Why cows have fewer toes than you

26 June 2014

Your foot and a cow’s hoof may look very different, but 55 million years ago, both had five toes. 

Now, an international team of researchers has discovered the molecular changes that caused hoofed animals to diverge from other animals with four limbs and five toes.

The team, led by Professor Rolf Zeller from the University of Basel in Switzerland and including Associate Professor Carol Wicking from The University of Queensland’s Institute for Molecular Bioscience, identified a gene regulatory switch key to the evolution of limbs in different animals.

“The fossil record shows that all animals with four limbs originally had five toes (digits),” Dr Wicking said.

“But tens of millions of years ago, some of these animals, such as cattle, deer, giraffe and hippopotami, lost some of these toes and evolved hoofs to adapt to walking and running on different terrains.

“This study sought to discover the molecular differences that occur in limb development between animals with four limbs and five toes, and those with four limbs and hoofs, known as ungulates.”

The researchers compared the activity of genes that control the development of limbs in mouse and cattle embryos.

They found that the development of limbs in both species is initially strikingly similar, with molecular differences only becoming apparent later in development of the hand and foot plate.

The researchers found that a protein called Patched1 is not expressed in the digit-forming region in the limbs of cattle.

They subsequently identified a region of DNA that acts as a gene regulatory switch to control Patched1 expression.

In cattle embryos, and presumably other hoofed animals, the regulatory switch controlling Patched1 expression has been inactivated, meaning the signal to develop five toes isn’t received.

“The identified genetic alterations affecting this regulatory switch offer unprecedented molecular insights into how the limbs of even-toed ungulates diverged from those of other mammals roughly 55 million years ago,” Professor Zeller said.

The research was published in Nature, one of the world's top scientific journals, and supported by international agencies and Australia’s National Health and Medical Research Council.