When researchers at UGA examined the genomes of several snake species, they found something unexpected. Embedded in these reptiles’ genetic codes was DNA that, in most animals, controls the development and growth of limbs—a strange attribute for creatures renowned for their long legless bodies and distinctive slither.
Now, the UGA scientists have found an explanation. In a paper published in the journal Developmental Cell, they report that the genetic tools responsible for limb development also control the formation of external genitalia, which may help explain why snakes have held on to this limb circuitry through the ages.
Snakes weren’t always without legs. They evolved into limbless reptiles over 100 million years ago, said Douglas Menke, assistant professor of genetics at UGA’s Franklin College of Arts and Sciences and senior author of the paper.
“There have been many millions of snake generations since they evolved a legless body, and we would generally expect the DNA associated with limb development to fade away or mutate to do another job, but that doesn’t seem to have happened,” he said. “Naturally, we wanted to know why snakes had retained DNA that they didn’t appear to need.”
In Menke’s and postdoctoral researcher Carlos Infante’s experiments, they examined specific regions of noncoding DNA known as enhancers—“switches” that control the expression of genes, telling them when to turn on or off during embryonic development.
By following patterns of enhancer activity in embryonic limbs and genitalia of mice and lizards, the scientists observed that many of the same enhancers are activated during the formation of these appendages in both sets of species.
Menke and Infante then engineered mice that lacked one of these limb/genital enhancers, and they found defects in the legs and genitalia of the resulting mice. The snake version of this enhancer, however, only functioned during development of genitalia.
“What this meant is that much of the genetic circuitry that controls the development of limbs is also important for the formation of genitalia,” Menke said. “And we think that’s why snakes still have the genetic blueprints for limb development in their genome.”
It is generally accepted among evolutionary biologists that limbs evolved from fins, but phalluses—external genitalia that include the penis and clitoris—are thought to be a much more recent development, he said. And evidence suggests that the genes initially used to grow limbs were later co-opted for the development of a phallus.
“We’re only just beginning to understand the various roles of many of these enhancers,” Menke said. “But what we generally refer to as ‘limb enhancers’ should probably be more broadly categorized as ‘appendage enhancers’ because they clearly perform more than one job.”
The research team had access to the genomes of three snake species: boa constrictor, Burmese python and king cobra. Such comparative genomics research has only recently become possible as the genomes of snakes and other species were sequenced.
In future experiments, the Menke team plans to investigate the extent to which noncoding DNA influences the formation of different genital shapes observed in nature.
