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The key to the mystery of rapidly evolving genes was found in the "junk DNA"

A long-standing puzzle in evolution is the reason why new genes, which seem to emerge from nowhere, can quickly take on functions essential to the survival of an organism.

A new study on fruit flies may help solve that riddle. It shows that some new genes become decisive because they regulate a type of DNA called heterochromatin. Once considered “junk DNA,” heterochromatin actually does a lot of important work, including acting as a heavily guarded prison: it locks in the genes of the “bad actor,” preventing them from igniting and doing damage.

Heterochromatin is also one of the fastest pieces of DNA in the body, so the genes that regulate it have to adapt quickly just to keep up, evolutionary biologist Harmit Malik at the Fred Hutchinson Cancer Research Center in Seattle and colleagues report in November 10 line in eLife.

“The work is a milestone,” said Manyuan Long, an evolutionary biologist at the University of Chicago who did not participate in the research. "It's really amazing to see such an important role that heterochromatin plays in gene evolution."

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Scientists have documented many cases of genes that appear to emerge from scratch and give an organism a new ability. For example, one of these genes in fish makes a new antifreeze protein; another in flies is essential for flying.

About a decade ago, researchers discovered that new genes not only confer new functions; some may be necessary for survival. In the Drosophila melanogaster fruit fly, up to 30 percent of the essential genes are “new,” some emerging just 3 million years ago, a flash on evolutionary time scales. The discovery overthrew the belief that important genes do not change much over evolution.

Malik’s team investigated a large family of genes in fruit flies that regulate other genes, activating them and turning them off for various tasks in the cell. He found that within the family of about 70 genes, the fastest-evolving genes were more likely to control essential functions for the fly. In fact, 67 percent of rapidly evolving genes were essential compared to 20 percent in the slower-evolving group.

“The dogma is completely the opposite of what one would expect,” Malik said.

The team discovered that one of the new essential genes, nicknamed Nicknack, emits instructions for a protein that binds to heterochromatin, although details remain unknown.

To see how quickly Nicknack was able to take on an essential role, the researchers replaced the Nicknack gene in D. melanogaster with the Nicknack gene in its closest evolutionary relative, D. simulans. The two species of flies split into two branches of the fruit fly tree about 2.5 million years ago. Scientists would normally expect the Nicknack gene from S. simulans to be basically the same as that from D. melanogaster, because it is essential and therefore would not have changed much in the short period (in evolutionary terms) of a couple of million years. .

They tested this theory by exchanging the D. simulans gene for the D. melanogaster fly, hoping that if the genes were the same, trade would have no effect. But instead, the female files survived the exchange very well, but all the males died. Malik thinks that the difference between the sexes has to do with heterochromatin: the Y chromosome contains a lot of it.

“It’s as if the (D. Nicknack gene) from (D.) simulans enters with his hand tied behind his back,” says Malik. "It's good enough to do its job on female flies, but on male flies, where there's a huge block of heterochromatin, it can't." In other words, the gene of one species does not match its counterpart in the other.

The result suggests that in the 2.5 million years since the two species separated, D. melanogaster evolved its own version of Nicknack. And because the exchange negatively affected males, with its abundance of heterochromatin on the Y chromosome, the researchers concluded that Nicknack must play a crucial role in regulating heterochromatin. And since heterochromatin evolves so fast, the Nicknack gene also has to evolve rapidly, so it doesn’t become obsolete.

Malik then hopes to do more studies to understand the exact function of Nicknack. This may help to illuminate the role of heterochromatin in the configuration of velocity and the course of evolution. He says scientists are beginning to understand the many ways this "junk DNA" is anything but junk.

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