The Elephant is known to be the largest terrestrial mammal alive today. Currently existing as 3 subtypes (originally 2), African Bush Elephant, Asian Elephant, African Forest Elephant. Though all three have the same roots, Asian elephants are far more closely related to the woolly mammoth.
Having an average lifespan of 70 years and weighing in at around 6000 kgs, they are clearly animals that you do not want to mess around with. Having such a large mass means a hell lot of cells.
Cells make up all living creatures including these elephants and more cells mean more cell divisions which by default means more cellular errors and at some point, cancer should step in. Elephants have more potential cancerous cells than humans, simply because of their larger size, and yet when an analysis is done humans have a higher likely hood of suffering from cancer than elephants.
Hypothetically if an animal has more cells than a human and lives long enough, it should have a higher likely hood of getting cancer. Less than 5% of captive elephants get cancer, whereas 11 to 25% of humans get cancer. This is called Peto’s Paradox when size does not correlate with the cancer incidence. (Note that today we know there is no correlation between body size and cancer, all thanks to the mysterious workings of “mother nature”/ evolution.)
Yes, the cells are different, man and the elephant are different, but our cells probably have the same molecular machinery, the same overall genetics, then what is different. As per logic, it was believed if something is larger (and lives long enough) its likelihood of succumbing to cancer should also be equally large.
When scientist began to investigate the matter in the year 2016 Geneticist Vincent Lynch published his findings that first provided an answer to this matter of Pepto’s paradox. In this paper, he wrote that his team and he found that the elephants had more copies of the tumour suppressor TP53 gene. Twenty times more!
Humans have only one pair, whereas elephants have 20, it is probably a coincidence of evolution that something so large would have so many more copies for its protection. These increased number of copies are actually transcribed and function due to their higher number far better than human genes at tumour suppression and causing apoptosis. Usually, all copies may not be allowed to be active in other kinds of genes, but that is not the case here.
TP53 the guardian of the genome simply guards the elephant genome better than our Homo sapien genome.
Do not be disappointed though for other studies have shown that when something similar was artificially tried in mice there appear to be certain limitations that this TP53 puts on that organism in the form to reduced development, as well as developmental delays. Somehow the elephant lineage has managed to override this. More TP53 means elephant cells are extremely intolerant to DNA damage, which may not always be a good thing. In our artificially created cocoons we humans experience DNA damage all the time. We cannot afford to have cells dying left and right.
But this is not all that has allowed elephants to survive cancer.
Every now and then a few annoying genes like to simply jump around and randomly replicate themselves, we do not know why it happens. (And no TP53 is NOT one of them). And sometimes these genes for some reason are deactivated, never to come back to life again. We call them Pseudogenes.
In the elephant too, such a thing happened at some point, the gene was LIF6, leukaemia inhibitory factor. But somehow mysteriously this deactivated pseudogene in them came back to life, literally like a zombie, and that is what the scientific community calls it, Zombie Gene. They have many of these deactivated genes but have their cells have found some mechanisms to turn it back on again, and they function as tumour suppressor genes.
The TP53 gene activates the zombie gene LIF which pokes holes in the mitochondria and causes apoptosis. Those who know the apoptotic pathway will know well how this is possible.
Currently these are the 2 ways we know the elephant cells use to protect against cancer, but I am sure that there are even more yet to be discovered. I now sit back and wonder of the Dinosaur cells had similar mechanisms or not? We know that they too suffered from cancer just like the primitive man, but we do not know of the frequency or the incidence of this cancer. if oonly we had a time machine to go back in time and gather some samples.
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In pic Steve Irwin(b:1962, d:2006) One of the greatest wildlife conservation experts of our time.
You can follow his son here for stunning images of wildlife: Robert Irwin
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For further reading:
1) JAMA. 2015 Nov 3;314(17):1850-60. doi: 10.1001/jama.2015.13134.
2) Elife. 2016 Sep 19;5. pii: e11994. doi: 10.7554/eLife.11994.
3) Cell Rep. 2018 Aug 14;24(7):1765-1776. doi: 10.1016/j.celrep.2018.07.042.
A Zombie LIF Gene in Elephants Is Upregulated by TP53 to Induce Apoptosis in Response to DNA Damage.
Good one Raghu .!!
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