Evolutionary Backtracking

Researchers stitch two mouse genes together to recreate a gene that existed more than 500 million years ago.

By Victor Limjoco|Thursday, August 31, 2006

Scientists have reversed evolution, reconstructing an ancestral gene and demonstrating how the ancestral gene directed facial muscle development in mice.

Molecular geneticists Mario Capecchi and Petr Tvrdik worked with mice that can't close their eyes or wiggle their whiskers, similar to a human condition called Moebius Syndrome.

Turning off one gene causes the mice to lose the ability to control facial muscles. "These muscles allow you, for example, to smile or to frown or to open and close your eyelids, even to shed tears. All of the things that you normally would do with your face," Capecchi says.

This gene comes from a big family known as Hox genes, which are key to development in the embryo. Capecchi says that around 530 million years ago, early animals had 13 Hox genes, which then duplicated until animals had 52. Some of those genes mutated and became more complex, while others were eliminated due to redundancy. Today mammals, including humans, have 39 Hox genes.

Capecchi was the first scientist to reverse this process. "What we're doing is, we're recreating the same gene that existed before that gene was duplicated and then acquired completely new, different functions," he says.

One gene now controls facial muscles, while the other controls the development of the brain. By splicing these two back together in mice, Capecchi reconstructed the ancient gene that could do both. "We're going back essentially to that pre-state, back in evolution to when there was a single gene that had to do both functions," he says.

As Capecchi and Tvrdik reported in the journal Developmental Cell this ancestral gene restored the mice's ability to close their eyes. Capecchi's work advances our knowledge of evolution. "By being able to study which elements are important for this process," he says, "then we understand it in much greater detail. Here we're giving you a very concrete example and [showing] what's happening at the DNA level."

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