stressors and ages hastily. The opposite occurs in a person with two ‘good’ copies. The study published in Cell Systems also noted that this TMEM106B gene could be responsible for the onset of a certain type of dementia (Columbia University Medical Center, 2017).

Alzheimer’s Disease

As we age, there are numerous diseases that our brain could suffer from. One of them is Alzheimer’s disease. Characterized mainly by the loss of short-term memory, Alzheimer’s disease or simply AD is a brain disease that could also be traced in our DNA. According to the National Institutes of Health of the U.S., there is a gene called APOE which contribute to the development AD. The APOE gene has at least three different variants (alleles) namely: E2, E3, and E4. The APOE E4 allele is the one which has been linked to AD. People who have one copy of this allele have a high risk of developing AD. Meanwhile, those which have two copies are at a higher risk for AD onset. This E4 allele is linked to the accumulation of plaques in the brain tissue which could result to the death of brain cells and the beginnings of AD (National Institutes of Health, 2017).

Neuroimaging

To better understand neurodegenerative diseases like Alzheimer’s, the brain must be examined by looking into its structure. This is where an emerging technology called Neuroimaging Genetics comes into play. In Neuroimaging Genetics, the data from brain images are correlated with the data from the DNA. In other words, the phenotype (the brain) is associated with the genotype. And since people have varied genotypes, scientists can then begin to point out which of those might be causing a particular change in the brain. Surprisingly, there have been instances where even only a single change in the DNA sequence caused a huge difference in the structure of the brain (Bigos, Hariri, & Weinberger, 2016).

Intelligence Genes

If our brains become less intelligent as we age, could we possibly reverse the process? The answer to this is yes, at least genetically. In 1999, scientists at the Princeton University tried to genetically improve intelligence by inserting a gene called NR2B in mice named “Doogie”.  This NR2B gene excites the receptors in the hippocampus, a region of the brain responsible for memory (Tortora & Derrickson, 2011). As a result of the gene’s action, the mice showed better memory and more improved learning abilities. More interestingly, these mice were able to retain their intelligence unlike other mice which displayed a decline in their mental abilities (Radford, 1999).

Genes and the human brain are inseparable. The brain, being the most complex of all the organs, are traceable in the most complex biomolecule, the DNA. The genetics of the human brain reveal a deeper understanding of the brain’s development, its evolutionary history, its diseases, how it ages, and how it can be cured. And knowing this, it can surely be said that the human brain is a gene-wired architecture of nature.

References:

Batsakis, A. (2016, December 8). How a tiny genetic typo helped grow our big brain. Retrieved from Cosmos: The Science of Everything: https://cosmosmagazine.com/biology/how-a-tiny-genetic-mutation-grew-our-big-brain

Bigos, K. L., Hariri, A. R., & Weinberger, D. R. (2016). Neuroimaging Genetics: Principles and Practices. Oxford: Oxford University Press.

California Institute of Technology. (2017, May 18). Talk of the Archives. Retrieved from Archives: The Caltech Archives: http://archives.caltech.edu/talk-archive/

Columbia University Medical Center. (2017, March 15). Brain Aging Gene Discovered. Retrieved from NeuroscienceNews: http://neurosciencenews.com/genetics-brain-aging-6250/

Genetic Science Learning Center. (2013, August 30). Genes and Addiction. Retrieved from Learn.Genetics: http://learn.genetics.utah.edu/content/addiction/genes/

Hastings, M. (1998, December 19). The brain, circadian rhythms, and clock genes. British Medical Journal, 317(7174), 1704–1707.

National Institutes of Health. (2017, September 26). APOE gene. Retrieved from U.S. National Library of Medicine: https://ghr.nlm.nih.gov/gene/APOE

Radford, T. (1999, September 2). Mice given extra gene become smarter. Retrieved from theguardian: https://www.theguardian.com/science/1999/sep/02/genetics.uknews

Resnick, B. (2017, March 17). If you’re just not a morning person, science says you may never be. Retrieved from Vox: https://www.vox.com/2016/3/18/11255942/morning-people-evening-chronotypes-sleeping

Tortora, G. J., & Derrickson, B. (2011). Principles of Anatomy and Physiology. New Jersey: John Wiley and Sons.

University of Cambridge. (2017). The genetic brain. Retrieved from Cambridge Neuroscience: http://www.neuroscience.cam.ac.uk/research/cameos/GeneticBrain.php



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