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‘Zombie gene’ in elephants prevents cancer

‘Zombie gene’ in elephants prevents cancer

Maybe it’s the elephant’s genes that never forget. In addition to having great memories, elephants are known for having a very low incidence of cancer.

In what might seem a wild mash-up of the SyFy channel and National Geographic, new research has uncovered a surprising factor that protects elephants against the dread disease: a gene that had gone dormant in their mammalian ancestors, but got turned back on as their evolving bodies grew ever bigger.

Scientists call it a “zombie gene” – cue the chilling music here – “a reanimated pseudogene that kills cells when expressed”.

The zombie gene is not just a curiosity.

Along with elephants, several kinds of whales, as well as bats and the naked mole rat, share enviably minuscule rates of cancer.

Biologists suspect that each of those species has evolved a different strategy to ward off malignancies, and they want to understand them all.

In time, they might find ways to approximate those strategies in humans and drive down our vulnerability to cancer.

“That’s not easy,” said Vincent J. Lynch, who led the research published in the journal Cell Reports.

Nor, he added, would it always be safe. After all, mechanisms that thwart fast-growing cells or turbocharge cellular-repair machinery have evolved over countless generations in fine balance with other checks and balances, he said.

Transfer one of these mechanisms willy-nilly to another species, and it would very likely run amok, he said.

“But if you don’t do the research, you’ll never know,” added Lynch, a geneticist and evolutionary biologist at the University of Chicago, United States.

So his team went looking for LIF (short for Leukaemia Inhibiting Factor) genes in 53 mammals, including the African elephant, the bowhead and minke whales, bats and naked mole rats.

In most species, they found a single active LIF gene. But in the modern African elephant – as well as in the manatee and the rock hyrax, both distant cousins of the elephant – they found between seven and 11 additional copies of the LIF gene, called pseudogenes.

In every species but the elephant, these LIF genes and their extra duplicates were inactive: That is, they didn’t turn on or off to produce proteins. If they had been active in the past, their function had been phased out.

In the march of evolution, they had fallen by the wayside and been left for dead, like vast stretches of every species’ genomes.

But in the elephant, Lynch and his colleagues saw that one of the additional copies of the LIF gene was active.

When the researchers induced cell stress – a step that would have led to cancer in most other animals – a widely recognised tumour-suppressor mechanism turned on. That, in turn, activated the LIF6 pseudogene.

Stirred to life, the zombie gene proceeded to carry out its grim programme, entering the internal machinery of damaged cells and ordering them to kill themselves.

In elephant tissue, the damaged cells turned themselves inside-out, and cancer was thwarted before it could gain any momentum.

And when the researchers suppressed the action of the LIF6 “zombie gene”, they found that stressed cells were more likely to form tumours in elephant tissue.

“It’s a fascinating study,” said molecular and cell biologist Vera Gorbunova of the University of Rochester in New York, who has studied the mechanisms by which naked mole rats thwart cancerous cells.

The collective research of Lynch’s group “also raises intriguing questions”, said Gorbunova, who was not involved in the new work.

The group has offered evidence that in their evolution, all complex creatures have made trade-offs, such as taking on genes (including anti-cancer genes) that increase their life span, but reduce their reproductive prowess, or vice versa.

The reanimation of the LIF6 gene may be one way in which elephants have countered what would seem to be a growing threat as they evolved to become bigger, said Lynch.

How? Biological reasoning would suggest that bigger animals would have a greater propensity than very small ones to develop cancer – mainly because they are made up of more cells.

Theoretically, the more cells there are, the higher the odds that one or more will go rogue and seed a tumour.

That is true within species: big dogs (and tall humans) are more likely to develop cancer than smaller members of their species.

But strangely, very large species are not, in general, more likely to develop cancer than are small species – an observation made by epidemiologist Richard Peto that has come to be known as Peto’s Paradox.

In part, “elephants and their extinct relatives (proboscideans) may have resolved Peto’s Paradox” by giving LIF6 new life as a killer of would-be cancer cells, wrote Lynch and his colleagues.

Apparently, not all zombies are to be feared. – Los Angeles Times/Tribune News Service

My grandmother was Italian, so where are my Italian genes?

My grandmother was Italian, so where are my Italian genes?

Maybe you got one of those find-your-ancestry kits over the holidays. You’ve sent off your awkwardly collected saliva sample, and you’re awaiting your results.

If your experience is anything like that of me and my mum, you may find surprises – not the dramatic “switched at birth” kind, but results that are really different from what you expected.

My mum, Carmen Grayson, taught history for 45 years – secondary school and university – retiring from Hampton University, Virginia, United States, in the late 1990s.

But retired history professors never really retire, so she has been researching her family’s migrations, through both paper records and now a DNA test.

Her father was French Canadian, and her mother (my namesake, Gisella D’Appollonia) was born of Italian parents who moved to Canada about a decade before my grandmother was born in 1909.

Last fall, we sent away to get our DNA tested by Helix, the company that works with National Geographic. Mum’s results: 31% from Italy and Southern Europe. That made sense because of her Italian mother.

But my Helix results didn’t even have an “Italy and Southern European” category.

How could I have 50% of Mom’s DNA and not have any Italian? We do look alike, and she says there is little chance I was switched at birth with someone else.

We decided to get a second opinion and sent away to another company, 23andMe. We opened our results together and were just as surprised.

This time, I at least had a category for southern Europe. But Mum came back as 25% southern European, me only 6%.

And the Italian? Mum had 11.3% to my 1.6%. So maybe the first test wasn’t wrong.

But how could I have an Italian grandmother and almost no Italian genes?

To answer this question, mum and I drove up to Baltimore to visit Dr Aravinda Chakravarti of the Johns Hopkins University School of Medicine and the Bloomberg School of Public Health, who has spent his career studying genetics and human health.

“That’s surprising,” he told us when we showed him the results. “But it may still be in the limits of error that these methods have.”

The science for analysing one’s genome is good, Dr Chakravarti said. But the ways the companies analyse the genes leave lots of room for interpretation.

So, he said, these tests “would be most accurate at the level of continental origins, and as you go to higher and higher resolution, they would become less and less accurate”.

As in my case, the results got me to Europe, just not Italy. My 23andMe test also showed less than 1% of South Asian, Sub-Saharan African, and East Asian and Native American.

This, Dr Chakravarti said, is likely true because the genetics of people on a continental level are so different, and it’s not likely that South Asian will look like European.

“Resolving a difference between, say, an African genome and an East Asian genome would be easy,” he said. “But resolving that same difference between one part of East Asia and another part of East Asia is much more difficult.”

I also learned that even though I got half of my genes from mum, they may not mirror hers.

DNA, genes, ancestry, DNA test, lineage, Gisele Grayson, Carmen Grayson, Star2.com

As mother and daughter, Carmen Grayson (left) and Gisele thought their DNA ancestry tests would be very similar. Boy, were they surprised. — TNS

We do inherit our genes – 50% from each parent. But Elissa Levin, a genetic counsellor and the director of policy and clinical affairs of Helix, says a process called recombination means that each egg and each sperm carries a different mix of a parent’s genes.

“When we talk about the 50% that gets inherited from mum, there’s a chance that you have a recombination that just gave you more of the northwest European part than the Italian part of your mum’s ancestry DNA,” she said.

That is also why siblings can have different ancestry results.

The companies compare customers’ DNA samples to samples they have from people around the world who have lived in a certain area for generations.

The samples come from some databases to which all scientists have access, and the companies may also collect their own.

“We’re able to look at, what are the specific markers, what are the specific segments of DNA that we’re looking at that help us to identify, ‘Those people are from this part of northern Europe or southern Europe or South-East Asia’,” Levin said.

As the companies collect more samples, their understanding of markers of people of a particular heritage should become more precise.

But for now, the smaller the percentage of a population within a continent that is in the database, the less certain they are. Helix chooses not to report some of those smaller percentages, Levin said.

23andMe reports results with a 50% confidence interval – they’re 50% sure their geographic placement is correct.

Move the setting up to 90% confidence, meaning your placement in a region is 90% certain, and that small 1.6% of my ancestry that is Italian disappears.

The ancestry tests also have to take into account the fact that humans have been migrating for millennia, mixing DNA along the way.

To contend with that, the companies’ analyses involve some “random chance”, as Levin put it. A computer has to make a decision.

And the ancestry companies have to make judgment calls. Robin Smith, a senior product manager with 23andMe, said their computers compare the DNA with 31 groups.

“Let’s say a piece of your DNA looks most like British and Irish, but it also looks a little bit like French-German,” he said. “Based on some statistical measures, we’d decide whether to call that as British-Irish or French-German, or maybe we go up one level and call it northwestern European.”

What does he think explains my case?

“It was a bit surprising,” he said. “But in looking at the fact that you have some southern European and some French-German, the picture became a little clearer to me.”

So, for now, my Italian grandmother doesn’t show up in these tests.

No matter – Dr Chakravarti, Levin and Smith all say to let the results add to your life story. The DNA is just a piece of what makes you, you. – Kaiser Health News/Tribune News Service

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