The words “the mitochondrion is the powerhouse of the cell” are familiar to many of us. Genes, on the other hand, have always confused some of us. Some may know that gene expression is related to whether a gene is switched “on” or “off”. We may understand that genes code for proteins. But wait… recent studies conducted by Jerold Chun from the Sanford Burnham Prebys Medical Discovery Institute suggest that Advanced Placement (AP) biology may have missed something revolutionary about what we know about genes.
Okay, hold up, tell me what I should know!
Scientists first observed cells changing their DNA in the 1970s by looking at immune cells. [1] They found that these immune cells would cut out sections of their DNA which code for proteins. These particular proteins would help fight off pathogens. The immune cells would then rearrange these pieces of DNA into different combinations which, essentially, allows our immune defenses to produce a diverse set of antibodies.
Although DNA shuffling does occur, most cells in our bodies do not undergo this process. However, scientists have recently discovered that neurons in our brain do shuffle their genes. The study conducted by Chun shows that although this DNA shuffling (or recombination) increases protein combination, it may also result in Alzheimer’s disease.
How did they find this out?
Prior to Chun’s study, scientists hypothesized that somatic recombination, or genomic reshuffling, occurs in our brain. [1] They came to this conclusion because drastic differences were seen in the DNA of neurons; neurons usually have a greater difference in their genetic sequence between neurons compared to other cells which are similar to one another. However, there have not been any conclusive studies which proved this consensus up until Chun’s findings. His study particularly focused on looking at Alzheimer’s in the brain. They hypothesized that this cellular phenomenon of increased genetic shuffling in neurons could explain the formation of Alzheimer’s disease.
Chun and his team sought to analyze the neurons in the brains of seven patients who had the uninhibited form of Alzheimer’s in comparison to the brains of six healthy elderly people. The researchers chose to determine whether the neurons contained different variations of the gene for the amyloid precursor proteins (APP) which is a source of plaques (protein fragments) in the brains of peoples suffering from Alzheimer’s disease. [2]Chun’s team thought this would be a good idea because their previous research indicated that patients with Alzheimer’s disease would have extra copies of the APP gene which could be a product of somatic recombination.
The important findings
The scientists found that there were thousands of variations of the APP gene. More importantly, however, was that Chun discovered that neurons in patients with Alzheimer’s disease had about six times the amount of variation in the APP gene in comparison to the neurons in the healthy elderly brains. Chun highlights that there is a correlation between somatic recombination (gene shuffling) and the presence of Alzheimer’s. Chun puts it best when he says that “rather than having one constant blueprint that stays with us throughout life, neurons have the ability to change that blueprint.” [2]
The Image shows a brain without Alzheimer’s (left) and a brain with Alzheimer’s (right) – colours refer to the intensity of functioning parts (yellow & red = functioning)
Where does this variation come from and what can we do about it?
Chun’s team believes that gene shuffling is caused by an enzyme called reverse transcriptase which plays a part in making copies of DNA. Chun states that this “sloppy copier” (reverse transcriptase) is what results in the variation of the genes in regard to APP. What is interesting to note is that if more studies can show that Chun’s findings are credible, gene shuffling in neurons may also be heavily involved with other neurological diseases such as Parkinson’s. [3]
What is interesting though is that we have already created drugs that block these reverse transcriptase. The anti-retroviral therapy drugs are used as a part of the standard mix for treating HIV infection. Chun and his team also analyzed literature of individuals older than 65 who were taking these Anti-retroviral; they found that these individuals were almost free from Alzheimer cases thereby insinuating that this therapy can be used to treat Alzheimer patients. [2]
As Stanford students, it may be an enlightening experience to be directed on a path to solve a problem that impacts millions and their families. If you are interested in neuroscience or you particularly enjoy the possibilities of advancing Alzheimer research, you may want to visit Stanford Alzheimer’s Disease Research Center. Although I looked at only one particular disease, the study of gene shuffling in neurons may help us better understand neurological diseases; this can help us create better treatments for numerous diseases. Like Chun and his team, you never know what you may find next.
If you want to hear it from the group themselves, watch this wonderful video of Chun speaking about his research.
References:
[1] Sanford Burnham Prebys Medical Discovery Institute. (2018, November 23). Never-before-seen DNA recombination in the brain linked to Alzheimer’s disease. ScienceDaily. Retrieved from www.sciencedaily.com/releases/2018/11/181123135126.htm
[2] Leslie, M. (2018, November 21) Landmark study show brain cells revamp their DNA. ScienceMag. Retrieved from https://www-sciencemag-org.stanford.idm.oclc.org/news/2018/11/landmark-study-shows-brain-cells-revamp-their-dna-make-new-proteins-perhaps-sparking
[3] Sanford Burnham Prebys Medical Discovery Institute (2018, September 24) Thousands of DNA changes in the developing brain revealed by machine learning. Retrieved from https://sbpdiscovery.org/press/thousands-of-dna-changes-developing-brain-revealed-by-machine-learning
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