Snake genomes contain DNA for limb development because those same genetic elements also control the formation of external genitalia, according to new work published in Developmental Cell.
Snakes are tetrapods just like people, dogs, and dinos. But like whales, their ancestors lost some limbs. “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," University of Georgia’s Douglas Menke said in a statement. "Naturally, we wanted to know why snakes had retained DNA that they don't appear to need."
Menke and colleagues focused on regions of noncoding DNA called enhancers, which help control the expression of genes during embryonic development. Snakes seem to have retained what appeared to be limb enhancers similar to those of mammals. "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."
Limbs evolved from fins, and there’s some evidence to suggest that genes for growing limbs were later co-opted for the development of external genitalia. Engineered mice that lack one of these limb-genital enhancers – HLEB, an enhancer of the gene Tbx4 – showed defects in their legs and genitalia.
When the researchers followed patterns of enhancer activity in the limbs and genitalia of mouse and Anolis lizard embryos, they found that the same enhancers are activated during the embryonic formation of both structures in both species.
Then they examined the genomes of three snake species: boa constrictor, Burmese python, and king cobra. While the lizard version was capable of driving gene expression in the legs and the genitalia, the snake version of this enhancer only functions during the development of genitalia. "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."
Anolis lizard embryo expression of the hindlimb/phallus gene Tbx4 (purple stain). Carlos R. Infante
Image in the text: A corn snake embryo. Carlos R. Infante