Why Don’t Elephants Get Cancer?

 

When organisms have a large number of cells, then there is a higher chance that there will be a mutation. This is not the case for large mammals, such as elephants. The P53 gene is found in a lot of mammals, including humans. This gene repairs DNA replication errors, which prevents mutations, which prevents cancerous cells from growing and spreading. It also prevents cancerous cells from turning into tumors by pausing division of cells. Humans have one copy of this gene, while it was recently discovered elephants have 20. This means that elephants can produce 40 proteins that can help elephants prevent cancer in their bodies. Cancer develops in humans when mutations prevent P53 from working. In elephants, P53 also responds quickly by molecular triggers, so it is able to quickly detect when mutations occur. 

Scientists took blood samples from elephants to observe how P53 interacted with damaged cells and compared the interactions to human P53 and damaged cells, which could be a breakthrough in understanding cancer. Perhaps there is a ratio of body size to the number of P53 genes found that determines how many P53 genes mammals will have. If P53 genes were inserted into humans, then this could reduce the chances of someone developing cancer. Another idea that I thought of relates to an exercise in Genetics Lab. When skin color was discussed, it was discovered that people with ancestors that had a lot of sun exposure had more melanin production. The melanin production protected the skin from UV rays and allowed folate vitamins to be produced when a woman was pregnant so that babies would survive. Maybe elephants were susceptible to cancerous mutations caused by UV light, and elephants with more copies of P53 were naturally selected.

Genetic Consequences of Tuskless Elephants due to Ivory Hunting

African elephants in Mozambique were being hunted for ivory which has led them to have evolved without tusks. After the Civil War in Mozambique in the late 1900s, poaching has decreased the elephant population by more than 90%. Before the war, a small percentage of elephants were naturally tuskless. However, after the war, the percentage has risen to 33% which confirms the hunting pressures on elephants in Mozambique for tusks. Tusked and tuskless elephants eat different plants which means that poaching was beneficial during the war, but not after. As a result, genetic diversity changed within female elephants with regards to the chromosome that codes for tusks. AMELX and MEP1a are the genes that are associated with the growth of incisor teeth in humans (equivalent to tusks in elephants) at which the AMELX provides instructions which makes a protein called amelogenin, which allows for the formation of enamel, the white material that forms the protective outer layer of each tooth. This is related to the tusks in elephants because the shiny white tusks that elephants have are X-linked which is fatal to males and dominant in females. This means that only one copy of the mutation is needed to cause tusklessness. The genetic mutation that resulted after the war means that humans are dominant in terms of obtaining resources through hunting and gathering and that hunting caused the mutation in elephants to produce tuskless offspring.

Elephant genetics guide conservation

 A large scale study was done in Tanzania  which show the history of elephant populations and how they interact as well as what areas may be critical to conserve in order to preserve genetic diversity. Their population have declined due to habitat loss and poaching as well as other human activities. Maintaining  connection between protected areas is important to induce gene flow which can improve their genetic diversity which will help smaller populations against diseases and other treats. Researchers have compared nuclear and mitochondrial DNA of 688 elephants in 4 major areas. These areas contain varying levels of of protection which include national parks, game reserves, and private lands conserved for wildlife tourism and livestock. As well as wildlife corridors which are the areas between these protected areas The researchers found that elephants in Lake Manyara National park  were some how similar to those in Serengeti region. Even though no physical barriers between elephants there's very limited gene flow between the two populations. They have also found that it could be from cultural or behavioral roles, they have also tracked elephants moving between the areas, however they were not mating with each other. However because of the tourism within these protect areas The Lake Manyara is now completely isolated and now only include a 100 individuals. This brings in the loss of gene flow through these areas which lead to a negative effect due to inbreeding. The way elephants create gene flow is by the males when old enough are ejected from their herd and have to  find another.

links:

https://www.eurekalert.org/pub_releases/2020-11/ps-egg111920.php

https://science.psu.edu/news/Lohay11-2020  

Elephants rarely get cancer because their bodies have a rare 'zombie gene'

 

Elephants are virtually the last mammals that have the LIF6 gene. It has died in almost every other animal, but still operates in elephants and might be able to help us find a cure to cancer. Elephants rarely every get cancerous diseases, and scientists are starting to contribute it to the fact that elephants have 20 copies of the p53 gene to turn on the LIF6 gene, whereas humans only have one so we might not have enough power to flip the LIF6 gene back on. In the study, scientists focused on refunctionalizing the LIF6 gene, which is a leukemia inhibitory factor with apoptotic  functions. Lynch and his team were originally studying the p53 gene in elephants, but found that the LIF6 gene evolved to create a new "on" switch, which enables the gene when it is exposed to other dead cells. The study concluded that once the LIF6 gene is activated by p53, it kills the cell fairly quickly and produces a protein that destroys the cell's mitochondria and kills the cell. Then the LIF6 gene was blocked in elephants in the study, the diseased cells quickly became cancerous. When the LIF6 gene was introduced to mice that didn't have the gene or just didn't have it activated, they became cancer resistant.

This study has made a huge step toward cancer research, and I hope they continue with their experiments. If scientists can prove that replacing the gene in mice does not give any long term effects, then maybe we could start using it in humans. Getting rid of cancer would be a huge accomplishment in today's world and would help so many people and families. Even if this turns out to be a temporary fix, it could give so many people a longer time to live and create better lives for people. I'm sure many people in the world would be willing to donate money to fund this research, I just wish it was a little more accessible. This article wasn't available until the second page on Fox News, but it seems like a really important story and should be pretty popular.

https://www.foxnews.com/science/elephants-rarely-get-cancer-because-their-bodies-have-a-rare-zombie-gene

The 'Zombie Gene' That May Protect Elephants From Cancer

          This past Summer an article was released revealing the findings of Dr. Vincent J. Lynch and other scientists from the University of Chicago. These scientists have discovered a rare mutation in the genes of elephants while looking for a reason behind their small probabilities of cancer. This rare mutation starts in the p53 gene. The p53 gene, in short, is a tumor suppressant gene that inhibits the formation of tumors. p53 makes a protein that senses damaged DNA and responds by either repairing or by destroying the damaged cells.

          The evolved p53 gene in elephants reacts differently because when the protein senses damaged DNA, it does not even think about fixing it, the protein just automatically destroys them so they will not have a chance to reproduce their mutation. Not only do their p53 genes immediately eliminate the problem, but they also have so many more than humans. Humans only have one copy of p53 while elephants have 20 copies.
          The variation in the p53 gene sparked scientists to look a little deeper, which unearthed a very interesting mutation that explains why elephants are not as prone to cancer. Both humans and elephants have a gene called LIF. While humans have only one LIF gene, elephants seem to contain 10. After looking closer into these LIF genes scientists discovered one LIF6 gene, which is a gene that has been seen before in animals, but has been thought to have become extinct up until this discovery in modern day elephants. LIF6 has seemingly 'resurrected' itself, which is why scientists are referring to it as the 'Zombie Gene'.
          Normally when the proteins are released from the p53 gene, LIF genes are instructed to stop each damaged cell's production of proteins. However, LIF6 mutated in order to be able to read the protein made by p53, which makes LIF6 able to go in and actually kill the damaged cells instead of just impeding their ability of making proteins. LIF6 kills the cell by attacking the mitochondria, which turns out to be very poisonous to the cell. The mitochondria is ripped open, poisons the cell, and ultimately kills the cell.
          Although there are still many factors to look into, I think it is a wonderful beginning to a major study on the way the LIF6 gene works. To be able to see this gene live and in action could be very beneficial to discovering what we can do as far as medication in humans. I think this study could be the catalyst to many others in order to see what can be done to manipulate the gene in order to possibly take down one of the biggest forms of disease in our world today.

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Dead but Not Forgotten: Elephant Genomic History

A study conducted by scientists at The University of Texas at Austin recently sequenced the genomes of 14 living and extinct elephant species to try and understand the potential gene flow within this group. This was done by mapping out the genome of living species such as the African forest elephant, the Savanna elephant, the Asian elephants, along with other like species, and then compared them with the genome of extinct species such as the woolly mammoth, the straight-tusked elephant, and the American mastodon. By doing this they were able to see the decent pattern of modern day elephants. One of the many things they discovered was that the straight tusked elephant, which went extinct approximately 120 thousand years ago, and the present-day forest elephants dissented from a related lineage.  Additionally, we have come to learn that in both past and present elephant genomes there seems to be a high amount of hybridization which has led to the group’s current speciation. 

One of the more notable discovers that came from this study was that African forest elephants and the Savanna elephant appeared to have diverged over 2 million years ago and have been genetically separated for around 500 thousand years. This discovery’s significance lies in the fact that it ends the debate of whether these two types of elephants are separate species which, evidently, they are. Because of this, these two groups of elephants can now receive more effective conservation efforts, as they can be specifically geared, and funded, to the individual species environmental resource requirements, and threats (Daley). With the advancements in genomics, both in efficiency and accuracy, demonstrated here with the successful mapping of the elephant’s genome, its applications and implications are vast and profound to say the least.

The article can be found at https://www.the-scientist.com/?articles.view/articleNo/51918/title/Extinct-and-Living-Elephants--Genomic-History-Sequenced/

And here is the link to the original study that http://www.pnas.org/content/early/2018/02/16/1720554115

This Just In: Study Shows That Boys are Stupider

A recent article published in the New York Times explored the correlation between being male and dying by falling into natural traps.  This study was conducted by multiple universities around the world on woolly mammoths from Siberia and South Dakota.  The study consisted of analyzing genes to determine gender.  In order to make sure that the results were precise and accurate, the researchers analyzed the genes from bones, teeth and tusks.  All results concluded that more than half of the woolly mammoths that died were male.  All the woolly mammoths were found buried on what was described as "natural traps."  Once males hit maturity between the ages of 14-16, they would leave their mothers and either wander off alone or find a newly made group consisting of young males that had just hit maturity.  Scientists hypothesized that the large number of male mammoths that died was a result of the young males being inexperienced and finding themselves in dangerous situations without the help of their experienced mother.  These studies did not analyze other parts of the mammoths' genomes, which could possibly be the study's largest downfall.  By omitting the analysis of other genes, the researchers cannot be as certain as they can be that these deaths were solely based on the lack of experience in young males.  This research is very important in arguments with men and boys because it allows women to cite their sources and have a scientific basis for their arguments.  Men and boys, on the other hand, do not have scientific evidence for anything.  Because their men and boys, and look where that got these woolly mammoths. Here is another article from a different news outlet that is reporting on the same research so you all know that I'm not lying about this.

Possible Re-write of the Elephant Family Tree

For many years, scientists thought they had the elephant family tree mapped out. However, a recent discovery of an ancient elephant fossil forces scientists to rethink the family tree.

What we know now is that there are three species of modern elephants:
1. The Asian Elephant (Alphas maximus)
2. The African Elephant- forest dwellers (Loxodonta cyclotis)
3. The African Elephant- Savannah (Loxodonta africana)

Straight Tusked Elephant (Paleoxodon antiquus)

We also know that scientists believed the ancient predecessor, the Straight Tusked elephant (Paleoxodon antiquus) was the closest relative to the Asian elephant. But new research shows that the predecessor is actually more closely related to the African forest elephants. Even more new research of the mammoth genome reveals that mammoths and elephant species were known to interbreed in the past. This means the elephant family tree will need to be minimally altered.

What we know about the Straight Tusked elephant:
The Straight tusked elephant lived in European forests until 100,000 years ago.
Straight tusked elephants and mammoth species have interbred.
Straight tusked elephants have interbred with Asian elephants.
Straight tusked elephants represent the oldest whole genomes from a warm environment.


The greatest fascination about the elephant genome is that the Straight tusked elephant genome wasn't just sequenced, it was sequenced in such high quality, that each letter was sequenced on average
15 times, leaving many scientists in complete awe.

For more about the interbreeding of the mammoth and elephant: http://www.iflscience.com/plants-and-animals/scientists-successfully-insert-woolly-mammoth-dna-elephant-genome/

 

Gene in Elephants Reduces the Chance of Cancer

In recent studies, scientists have finally discovered a possible gene that allows the prevention of cancer in elephants. This could mean potentially a gene to prevent cancer in humans.

Elephants are noticeably larger than humans, which means they have thousands of more cells than us allowing for the potential to have cancer to be increased, however, they live about as long as humans if not longer and few get cancer. After a sample of elephants across zoos in america were studied, it was found that only about 5% of elephants had cancer as compared to 11%-15% of humans get cancer. Two teams of scientists have taken this information even further and discovered that in observing and researching elephant genes, a gene mutation is what is suppressing the cancer cell. Two types of elephants observed (African and Asian) and both species had 20 copies of the P53 gene (this gene is known to have tumor-suppressing qualities), where as humans and smaller species only have one copy of the P53 gene.

This discovery does not allow for the cancer to be treated or allow for much discovery just yet, however the more they research the P53 gene the more they are finding out about how it relates to the suppressing of cancer and tumors. Some doctors already have been studying the P53 gene and have been using it in immunotherapy treatments to fight cancer. It will be a long time before this research is useful clinically for patients however baby steps will lead us in the right direction in hopes for a cure to cancer.

Link to article:
http://www.popsci.com/this-gene-prevents-elephants-from-getting-cancer

Link to supporting article:
http://www.popsci.com/this-gene-prevents-elephants-from-getting-cancer

Why is Elephant Cancer Rare? Answer Might Help Treat Humans

On Thursday, October 8, 2015 in the Journal of the American Medical Association, new studies were published about a cancer suppressing gene found in elephants and many other species.  Dr. Schiffman, a pediatric cancer specialist at the University of Utah, lead a team of researchers in a dealing with p53, a gene that prevents cancer in elephants as well as humans and other species.  Elephants possess a vast amount of p53 compared to humans and other species smaller than them.  This is because of a condition possessed by elephants called Li-Fraumeni syndrome (a syndrome that increases an elephant’s chance of developing cancer).  This syndrome is also found in other species including humans.  The p53 gene in species possessing it, cause unhealthy cells to self-destruct when affected with radiation or other carcinogens.  Dr. Schiffman’s team made comparisons of the effects of radiation to the cells of elephants, cells form ten healthy humans and ten human patients with Li-Fraumeni syndrome.  It was found that cells of the elephants self-destruct at a rate two times faster than that of healthy humans and humans with Li-Fraumeni syndrome.  This is because of the vast amount of copies of the gene that elephants possess.  Humans have only one gene compared to the elephants’ twenty copies.  Although cancer is rare in elephants, it does not mean that it does not exist.  Schiffman’s team found that although elephants sometimes live as long as humans do, only 1 in 20 dies of cancer as opposed to 1 in 4 humans dying from cancer.  

These findings can aid in gene therapy as well as help with the development of new drugs to treat those with cancer.  This could also be a breakthrough to help many with the many different cancers that are inherited from generation to generation. 

To read more click here or here 

Elephants Could Help Prevent Human Cancer

        Can elephants lead us in the right direction to prevent cancer? How can elephants help us? Since elephants are much larger in size than us and have more cells would not they have a higher risk of being diagnosed with cancer? In theory it is thought that the bigger an animal and the more cells they have the would have a higher increase of gene mutations during cell division. These gene mutations would then result in cancerous cells. However that is not true, at all. The fact that there is no correlation between the risk of cancer and an animal's size or lifespan is also known as Peto's Paradox. A great example of this lack of correlation is that although elephants are much larger than humans, elephants have a much lower risk for cancer.
       What is it about elephants that makes them insusceptible to have cancer? A new study done by Dr. Joshua D. Schiffman from the University of Utah School of Medicine and his colleagues have just published their work on answering this question. Their study focused on a disease and cause of death for 36 mammalian species including Asian or African Elephants. Humans and elephants can both inherit a rare condition known as LiFraumei syndrome. LiFraumei syndrome substantially increases the risk of cancer. The team found that elephants have 20 or more copies of TP53. TP53 is an important tumor suppressor gene. In comparison, humans only possess one copy of TP53, with two alleles (one from each parent). However humans with LiFraumei syndrome only have one functioning allele of the TP53. Having only one allele of this major tumor suppressor gives them a 90% to 100% lifetime risk of developing cancer.
       The TP53 gene is crucial because it is a part of responding to damage to DNA by forming apoptosis via the p53 protein. Apoptosis working correctly is very critical when dealing with cancerous cell. If apoptosis does not work correctly it could result in cancer cells not being eliminated but instead persisting and becoming immortal. Elephants having more copies of TP53 and apoptosis conducted by p53 protects them against cancer. The study is still being conducted but these findings are a step in the right direction.
         I thought this article was very interesting. When trying to find out more information about cancer in humans, I would have never thought to research elephants. However being the risk of cancer in elephants is lower than humans it does make sense. I am hoping there is a way geneticists can use these studies to copy the TP53 genes to suppress tumors such as cancer. This study definitely gives us insight on why humans are so susceptible to developing cancer.

You can read the full article here!

WOOLLY MAMMOTH DNA SUCCESSFULLY SPLICED INTO ELEPHANT CELLS

In effort to bring back woolly mammoths (a process called de-extinction), geneticists at Harvard used a tool called CRISPR to splice certain woolly mammoth genes and put them in an Asian elephant’s genome. It worked and the mammoth’s genes were functional in the elephant. The team’s next goal is to make elephant/mammoth hybrid embryos and grow them in artificial wombs (because having an elephant give birth to it is not as ethical). Then, if the creature survives, they want to make it so it can survive in cold temperatures. Although it will not purely be a woolly mammoth, it will look very similar and have the same ecological niches as they do, which is close enough.

I find all of this good and bad. It is good in the way that mammoths live in cold climates while elephants live in hot. Because there are so many people where elephants live, there are many problems that elephants today face, including extinction. There are not as many humans in the colder areas, so they would be safer there. However, ecosystems in colder climates have adapted to life without mammoths a long time ago. If they were brought back, how would the rest of the organisms be affected? Would there be enough food for the mammoths and competing predators?

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