This finding was strange, because DNA is a "use it or lose it" sort of tool, Menke said. In the 80 million years since snakes lost their legs, the limb-enhancing DNA should have become a mess of random mutations. The fact that these sequences were intact suggested they might serve an important function, he said.
The researchers already knew that many mammalian limb enhancers are also active during embryonic development of the external genitalia. In the new study, Menke's team used mice to find that about half of gene segments dubbed limb enhancers are also active in phallus development. After all, both limbs and phalluses are outgrowths off the main body, Menke said, so it makes sense that they'd share genes to get the job done. [8 Wild Facts About the Penis]
When looking at the Anolis lizards, the researchers found limb enhancers also affected both hind limbs and genitals. Then, they took snake enhancer sequences and spliced them into the DNA of developing mouse embryos. They found that the snake DNA segments could no longer "turn on" the genes in the mouse back legs - but they could activate the genes in the mouse genital tract. In other words, Menke said, the snake's enhancer segments have specialized to become phallus-specific.
These findings matter in part because they expand scientists' knowledge of the evolution of external genitalia. The hypothesis, Menke said, is that ancient, limbless animals reused their leg genes to develop penises when internal fertilization developed. (The penis first showed up about 310 million years ago in evolution.) These findings mesh with that notion.
The research also has implications for humans. There are genetic disorders that result in limb and genital birth defects. One example is the rare hand-foot-genital syndrome, in which people have shortened thumbs and shortened big toes, abnormalities in the wrists and ankles, and defects in the urethra and sometimes in the uterus. That syndrome is the result of a mutation in a protein-coding gene, Menke said. The new research suggests that defects in noncoding limb enhancers might cause problems, too.
The next question, Menke said, is what makes the enhancers specialized for the limbs or the genitals. Are there differences in which proteins bind to these DNA segments? Or are the differences between limbs and genitals driven by differences in the DNA segments themselves?
"Some of the circuitry has to be different," Menke said. "The morphology and function of the phallus is very different from your legs."
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