Evolution in the insulin family: molecular clocks that tell the wrong time

The sequences, three-dimensional structures and biological activities of insulins and the related insulin-like growth factors demonstrate many changes that have occurred in evolution. In the hystricomorph rodent insulins this has led to insulins which differ not only from those of other mammals but also amongst themselves. They show no single characteristic substitution but generally exhibit reduced anabolic activity, increased growth promoting effects and inability to form oligomers. Their divergence is discussed in terms of orthologous evolution implying very variable rates of accepted mutations, and paralogous evolution for which a minimal hypothesis must be several silently evolving genes.