Mutation is the basis of phenotypic changes and serves as the source of natural selection. The development of limbs has been the milestone in vertebrate evolution. Several limb and bone-related genes were verified experimentally, but other indirect and regulatory factors of limb development remained untested, especially very few cases were observed in natural environment. We report a naturally born serpentized pig without hindlimbs. Whole genome sequencing followed by comparative genomic analysis revealed multiple interesting patterns on the handicapped pig-specific mutations. Although the bone-related genes are not directly subjected to mutations, other regulatory factors such as the RNA deaminase genes Adar are damaged in the handicapped pig, leading to the abolished A-to-I deamination in many functional, conserved genes as well as the bone-related genes. This is a precious case that the limbless phenotype is observed in naturally born non-model organisms. Our study broadened the generality of the limbless phenotype across mammals and extended the regulation of hindlimb development to other non-bone-related genes. Our knowledge of limb and bone-related mutations and regulation would also contribute to human genetics.

突变是表型变化的基础，也是自然选择的根源。四肢的发育是脊椎动物进化的里程碑。一些与肢体和骨骼相关的基因已通过实验得到验证，但肢体发育的其他间接和调节因素尚未得到测试，特别是在自然环境中观察到的情况很少。我们报道了一头天生没有后肢的蛇形猪。全基因组测序和比较基因组分析揭示了残疾猪特异性突变的多种有趣模式。尽管与骨相关的基因没有直接发生突变，但其他调节因子，例如RNA脱氨酶基因Adar在残疾猪中被破坏，导致许多功能性保守基因以及骨相关基因。这是在自然产生的非模式生物中观察到无肢表型的珍贵案例。我们的研究扩大了哺乳动物无肢表型的普遍性，并将后肢发育的调节扩展到其他非骨骼相关基因。我们对肢体和骨骼相关突变和调控的了解也将有助于人类遗传学。