‘Zom­bie gene’ pro­tects ele­phants from can­cer

The Charlotte Observer (Sunday) - - Obituaries - BY MELISSA HEALY Los An­ge­les Times

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. 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” — “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 this week 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, Lynch 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.

So Lynch’s team went look­ing for LIF (short for Leukemia 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 — 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 addi- tional 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 rec­og­nized tu­mor-sup­pres­sor mech­a­nism turned on. That, in turn, ac­ti­vated the LIF6 pseu­do­gene.

Stirred to life, the zom­bie gene pro­ceeded to carry out its grim pro­gram, mak­ing pro­teins for en­ter­ing the in­ter­nal ma­chin­ery of dam­aged cells and or­der­ing them to kill them­selves. In ele­phant tis­sue, the dam­aged cells turned them­selves in­sid­e­out, 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 tu­mors 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.


Re­searchers have dis­cov­ered a gene in ele­phants that goes to work when cells are stressed, killing the dam­aged cells. Ele­phants have mul­ti­ple copies of this “zom­bie gene,” but most other mam­mals have only a sin­gle copy of the gene and it stays dor­mant.

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