Zombie gene helps elephants guard against cancer

The riddle would make a fine beginning to one of Rudyard Kipling’s Just So Stories: how did the elephant grow so magnificently large?

The answer, research now suggests, rests in part on a socalled ‘‘zombie gene’’ that has helped to make the largest land mammal exceptionally resistant to cancer. Elephants have about 100 times as many potentially cancerous cells as humans, but while about one in six humans will die of the illness fewer than one in 20 elephants succumb.

At first glance, it makes little sense. When a cell divides it risks accumulating mutations that may lead to cancer. Larger animals have more cells and tend to live longer than smaller ones, giving them more time to gain mutations, so should be more vulnerable. The logic holds for members of the same species: small dogs rarely get cancer while large dogs do. Between species, however, cancer rates do not correlate with the number of cells, a phenomenon known as Peto’s paradox.

Researchers at the University of Chicago and the University of Utah, working separately, began to study the elephant’s cancer defences three years ago. They knew that humans had one copy of a tumour suppressor gene p53, which recognises DNA damage, a precursor to cancer, and then causes damaged cells to die. They found that elephants had 20 copies of p53.

Researchers identified another aspect of the elephant’s cancer defence: a gene that appears to have ‘‘died’’ and come back to life. They found a former pseudogene in elephants called leukaemia inhibitory factor 6 (LIF6) that had evolved an ‘‘onswitch’’. Returned from the dead, when activated by p53, it responded to damaged DNA by killing the cell, thereby guarding against cancer. – The Times