text: These experiments address various important questions in evolutionary biology: does evolution proceed in small steps or in large leaps; is evolution reversible; how does complexity evolve? It has been shown that slight mutations in the amino acid sequence of hormone receptors determine an important change in their preferences for hormones. These changes mean huge steps in the evolution of the endocrine system. Thus very small changes at the molecular level may have enormous consequences. The Thornton lab has also been able to show that evolution is irreversible studying the glucocorticoid receptor. This receptor was changed by seven mutations in a cortisol receptor, but reversing these mutations didn't give the original receptor back. Indicating that epistasis plays a major role in protein evolution – an observation that in combination with the observations of several examples of parallel evolution, support the neutral network model mentioned above. Other earlier neutral mutations acted as a ratchet and made the changes to the receptor irreversible. These different experiments on receptors show that, during their evolution, proteins are greatly differentiated and this explains how complexity may evolve. A closer look at the different ancestral hormone receptors and the various hormones shows that at the level of interaction between single amino acid residues and chemical groups of the hormones arise by very small but specific changes. Knowledge about these changes may for example lead to the synthesis of hormonal equivalents capable of mimicking or inhibiting the action of a hormone, which might open possibilities for new therapies.
  Given that ASR has revealed a tendency towards ancient thermostability and enzymatic promiscuity, ASR poses as a valuable tool for protein engineers who often desire these traits (producing effects sometimes greater than current, rationally lead tools). ASR also promises to resurrect phenotypically similar ancient organisms which in turn would allow evolutionary biochemists to probe the story of life. Proponents of ASR such as Benner state that through these and other experiments, the end of the current century will see a level of understanding in biology analogous to the one that arose in classical chemistry in the last century.