Elephants have not evolved into the giant animals we know today until they have successfully converted some of their genetic waste into a unique defense weapon against multiple tumors.

Elephants, both current and extinct, have succeeded in developing many factors to support the massive growth in their bodies. These adaptations and evolutionary mutations include some genetic mechanisms that have made them less susceptible to various types of cancers.

Elephants and some other "big" animals are less likely to have cancer, indicating that they have developed many ways to protect themselves against the disease.

A recent study showed how elephants succeeded in doing so: they recycled an old gene that had stopped functioning to raise the sensitivity of elephant cells to its DNA damage, allowing them to get rid of cancer cells too early.

Cells in multicellular animals undergo many stages of growth and division. At each stage of division, cells copy their entire genomes, and here some unavoidable errors occur.

Some of these errors and mutations may lead to cancer.

Some may think that the size of some large animals and their relatively long life span make them more susceptible to various cancers, but this is not what researchers see when comparing different species and races in a long line of sizes: cancer susceptibility does not necessarily relate to Cells in the object or its potential life span.

In fact, scientists have found the opposite of those quite common predictions. They found that large mammals living for relatively long periods had a low risk of cancer, and the incidence of these infections was very low.

In the 1970s, a cancer epidemiologist (Richard Bettow), now a professor at the Center for Medical Statistics and Pathology at the University of Oxford, represented this sudden phenomenon, known as the Beto paradox: Elephants do not have high rates of cancer, they have developed special mechanisms to inhibit cancer

                                      

        Richard Bettou, biologist - Photo: Cathy Harwood

In 2015, Joshua Schiffman, at the University of Utah at the Faculty of Medicine, and Carlo Malle at the Arizona State University, led a team of researchers who succeeded in showing that the elephant genome contained about twenty additional copies of the gene P53, which is a tumor suppressor, and suggested that additional copies of this p53 gene may interfere with the elephant's ability to fight and refute cancer.

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 Lisa Abiglene, a cellular biologist at Utah University School of Medicine who also contributed to the above study, is leading a project to see if additional copies of the p53 gene for elephants have other functions.

Additional copies of the p53 gene are not the only protection resources for elephants. A new research led by Vincent Lynch has shown that elephants and their relatives, which have relatively smaller bodies such as the "rock rabbit", "armor" and "terrestrial pigs" Additional copies of the LIF gene - an abbreviation of Leukemia Inhibitory Factor - which has leukemia inhibitors. This gene usually enters the protein in reproductive and reproductive functions and stimulates the growth of embryonic stem cells.

Vincent Lynch, a geneticist at the University of Chicago, has shown that one of the reasons why elephants were able to develop bodies of this magnitude was that one of their pseudogenes, Pseudogenes - a lost version of a gene inherited from ancestors - suddenly acquired a function - Picture: Courtesy of Vincent J. Lynch

Lynch presented the results of his work at the Pan-American Society for Evolutionary and Evolutionary Biology in Cagliari in August 2017. Eleven versions of the LIF gene were found to vary from one to another, but they were all incomplete: at least They all lack the primary mass of protein coding information and the catalytic chain to regulate gene activity. Lynch's deficiencies suggested that none of these replicas would be able to perform the normal functions of the LIF gene, or until the cells in the body were able to represent it.

But when Lynch looked at the cells, he and his team of researchers found a series of DNA that appeared to be a binding site for the p53 protein, which led them to conclude that p53 (but not one of its replicates) LIF6, this intuition and hypothesis that was confirmed after performing experiments on elephant cells.

Further in-depth studies have shown that LIF6 causes cell death by leaking into membranes surrounding the mitochondria. To find out more about the evolutionary history of a leukemia inhibitor gene and its corresponding copies, Lynch found a similarity in nearby species of elephants: , And (rock rabbits), and (pollutants) and extinct (mastodons).

The results obtained indicate that this gene has been reproduced seventeen times, and has been lost fourteen times during the evolutionary history of elephants.

Both the sea sheep and the rock rabbits have copies of the LIF gene, but p53 appears only in living and extinct elephants, suggesting that the p53 reincarnation occurred late in evolutionary history.

Elephants are also relatives of large mammal-like animals (close to the picture), as well as small ones, such as rock rabbits (left), land pigs and armor, and elephants have begun to develop large bodies About 30 million years ago - Photo: Bjørn Christian Tørrissen and Jim P. Reid / USFWS

ynch found that most of the replicates and copies of the LIF gene were false genes - they were old genes, mutant, and useless copies of the genes that remained in the genome by chance - no more. The exception was in the sequence of the LIF6 gene, which, unlike other genes, Throughout its evolutionary history no random mutations have been acquired, suggesting that natural selection has preserved it well.

"We believe that the LIF6 gene is a false gene that has been re-activated and acquired new functions," Lynch says. "The elephants' LIF6 gene evolved from a pseudogenous gene inherited from its predecessors into an effective gene with an effective function. : "Because he came back from death, and plays a big role in the death of cells, we call it the name of the (zombie)".

Although the sea sheep and the rock rabbits have additional copies of the LIF gene, only the modern and extinct elephants possess the LIF6 gene, suggesting that they evolved only after elephants separated from their relatives of these species

The development of protection and prevention of cancer may be in the interest of all animals, so why have not all of them reactivated the LIF6 gene?

A study published in 2009 suggests that the LIF gene is essential for implantation and implantation of the fetus in the womb. Since LIF activity is controlled by the p53 gene, they together regulate reproductive activity

When the same type of gene has the same functions (as in refuting cancer and reproduction), there is likely to be a direct contradiction between them, a phenomenon called genealogists: the name Antagonistic Pleiotropy.

According to Mali, "elephants may have overcome or solved the problem of multiple antagonistic phenotypes by replicating and copying the p53 and LIF," according to Mali. "Some copies of p53 and LIF are necessary for fertility, while other pairs of these genes What is necessary in order to fight cancer, "he said, adding that the gene replicas and copies" allowed elephants to become better in fighting and refuting cancer while maintaining their fertility, enabling them to develop and build large bodies. "

Bats are not large-bodied animals, but some species live for decades, making some scientists investigate whether they also have their own anti-cancer mechanisms - Sue: Ann Froschauer / USFWS

The development of additional p53 and LIF versions may have helped elephants overcome Bito's paradox, but this can not be the only solution: some other large animals, such as whales, have only one copy of the p53, and one copy of the LIF.

Lynch and his team are now exploring the way that whales and bats have solved the Pythro paradox. Although they are not large objects, some species of bats live for up to 30 years, making researchers believe species that have a long period Life may also develop mechanisms to inhibit and refute cancers that lack short-lived ones as well.

Tracking Cancer Evolution Cell Cell:

Male also works to unravel the mystery of the way whales have solved the Pito paradox. Although the whales do not have additional copies of the p53 gene, Mali says, "We think there has been a lot of selection And evolution in the history of the p53 gene. "Mali believes that a better understanding of how large-bodied animals (Pietro's paradox) may have applications to human health is, he says," this is our first goal. Our hope is that by observing how evolution has been successful in preventing cancer, we may be able to translate this into better protection against cancer in humans. K.

Perhaps every organism that has developed a huge object has a different and distinct solution to the paradox. There is also a collection of discoveries that lie there in nature waiting for us to show us the means to prevent cancer. "

Sources

Location    Quanta Magazine 

By Sufian Ashy    

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