Newspaper article The Christian Science Monitor

How Did Snakes Lose Their Legs?

Newspaper article The Christian Science Monitor

How Did Snakes Lose Their Legs?

Article excerpt

Snakes haven't always been obligate stomach slitherers. The animals' ancestors scuttled around on legs, scientists say.

And geneticists now think they know what happened.

Previously, scientists thought the change had something to do with a gene associated with limb growth across vertebrates, but the animals' genomes suggested that gene, called sonic hedgehog, hadn't been deleted. Now, two research teams have independently concluded that portions of the DNA that control the sonic hedgehog (Shh) gene had been deleted.

"The modification of small pieces of DNA can generate big changes," says biologist Francisca Leal, who conducted one of the studies.

So what happened?

Sometime after snakes and lizards diverged from their common ancestor, snakes lost their forelimbs. But tiny hindlimbs remained in the last common ancestor of all living snakes, which scientists suggest lived around 128 million years ago.

While most snakes today have no remnants of those hind legs, pythons, boas, and their relatives retain some related primitive structures. These snakes can have a pelvic girdle, the remnant of a femur and a little claw, called a spur, sticking out.

Pythons briefly develop the beginnings of limbs as embryos, and previous research had suggested the Shh gene had something to do with this flicker of limb growth.

So Ms. Leal, as a PhD candidate in Martin Cohn's lab at the University of Florida, dug into python genomes to see what was turning the gene expression off.

In the genome, short sequences of DNA called enhancers are involved in triggering gene activity. And, because Shh is involved in the development of structures other than limbs, there is a specific enhancer associated with limb development, called the ZRS, Dr. Cohn tells The Christian Science Monitor. "The only job of this short stretch of DNA is to turn on sonic hedgehog in the limb buds," he says.

Leal and Cohn found that pythons do have a ZRS, but sections of it have been deleted. And without those key pieces of the limb- specific enhancer, the proteins that bind to the DNA to kick off limb growth can't latch on.

The pair came to these conclusions, published Thursday in the journal Current Biology, by inserting the limb enhancer DNA into the genetics of a normal mouse. With this extra ZRS marked to highlight when the enhancer triggered activity, the team was able to see that the mice "showed very weak activity of the enhancer in just a few cells at a very early stage, and it's not sustained, just like in pythons," Cohn says.

Meanwhile, in California, another team was independently approaching the same problem from another angle.

Instead of simply adding a python's ZRS to normal mice, a team of researchers led by Axel Visel at the Lawrence Berkeley National Laboratory used the gene editing technology CRISPR to replace this segment of DNA in mice with those from other animals including fish, platypuses, bats, chickens, and five different kinds of snakes. …

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