Sonic Hedgehog gene in snakes

The Hedgehog signaling pathway plays a role in the loss of limbs in snakes. According to the fossil record, ancestral snakes had limbs, which became reduced over the course of evolution. Some species of snakes such as boas and pythons still have a rudimentary femur and claw, while in other species such as cobras, limbs have disappeared completely. This phenotypic difference suggests that limbs were lost over time. The Sonic Hedgehog gene is regulated by a limb-specific enhancer called the zone of polarizing activity regulatory sequence (ZRS). This enhancer is conserved in all invertebrates and accounts for differences in limb development in vertebrates. A team of researchers led by a genomicist named Visel found that by substituting the ZRS of mice with the ZRS of snakes caused truncated limbs. In contrast, substituting mice with human and fish enhancers caused legs to grow normally. Sequence analysis of the ZRS in snakes showed deletions, which resulted in weak expression of Sonic Hedgehog and truncated limbs. The varying degrees of expression of Sonic Hedgehog is a possible cause of limb reduction in snakes.