In mammals, during embryonic development, hox genes or the ‘architect’ genes play the main role in the organizing body structures including the limbs. Hoxd gene are activated by ‘bimodal 3-dimensional DNA’ structure that directs the formation of subdivisions as arms and digits,when these genes and their expression mechanisms were compared in zebrafish and mice embryos,the results were surprising as the same biomodal 3-dimensional DNA was found in zebrafish as well. Next, the geneticists inserted the hox genes in transgenic mice embryo but again the result was unexpected, as during development the hox genes were active only in the arms and not in digits.
This study concludes that the genes for the formation of limbs were already present in fishes before the first animal walked on land about 350 million years ago, but these genes were further modified in land organisms resulting in division of arm and digits from the ancestral fins.
Our closest fish relative, the lungfishes, crawls on its four legged pointy fins. So,the transition from water to land resulted in modified genetic material thus formation of tetrapod limbs and digits which are found in nearly all land animals. Further research is needed to show what mechanisms resulted in change from fins to limbs.