It is believed that natural selection acts on the phenotypical changes caused by mutations. Phenotypically, from fishes to amphibians to reptiles, the emergence of limbs greatly facilitates the landing of ancient vertebrates, but the causal mutations and evolutionary trajectory of this process remain unclear. We serendipitously obtained a pig of limbless phenotype. Mutations specific to this handicapped pig were identified using genome re-sequencing and comparative genomic analysis. We narrowed down the causal mutations to particular chromosomes and even several candidate genes and sites, such like a mutation-containing codon in gene BMP7 (bone morphogenetic protein) which was conserved in mammals but variable in lower vertebrates. We parsed the limbless-related mutations in the light of evolution. The limbless pig shows phenocopy of the clades before legs were evolved. Our findings might help deduce the emergence of limbs during vertebrate evolution and should be appealing to the broad community of human genetics and evolutionary biology.

中文翻译：

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自然出生的蛇化猪的比较基因组分析揭示了与四肢和骨骼发育相关的假定突变

人们认为，自然选择作用于突变引起的表型变化。从表型上看，从鱼类到两栖动物再到爬行动物，四肢的出现极大地促进了古代脊椎动物的登陆，但这一过程的因果突变和进化轨迹尚不清楚。我们偶然获得了一头无肢表型的猪。使用基因组重测序和比较基因组分析鉴定了这种残疾猪特有的突变。我们将因果突变范围缩小到特定染色体甚至几个候选基因和位点，例如基因 BMP7（骨形态发生蛋白）中含有突变的密码子，该基因在哺乳动物中是保守的，但在低等脊椎动物中是可变的。我们根据进化分析了与无肢相关的突变。无肢猪在腿进化之前显示出进化枝的表型。我们的发现可能有助于推断脊椎动物进化过程中四肢的出现，并且应该吸引人类遗传学和进化生物学的广泛社区。